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Biomedical subjects

J Blair

Publications and source records attributed to J Blair.

At least 19 recordsLinked to original sources

The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E.

Cyclin E is required for S phase entry. The subsequent ubiquitin-dependent degradation of cyclin E contributes to an orderly progression of the S phase. It has been shown that phosphorylation of threonine 380 (Thr380) in cyclin E provides a signal for its ubiquitin-dependent proteolysis. We report that SKP2, an F-box protein and a substrate-targeting component of the SCF(SKP2) ubiquitin E3 ligase complex, mediates cyclin E degradation. In vitro, SKP2 specifically interacted with the cyclin E peptide containing the phosphorylated-Thr380 but not with a cognate nonphosphorylated peptide. In vivo, expression of SKP2 induced cyclin E polyubiquitination and degradation. Conversion of Thr380 into nonphosphorylatable amino acids caused significant resistance of cyclin E to SKP2. The presence of the CDK inhibitor p27(Kip1) also prevented the SKP2-dependent degradation of cyclin E. Our findings suggest that SKP2 regulates cyclin E stability, thus contributing to the control of S phase progression.

Amino Acid Sequence↗

Phenotype, ovarian function, and growth in patients with 45,X/47,XXX Turner mosaicism: implications for prenatal counseling and estrogen therapy at puberty.

OBJECTIVE: Our objective was to determine whether girls with the rare Tur-ner 45,X/47,XXX mosaic karyotype are less severely affected than girls with 2 commoner karyotypes. STUDY DESIGN: We evaluated growth status, phenotype, and ovarian function in 7 girls with 45,X/47,XXX mosaicism, age-matching each with 2 girls with 45,X and 1 with 45,X/46,Xi(X)(q10) karyotypes. RESULTS: For the index, 45,X, and 45,X/46,Xi(X)(q10) groups, respectively, the median/mean height SD score at the start of growth hormone therapy/comparable age was -2.0 (-1.2), -2.3 (-2.4), and -2.6 (-2.6), cardiac anomalies were identified in 0 of 7, 4 of 14, and 1 of 7, renal abnormalities in 0 of 7, 4 of 14, and 3 of 7, middle ear problems in 2 of 7, 11 of 14, and 4 of 7, and special educational needs in 0 of 7, 3 of 14, and 1 of 7. Complete spontaneous puberty with menarche was seen in all but 1 girl older than 12 years in the index group compared with only 1 girl in the comparison groups. Ovarian tissue was identified in 6 of 7, 0 of 14, and 1 of 7 girls, and the mean follicle-stimulating hormone was 6, 25, and 21 U/L, respectively. CONCLUSION: Girls with 45,X/47,XXX karyotype are mildly affected, with good preservation of ovarian function. This result has important implications for prenatal counseling and the need for estrogen therapy at puberty.

Adolescent↗

The continuing HIV epidemic among men who have sex with men.

OBJECTIVES: This study characterized the AIDS epidemic among urban men who have sex with men (MSM). METHODS: A probability sample of MSM was obtained in 1997 (n = 2881; 18 years and older) from New York, Los Angeles, Chicago, and San Francisco, and HIV status was determined through self-report and biological measures. RESULTS: HIV prevalence was 17% (95% confidence interval = 15%, 19%) overall, with extremely high levels in African Americans (29%), MSM who used injection drugs (40%), "ultraheavy" noninjection drug users (32%), and less educated men (< high school, 37%). City-level HIV differences were non-significant once these other factors were controlled for. In comparing the present findings with historical data based on public records and modeling, HIV prevalence appears to have declined as a result of high mortality (69%) and stable, but high, incidence rates (1%-2%). CONCLUSIONS: Although the findings suggest that HIV prevalence has declined significantly from the mid-1980s, current levels among urban MSM in the United States approximate those of sub-Saharan countries (e.g., 14%-25%) and are extremely high in many population subsegments. Despite years of progress, the AIDS epidemic continues unabated among subsegments of the MSM community.

Adolescent↗

Magnetic resonance imaging of the temporomandibular joint.

The spectrum of disease that affects the temporomandibular joint (TMJ) can be varied. To differentiate among the diseases that cause pain and dysfunction, an intimate knowledge of the anatomy, physiology, and pathology of this region is necessary. Due to the joint's complex anatomy and relationship to the skin, it has been difficult to image in the past. Magnetic resonance imaging is ideally suited for visualizing TMJ because of its superb contrast resolution when imaging soft tissues. Magnetic resonance imaging allows simultaneous bilateral visualization of both joints. The ability to noninvasively resolve anatomic detail can be performed easily and quickly using magnetic resonance imaging. The development of magnetic resonance imaging has greatly aided the diagnosis of TMJ disorders. An understanding of TMJ anatomy and pathogenesis of TMJ pain is crucial for interpretation of magnetic resonance imaging and subsequent treatment.

Humans↗

Comparison of three isolation systems for the culture of mycobacteria from respiratory and non-respiratory samples.

AIMS: To compare the recovery of mycobacteria from clinical samples using the MB/BacT rapid culture system with that obtained using egg medium or the Bactec radiometric method. METHODS: The three methods were compared using 681 clinical samples (462 respiratory and 219 non-respiratory samples) and eight external quality control strains. Culture media were incubated at 35-37 degrees C for six weeks in the MB/BacT system and for 12 weeks in the Bactec system and on egg medium. Solid media were examined macroscopically once a week and the Bactec vials were read six times in the first two weeks, and then weekly for the next 10 weeks (a growth index > 50 indicated a positive vial). The MB/BacT system positive vials were unloaded from the machine as soon as possible after detection. Confirmation of growth for all systems was by Ziehl-Neelson stained smears. Isolates were identified by a combination of phenotypic and molecular methods. RESULTS: Of the 681 clinical samples, 59 (8.7%) were positive on culture, including 23 strains of Mycobacterium tuberculosis. None of the three systems recovered all of the isolates, but each recovered mycobacteria not detected by either of the other two systems. After six weeks incubation, isolation rates were 87%, 78%, and 90%, and mean times to detection were 13, 19, and nine days for the MB/BacT, egg medium, and Bactec systems, respectively. Although the MB/BacT system was slightly slower than the Bactec system, the biomass was greater, allowing earlier use of molecular probes and earlier inoculation of susceptibility tests. CONCLUSIONS: The MB/BacT system provides comparable performance to the Bactec radiometric system, without the problems of disposal of radioactive waste. Optimal recovery is obtained when culture on egg medium is used in conjunction with a rapid culture system.

Bacteriological Techniques↗

Fractionation of visual memory: evidence from a case with multiple neurodevelopmental impairments.

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. However, it is unclear whether these cognitive subsystems can fractionate developmentally. The present study describes an investigation of visual memory of a patient (PE) with multiple developmental disorders. PE was congenitally deaf, had Gilles de la Tourette syndrome and autism, with non-verbal ability in the normal range. The patient presented with a recognition memory impairment for unknown human faces. This contrasted with his superior recognition memory for unknown buildings, landscapes and outdoor scenes. PE's memory impairment for faces could not be explained by a general deficit in face processing. Interestingly, PE also showed a recognition memory impairment for animals. These findings indicate that different domains of the visual memory system can be fractionated developmentally. In particular, it demonstrates that topographical memory can develop independently from other aspects of visual memory.

Adult↗

Dynamic aphasia: an inability to select between competing verbal responses?

In this study we report a patient (A.N.G.) who, following a malignant left frontal meningioma impinging upon Brodmann area 45, presented a 'pure' dynamic aphasia. Her spontaneous speech was markedly reduced in the absence of any syntactical impairment. Her naming, repetition and reading skills were completely normal. Two experimental investigations were carried out. The first investigation found that A.N.G. had a profound impairment in phrase and sentence generation tasks given a verbal context. However, her verbal generative skills were normal when she was asked to describe pictorial scenes and complex actions. Moreover, it was found that A.N.G. had no difficulty ordering the constituent words of a sentence. Thus, it was concluded that her verbal planning skills were intact. The second investigation tested a hypothesis that dynamic aphasia is due to an inability to select a verbal response option whenever the stimulus activates many competing verbal responses. Predictions based upon this hypothesis were confirmed on three different verbal generation tasks. It was found that our patient's grave verbal generative impairment was present for tasks involving stimuli which activate many potential responses. However, it was absent for tasks involving stimuli which activate few or only a single 'prepotent' response. The findings are discussed with reference to traditional interpretations of dynamic aphasia and more general interpretations of prefrontal cortex functioning. On the basis of a computational model of prefrontal cortex functioning, we propose that pure dynamic aphasia may be caused by damage to a 'context' module containing units responsible for selection of verbal response options. Moreover, it is suggested that our findings support the view that Brodmann area 45 is involved in verbal response generation to stimuli which activate many potential response options.

Aphasia↗

Acute effects of ambient inhalable particles in asthmatic and nonasthmatic children.

Although increases in inhalable particle (PM10) concentrations have been associated with acute reductions in the level of lung function and increased symptom reporting in children, including children with asthma, it is not clear whether these effects occur largely in asthmatic children, or even whether asthmatic children are more likely to experience these effects than children without asthma. To address these points, the following subgroups of children were selected from a survey population of all 2,200 elementary school children (6 to 13 yr of age) in a pulp mill community on the west coast of Vancouver Island: (1) all children with physician-diagnosed asthma (n = 75 participated), (2) all children with an exercise-induced fall in FEV1 without diagnosed asthma (n = 57), (3) all children with airway obstruction (FEV1/FVC < 0.76) without either of the above (n = 18), and (4) control children without any of the above (n = 56). The children were followed for as long as 18 mo with twice daily measurements of peak expiratory flow (PEF) and daily symptom diary recording. Maximum daily PM10 concentration was 159 microm/m3 (median, 22.1), but only 8 d (1.2%) had concentrations above 100 microg/m3. In an analysis that accounted for time-varying covariates, and serially correlated and missing data, for the entire sample of children, increases in PM10 were associated with reductions in PEF and increased reporting of cough, phlegm production, and sore throat. For the subgroup of children with diagnosed asthma, PEF in the time period with the highest PM10 concentrations fell by an estimated 0.55 L/min (95% CI, 0.06 to 1.05) for a 10 microg/m3 PM10 increase above the mean daily PM10 concentration of 27.3 microg/m3 and the odds of reported cough increased by 8% (95% CI, 0 to 16%); no consistent effects were observed in the other groups of children. It is concluded that children experience reductions in PEF and increased symptoms after increases in relatively low ambient PM10 concentrations, and that children with diagnosed asthma are more susceptible to these effects than are other children.

Adolescent↗

Electrical injury from subway third rails: serious injury associated with intermediate voltage contact.

BACKGROUND: Railway and subway-associated electrical trauma is rare and typically involves high voltage (> 20,000) arc injuries. Not all rail systems utilize such high voltage. We report 16 cases of electrical trauma due to 600 V direct contact with subway 'third' rails. METHODS: A case series of injured patients presenting to Shriners Burns Institute, Boston or Massachusetts General Hospital between 1970 and 1995 was retrospectively analyzed. RESULTS: A total of 16 cases was identified. Among seven subway workers, the mechanism of rail contact was unintentional by a tool, a hand or by falling; no deaths occurred. Among nine non-occupational victims, injuries involved suicide attempts, unintentional falls, or risk-taking behavior. This group suffered greater burn severity, operative procedures, and complications; three deaths occurred. CONCLUSIONS: This is the largest report series of direct electrical trauma from a subway third rail. The high morbidity and mortality from this 600 V contact suggests that the traditional classification of low voltage (< 1000 V) exposure can be subdivided to reflect the serious and lethal potential of intermediate range exposures compared to household range exposures (0-220 V).

Accidents↗

Ileal pouch-anal anastomosis: pregnancy, delivery and pouch function.

OBJECTIVE: To evaluate the pregnancies, deliveries and functional results of patients who have undergone and ileal pouch-anal anastomosis. DESIGN: A retrospective survey by questionnaire. SETTING: The study was conducted at a university hospital. SUBJECTS: Twelve women who had undergone an ileal pouch-anal anastomosis at the Inflammatory Bowel Disease Centre, Mount Sinai Hospital and who had subsequently become pregnant, were identified from the hospital records. A follow up questionnaire was completed by all subjects. RESULTS: Twelve patients had 16 deliveries. There were 10 vaginal deliveries and 6 caesarian sections. There were no pouch-related complication during the 16 pregnancies and there were two postpartum complications. CONCLUSIONS: Pregnancy is safe in women with an ileal pouch-anal anastomosis. Functional results are altered minimally. Vaginal delivery is safe and obstetric reasons should determine whether a caesarian section is performed.

Adolescent↗

Effect of ambient ozone exposure on lung function in farm workers.

Effects of ozone exposure on outdoor farm workers in the Fraser Valley of British Columbia, Canada, were investigated. Fifty-eight workers underwent spirometry daily before and after each 8- to 14-h workday from June 23 to August 26, 1993. The mean daily maximum (1 h) ambient ozone concentration was 40 ppb (range: 13 to 84 ppb). Concentrations of acid aerosols and fine particulates, potential confounders of ozone effects, were very low. In individual regressions of evening FEV1 and FVC on maximum daily ozone concentration, 47 of 53 workers with valid data (46 of 53 for FVC) had negative slopes. The average slopes (weighted by the inverse SE of the regression coefficients) were -3.3 and -4.7 ml for FEV1 and FVC, respectively, for each ppb increase in ozone (p < 0.001). Following correction for an individual's mean lung function level, date, and temperature, regression of either the afternoon or the daily change (afternoon-morning) corrected for the morning measurement of FEV1 and FVC on ozone showed similar magnitudes of effect. These associations were still apparent on the following morning, suggesting a persistent ozone effect. These results indicate that exposure of a population of outdoor workers to ambient ozone concentrations below 85 ppb is associated with decreased lung function over the day, which persists to the following day.

Adult↗

Calcium pyrophosphate dihydrate deposition disease presenting as tumoral calcinosis (periarticular pseudogout).

It has been considered unusual for periarticular calcifications to consist of calcium pyrophosphate dihydrate (CPPD). We describe a patient presenting with pain and inflammation adjacent to the site of tumoral calcifications and extending to the first metatarsophalangeal joint. Aspiration of the material revealed weakly positive birefringent rhomboid shaped crystals that proved to be CPPD by atomic force microscopy. The patient had no metabolic abnormalities or radiographic chondrocalcinosis. We believe other cases similar to ours represent another clinical form of CPPD deposition disease-periarticular pseudogout.

Aged↗

Emergency management of major hydrofluoric acid exposures.

Exposures of as little as 2.5 per cent of the body surface to concentrated hydrofluoric acid (HF) may be fatal. Survival after major HF exposures is facilitated by aggressive emergency management which, we feel, includes wound irrigation, subeschar injection of calcium gluconate, monitored supplementation of serum calcium, and prompt wound excision carried out as an emergency procedure. The following case reports and literature review illustrate the important differences between exposures to concentrated HF of as little as 2 per cent of the body surface and smaller exposures to concentrated HF or exposure to dilute HF.

Accidents, Occupational↗