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J Smith

Publications and source records attributed to J Smith.

At least 361 records · Page 20Linked to original sources
PubMed1998

Abnormal rearrangements associated with V(D)J recombination in Fanconi anemia.

The hallmark of Fanconi anemia (FA), a rare inherited cancer prone disorder, is a high level of chromosome breakage, spontaneous and induced by cross-linking agents. The increased genomic instability of FA is reflected at the gene level by an overproduction of intragenic deletions. Two of the eight FA genes have been cloned, however, their function remains unknown. We recently demonstrated that the lack of functional FA genes lead to a marked decrease in the fidelity of non-homologous end-joining, a pathway that mammalian cells predominantly use to repair DNA double-strand breaks (DSB). Knowing that specific DSB are generated during V(D)J recombination, here we have examined the molecular features of V(D)J rearrangements in normal and FA lymphoblasts belonging to complementation groups C and D. Using appropriate extrachromosomal recombination substrates, V(D)J coding and signal joint formation have been analysed quantitatively and qualitatively. Our results show that the frequency of coding and signal joint formation was not significantly different in normal and FA cells. However, when the fidelity of the V(D)J reaction was examined, we found that in normal human lymphoblasts V(D)J recombination proceeds with high precision, whereas, in FA cells a several fold increase in the frequency of aberrant rearrangements is associated with V(D)J coding joint formation. The abnormal recombinants that we recovered in FA are consistent with excessive degradation of DNA ends generated during the V(D)J reaction. On the basis of these findings, we propose a working model in which FA genes play a role in the control of the fidelity of rejoining of specific DNA ends. Such a defect may explain several basic features of FA, such as chromosomal instability and deletion proneness.

Cell Line↗
PubMed1998

Laboratory test differences associated with HTLV-I and HTLV-II infection. Retrovirus Epidemiology Donor Study Investigators.

Reports of laboratory abnormalities associated with HTLV-I and HTLV-II infection are inconsistent. We assessed complete blood counts and selected serum chemistry measures at enrollment in a cohort of 153 HTLV-I-seropositive, 386 HTLV-II-seropositive, and 795 HTLV-seronegative blood donors. Linear and logistic regression were used to adjust for potential confounding variables including age, gender, race/ethnicity, education level, blood center, and injection drug use. Compared with seronegative donors, absolute lymphocyte counts were 6% and 10% higher, on average, in HTLV-I-infected (p = .03) and HTLV-II-infected (p = .0001) donors, respectively. HTLV-I- and HTLV-II-seropositive donors had, on average, 17,630 (p = .003) and 15,160 (p = .0005) more platelets, respectively. HTLV-I-infected donors also had an average of 30 fewer eosinophils/microl (p = .003) and a slightly higher level of lactic dehydrogenase (p = .05). HTLV-II-infected subjects had on average, an 11% decrease in creatine kinase (p = .006), a minor increase in mean corpuscular volume (p = .01), and a slightly lower serum calcium level (p = .0005). These results indicate that both HTLV-I and HTLV-II may raise levels of lymphocytes and platelets by unknown mechanisms. Lower eosinophil counts may be related to the increased susceptibility of HTLV-I-infected subjects to parasitic diseases.

Adult↗
PubMed1998

Kinetic tuning of myosin via a flexible loop adjacent to the nucleotide binding pocket.

A surface loop (25/50-kDa loop) near the nucleotide pocket of myosin has been proposed to be an important element in determining the rate of ADP release from myosin, and as a consequence, the rate of actin-myosin filament sliding (Spudich, J. A. (1991) Nature 372, 515-518). To test this hypothesis, loops derived from different myosin II isoforms that display a range of actin filament sliding velocities were inserted into a smooth muscle myosin backbone. Chimeric myosins were produced by baculovirus/Sf9 cell expression. Although the nature of this loop affected the rate of ADP release (up to 9-fold), in vitro motility (2.7-fold), and the Vmax of actin-activated ATPase activity (up to 2-fold), the properties of each chimera did not correlate with the relative speed of the myosin from which the loop was derived. Rather, the rate of ADP release was a function of loop size/flexibility with the larger loops giving faster rates of ADP release. The rate of actin filament translocation was altered by the rate of ADP release, but was not solely determined by it. Through a combination of solute quenching and transient fluorescence measurements, it is concluded that, as the loop gets smaller, access to the nucleotide pocket is more restricted, ATP binding becomes less favored, and ADP binding becomes more favored. In addition, the rate of ATP hydrolysis is slowed.

Actins↗
PubMed1998

Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud's syndrome.

Mazabraud's syndrome, though uncommon, is reported increasingly frequently. It represents an entity readily recognisable radiologically on MR imaging. Awareness of the syndrome, particularly when the myxoma is solitary, can prevent misdiagnosis of intramuscular myxomas (especially when large) as malignant mesenchymal tumors containing myxoid tissue. We review the 34 cases previously reported in the literature and include a recent case from our center.

Adult↗
PubMed1998

Response to bronchodilators in clinically stable 1-year-old patients with bronchopulmonary dysplasia.

UNLABELLED: Bronchodilators are often used in the treatment of patients with bronchopulmonary dysplasia (BPD). However, few studies evaluate their efficacy in patients with stable disease beyond the newborn period. Therefore, pulmonary function was measured before and after aerosol treatment with salbutamol (0.25 ml Ventolin 0.5%) and subsequently after aerosol with ipratropium bromide (0.25 ml Atrovent 0.025%). Studies were performed at the corrected postnatal age of 52 +/- 2 weeks in 52 patients who had been ventilated after birth because of newborn lung disease. Twenty-two of these 52 patients had developed BPD. Pulmonary function was measured after sedation and using the PEDS system. Expiratory resistance (median 52.1 versus 39.1 cmH2O/l/s; P < .008) and inspiratory resistance (median 42.5 vs 27.8 cmH2O/l/s; P < .04) were significantly worse in BPD patients at the age of 1 year. Half of the BPD patients had a decrease in pulmonary resistance after salbutamol. However, there was no statistically significant decrease in pulmonary resistance after salbutamol or ipratropium in the BPD patients as a group. After salbutamol pulmonary resistance significantly worsened in the patients who did not develop BPD. CONCLUSION: Although individual patients may benefit, routine administration of bronchodilators seems not warranted in stable BPD patients at the age of 1 year.

Administration, Inhalation↗
PubMed1998

The preparticipation physical examination: Mayo Clinic experience with 2,739 examinations.

OBJECTIVE: To report the results of preparticipation physical examination (PPE) performed on 2,739 high school athletes and present a model for providing PPEs in similar practice settings. DESIGN: We analyzed 2,739 PPEs performed on high school athletes by means of a station examination approach in our Sports Medicine Center during a 3-year period. MATERIAL AND METHODS: Personnel from the Departments of Physical Medicine and Rehabilitation, Orthopedics, Family Medicine, and Internal Medicine participated in performance of a comprehensive station-based physical examination of high school athletes. The final reviewing physician assigned one of three dispositions to each athlete: cleared for participation in sports, not cleared, or cleared with follow-up recommended. RESULTS: On the basis of PPE findings, 53 athletes (1.9%) were disqualified from participation in sports. Abnormalities that did not preclude participation but necessitated follow-up were identified in another 327 athletes (11.9%). Musculoskeletal problems were the leading cause of restriction from sports activities (43.4%) and the second leading cause for recommended follow-up (27.8%). Clinically significant cardiac abnormalities were noted in only 10 athletes (0.37% of the overall group of students). Our methods and results are discussed in relationship to previous PPE studies. CONCLUSION: On the basis of this study, we conclude that (1) a Sports Medicine Clinic can efficiently administer PPEs to a large number of athletes by using an adaptable station approach, (2) the musculoskeletal component of a PPE is an important part of the process that often reveals abnormalities and should be performed by qualified personnel, and (3) each practice must refine its delivery of PPEs on the basis of its particular environment.

Adolescent↗
PubMed1998

Leuprolide acetate (30-mg depot every four months) in the treatment of advanced prostate cancer.

OBJECTIVES: An unblinded, multicenter study to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide (30 mg injected intramuscularly every 16 weeks) was carried out in 49 patients with Stage D2 prostate cancer. METHODS: Clinical evaluations were performed every 16 weeks, and serum testosterone levels were monitored biweekly or weekly for 32 weeks. RESULTS: The mean serum testosterone level for the 45 evaluable patients fell to the castrate range (50 ng/dL or less) by week 3 after the initial depot injection and remained at that level throughout the initial 32-week treatment period. The median time to the onset of castrate levels was 22 days (range 9 to 43). Onset of castrate levels of testosterone was achieved within 4 weeks of the initial depot injection in 96% of patients. One patient (2%) experienced a transient "escape" (testosterone levels greater than 50 ng/dL on two consecutive determinations). Delay of an injection by up to 3 weeks did not have an effect on testosterone suppression. Objective tumor response (no progression) occurred in 90% of patients at week 16 and in 80% at week 32. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more at week 32 in 97% and 76% of patients, respectively. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (45%), back pain (16%), and arthralgia (14%). CONCLUSIONS: The 30-mg depot formulation of leuprolide, which acts in a manner similar to the 7.5- and 22.5-mg depot formulations (given monthly and every 3 months, respectively) is effective in lowering serum testosterone to castrate levels in all patients and demonstrates a favorable response in 80% of the patients with advanced prostate cancer for the 32-week observation period. The drug was well tolerated in all patients.

Acid Phosphatase↗
PubMed1998

Results of a multicenter trial of the CapSure (Re/Stor) Continence shield on women with stress urinary incontinence.

OBJECTIVES: To prospectively study the impact of the CapSure (Re/Stor) Continence shield for the treatment of stress urinary incontinence. METHODS: One hundred women with pure stress urinary incontinence were enrolled in a 6-month study. Objective measures of urine loss included pad weight test (PdWt) and provocative stress test (PST). Subjective measures included incontinence diaries documenting the number of incontinence episodes per day (IEPD), quality of life questionnaires, and satisfaction surveys. Objective and subjective measures were performed prior to enrollment, during use of the CapSure shield, and after discontinuation of the device. RESULTS: During the 12-week device utilization period, PdWt measurements demonstrated a 96% reduction in urine loss by week 1 and 97% by week 12. Eighty-two percent of subjects were completely dry by week 12. PST demonstrated 100% reduction in urine loss at each visit, with 91% of subjects completely dry by week 12. IEPD also demonstrated a 91% reduction in incontinence episodes by week 12. Quality of life scores and patient satisfaction surveys demonstrated significant improvement. During the 6-week post device utilization period (PUP), subjects continued to demonstrate a reduction in urine loss compared to pre-enrollment data, despite discontinuation of use. PdWt measurements demonstrated a 73% and 79% reduction in urine loss at weeks 14 and 18, respectively. Measurements of PST and IEPD demonstrated significant reductions in urine loss at weeks 14 and 18. A 1.5% prevalence of positive urine cultures was noted during device use. Bothersome vaginal or urethral irritation occurred in 12% of patients. Adverse events were few and required no therapeutic intervention. CONCLUSIONS: The CapSure shield is a safe and efficacious method of managing stress urinary incontinence in women.

Adult↗
PubMed1998

Persistently poor outcomes of undetected major depression in primary care.

Despite its relevance for quality care initiatives, the field of psychiatry has little scientific knowledge regarding the course of current major depression when primary care patients with the disorder remain undetected. Using statewide telephone screening, we identified and followed 98 adults with current major depression who made one or more visits to a primary care physician during the 6 months following baseline. Thirty-two percent of primary care patients with current major depression remained undetected for up to 1 year. Almost half of undetected patients developed suicidal ideation. Less than one-third of undetected patients made a visit during the month they reported their worst symptoms. Fifty-three percent of undetected patients reported five or more current symptoms at 1 year follow-up. Primary care patients with undetected major depression report persistently poor outcomes. Comparison of outcomes with detected patients suggests that quality improvement efforts directed at improving detection without improving management of detected patients may not improve outcomes.

Adult↗
PubMed1998

Randomized study of carotid angioplasty and stenting versus carotid endarterectomy: a stopped trial.

BACKGROUND: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease. METHODS: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days. RESULTS: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days. CONCLUSIONS: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.

Aged↗
PubMed1998

A census-based design for the recruitment of a community sample of older adults: efficacy and costs.

PURPOSE: This is a report of the scientific and cost implications of a census-based design to identify residents aged 55 and over for a community study of the effects of aging on physical function. METHODS: A census of residents in a study community was conducted by the use of a mailed questionnaire. For households that did not complete and return the mailed census questionnaire, contact was attempted first by telephone and then by home visit. A comparison was made of the unit costs and characteristics of subjects identified by the different methods. RESULTS: A total of 3509 age-eligible subjects were identified (78.3% by mailer, 19.5% by telephone, and 2.0% by home visit). Costs per enrolled age-eligible subject were lower for mailing and telephone ($7.76 and $4.72 respectively) than for home visit ($36.25). Subjects identified by home visit were significantly younger than subjects identified either by mail or telephone. After adjustment for age, subjects identified by telephone had less education and income and poorer health and functional status than subjects identified by mail. With the exception of age, there were no significant differences between subjects identified by mailer and home visit. CONCLUSIONS: A mailed questionnaire with telephone recontact is a practical strategy for community-based recruitment. Recontact of subjects by telephone can be expected to identify subjects who are not well-represented in a sample based only on a mailer. In contrast, the home visit is expensive and identifies subjects who do not differ meaningfully from those identified by mailer.

Aged↗
PubMed1998

Certifying the elimination of poliomyelitis from Europe: advancing towards global eradication.

UNLABELLED: Indigenous wild polioviruses have been virtually eliminated from the 51 countries of the European Region of the World Health Organization (WHO), an achievement that is of critical importance to the global initiative to eradicate poliomyelitis by the year 2000. An international commission has been established to certify the elimination of poliomyelitis from this region. European countries have recently been requested to establish National Certification Committees to review and submit the necessary documentation and surveillance data. In some Western European countries where polio has not been reported for many years, the challenge will be to produce robust evidence demonstrating both the current absence of wild poliovirus and the means to promptly detect and respond to possible importations of wild poliovirus for the next several years, up to global eradication and the cessation of polio vaccination. KEY MESSAGES: 1. laboratory-based surveillance with collection of faecal specimens is necessary to demonstrate the absence of indigenous wild poliovirus 2. certification can only occur after all countries have demonstrated the absence of indigenous wild polioviruses for at least 3 years and have the means to detect and respond to importations of wild poliovirus for several years into the future 3. any single case of poliomyelitis in Europe now requires an immediate public health response which includes virological investigation and prompt notification to the World Health Organization.

Certification↗
PubMed1998

The role of gender in very old age: profiles of functioning and everyday life patterns.

Older men and women have different life contexts as a function of differential longevity and socio-structural opportunities over the life course. The question is whether gender-related differences also occur in psychological and everyday functioning in older adults. Examined were 258 men and 258 women between the ages of 70 and 103 years (M = 85 years), participants in the Berlin Aging Study. Significant gender differences were observed in 13 of 28 aspects of personality, social relationships, everyday activity patterns, and reported well-being. Cluster analysis identified 11 subgroups whose profiles of life conditions and health and psychological functioning could be categorized as more or less desirable (functional). The relative risk of a less desirable profile was 1.6 times higher for women than for men. For older adults, gender as a variable carries differences in physical frailty and life conditions that likely have consequences for psychological functioning.

Activities of Daily Living↗
PubMed1998

Evidence for a prostate cancer susceptibility locus on the X chromosome.

Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.

Adult↗