Biomedical subjects
Publications and source records attributed to A Smith.
We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.
We report the first observation of exclusive decays of the type B-->D(*)N_NX, where N is a nucleon. Using a sample of 9.7x10(6)B_B pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B0-->D(*-)p_p pi(+)) = (6.5(+1.3)(-1.2)+/-1.0)x10(-4) and B(B0-->D(*-)p_n) = (14.5(+3.4)(-3.0)+/-2.7)x10(-4). Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.
We analyze 9.7x10(6) B_B pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Upsilon(4S) resonance. We measure the rates for B0-->J/psiK((*)0) and B+-->J/psiK((*)+) decays and use the world-average B-meson lifetime ratio to extract the relative widths f(+-) / f(00) = gamma(Upsilon(4S)-->B+B-) / gamma(Upsilon(4S)-->B0 B-0)) = 1.04+/-0.07(stat)+/-0.04(syst). With the assumption that f(+-)+f(00) = 1, we obtain f(00) = 0.49+/-0.02(stat)+/-0.01(syst) and f(+-) = 0.51+/-0.02(stat)+/-0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Upsilon(4S) resonance.
OBJECTIVES: The aims of the present study were first to investigate the dietary intake pattern of UK teenagers and secondly to determine the relationship, if any, between dental erosion and dietary intake in these children. METHODS: The study group consisted of a cluster random sample of 14-year-old school children in Birmingham, UK: 418 children were examined from 12 different schools; 209 were male and 209 female. Data on the rate and frequency of consumption of drinks, foods, and fruits were obtained from a self-reported questionnaire supplemented by a structured interview. The data were analysed using SPSS with Chi-square, and Spearman correlation analysis. RESULTS: Over 80% of the teenagers regularly consumed soft drinks but approximately half of these children had a relatively low weekly consumption. However, 13% and 10% respectively had more than 22 intakes per week of cola and other carbonated drinks. Almost a quarter of these 14-year-olds had alcoholic drinks, with significantly more males than females involved (Chi-square P < 0.05) . Girls had a greater intake of fruits. Statistically significant correlations were found between the prevalence of erosion and the consumption of soft drinks, carbonated beverages, alcohol drinks, fresh fruits, Vitamin-C tablets and foodstuffs (Spearman correlation analysis P < 0.05). CONCLUSION: It was concluded that consumption particularly of soft drinks was high and common in teenage school children in Birmingham, UK. In addition there was a relationship between dental erosion and acidic dietary intake. Further investigation of the erosive potential of these drinks and foods is required.
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Pulmonary infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) causes a chronic destructive bronchitis. A xenograft model was used to study the susceptibility of the CF respiratory epithelium to P. aeruginosa strain PAK and the virulence of certain mutants. Despite an early trend toward increased susceptibility, colonization of CF xenografts (ID(95), 62 colony-forming units [cfu]) was not statistically different (P=.5) than in xenografts with normal respiratory cells (ID(95), 1.2x10(3) cfu). Infection severity in 12 CF xenografts (mean polymorphonuclear leukocyte [PMNL] density, 1.88x10(6)+/-1.75x10(6)/xenograft) was similar to that in 16 non-CF xenografts (3.19x10(6)+/-2.45x10(6) PMNL/xenograft; P=.38), despite slightly greater bacterial density in the CF xenografts (mean, 1.57+/-2.73x10(6) cfu/xenograft) versus xenografts with normal epithelium (mean, 1.03+/-1.3x10(6) cfu/xenograft). P. aeruginosa mutants pilA and fliF, but not rpoN, colonized normal respiratory xenografts, indicating that colonization and infection in this model depend on an uncharacterized RpoN-controlled gene. This model appears to be suitable for genetic study of P. aeruginosa virulence but not of the CF respiratory tract's unique susceptibility.
Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.
OBJECTIVES: To establish the prevalence of erosion in a cluster random sample of 14- year-olds in Birmingham UK. To determine whether socioeconomic group influences the prevalence of erosion. METHODS: The study group consisted of a cluster random sample of 14-year-old school children in Birmingham UK: 418 children were examined from 12 different schools; 209 were male and 209 female. The level of tooth wear was recorded using a modification of the (TWI) index of Smith and Knight (1984). The ACORN classification was used to assess the socioeconomic status of all children. RESULTS: Results showed that 48% of the children had low erosion, 51% had moderate erosion and only 1% had severe erosion. There were statistically significant differences between males and females; more males had buccal/labial and lingual/palatal tooth surface erosion than females (Chi-square analysis P < 0.001). There was also significantly more erosion observed in teenagers in the lowest socioeconomic categories. CONCLUSION: It was concluded that moderate levels of dental erosion are common in 14-year-old school children and this may lead to increasing clinical problems. There was significantly more erosion in children from low socioeconomic groups. Possible aetiological factors need to be investigated further.
The t(1;19)(q23;p13) has been reported in up to 6% of cytogenetically abnormal cases of acute lymphoblastic leukaemia (ALL), associated with a pre-B-ALL phenotype. In the 5-year period 1995-1999, we detected t(1;19) in 13 children and 2 adults with newly diagnosed ALL. This represented 10% of pediatric and 2.5% of adult diagnostic ALL samples successfully cultured in one center during this time. There were 9 males and 6 females. The mean age at diagnosis for the 13 children was 6.5 years (range 1.5 to 14 years) and the 2 adults were aged 42 and 45 years. The unbalanced t(1;19) occurred in 7 of 13 children (54%), contrary to the reported excess of unbalanced translocations at 75%; both adults had the unbalanced translocation. At diagnosis, the t(1;19) was the sole abnormality in 4 patients (26%), and in the remainder (74%) was part of a complex karyotype, which included i(7q) (2 patients), hyperdiploidy (2 patients) and del(6q) (2 patients). Correlation of karyotype with white cell, blast and platelet counts, cell surface markers, initial response to chemotherapy and short-term outcome showed no difference between the balanced and unbalanced forms of the translocation in children or whether t(1;19) was present as the sole abnormality or part of a complex karyotype.
BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.
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In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).
The segregation of the rhombencephalic neural crest into three streams, destined for particular pharyngeal arches, is a prominent feature of the developing vertebrate head and is likely necessary for normal morphogenesis. At least in part, the segregation of the crest into these streams involves the focal depletion of neural crest from rhombomeres 3 and 5 through large-scale apoptosis, mediated by the induction of Bmp-4 expression in the crest primordia of these two rhombomeres. Previously we found that in contrast to rhombomeres 3 and 5, the intervening segment rhombomere 4 was not susceptible to Bmp-4-sponsored neural crest cell death. To analyse the reason for this difference, we have isolated clones for the necessary components of the Bmp-4 signal transduction apparatus. We find that the hindbrain neural crest generally is primed to respond to Bmp-4 and that in vitro, besides rhombomere 3 and 5, rhombomeres 2 and 6 are also sensitive to Bmp-4-sponsored death. As before, however, we find that rhombomere 4 will not respond to this factor. Our analysis of the Bmp-4 antagonists has uncovered a reason for this. Rhombomere 4 expresses elevated levels of the antagonist Noggin at its dorsal midline just as crest production from this segment commences and, as development proceeds, in the crest that migrates away from there. At these later stages, expression also becomes apparent in the migratory post-otic crest as it flows by the otic vesicle. An interesting feature of these domains of Noggin expression is that they lie between territories of Bmp-4 expression, suggesting that Noggin is acting to protect from Bmp-4-mediated cell death.
The presence of a muscularised pharynx with skeletal support is a fundamental vertebrate characteristic. Developmentally, the pharynx arises from the pharyngeal arches on either side of the head of vertebrate embryos. The development of the pharyngeal arches is complex involving a number of disparate embryonic populations, ectoderm, endoderm, neural crest and mesoderm, which must be co-ordinated to generate the components and overall identity of each of the arches. Previous studies suggested that it is the neural crest that plays a pivotal role in patterning the pharyngeal arches. It is now also becoming clear, however, that there are crest-independent patterning mechanisms. Therefore, pharyngeal arch patterning is more complex than was previously believed and there must be an integration of crest-dependent and -independent patterning mechanisms. BioEssays 23:54-61, 2001.
A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.
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Insulin and IGF-I binding has been studied in brown trout (Salmo trutta) wheat germ agglutinin semipurified receptors from embryos (organogenesis), larvae (yolk sac), juveniles (2.98 +/- 0.21 g bw) and adults (111.6 +/- 6.92 and 522 +/- 53 g bw). Embryos and larvae were sampled at 5 and 12 weeks after fertilization (December 1999 and February 2000) and juvenile and adults were taken simultaneously (July 1999) and under the same feeding conditions to minimize potential nutritional and seasonal effects. Insulin receptor number was maximal at 12 weeks (144 fmol/mg glycoprotein) and progressively decreased in subsequent samplings. No alterations in affinity were detected (K(d) range, 0.21-0.32 nM) and changes in number of receptor paralleled changes in total specific binding. IGF-I receptor number was highest at 5 weeks (1044 fmol/mg) and was significantly higher than values for insulin in all samplings. The affinity of IGF-I receptor did not change (K(d) range, 0.11-0.18 nM) but was consistently higher than that for the insulin receptor. A more rapid decrease of IGF-I binding and receptor number was found with age. However, the ratio of insulin/IGF-I binding established in 12-week-old larvae (0.18 +/- 0.01) was thereafter maintained at very similar values in juveniles and adults (0.15-0.17). Tyrosine kinase activity (TKA) for insulin receptors ranged between 136 and 183% and there were no significant changes with age. For the IGF-I receptor, TKA ranged from 174 to 281% and was significantly higher in 5-week-old larvae coincident with the highest levels of receptor number and declined gradually in parallel with binding levels. In conclusion, the greater abundance of IGF-I receptors during embryonic and larval development is maintained throughout juvenile and adult stages. This would suggest a key role for IGF-I in the growth and metabolism of trout muscle.
OBJECTIVE: Laparoscopically assisted vaginal hysterectomy (LAVH) has evolved into an alternative form of surgical management in the treatment of low-risk endometrial cancer. The purpose of this study was to determine whether low-risk endometrial cancer patients are subject to a higher incidence of positive peritoneal cytology when treated with LAVH compared to total abdominal hysterectomy (TAH). METHODS: We retrospectively reviewed the medical records of patients with low-risk endometrial cancer (grade 1--2 endometrioid type with no evidence of extrauterine spread or grade 3 with <50% myometrial invasion (MI), no cervical or adnexal involvement, and negative lymph nodes when sampled) treated at Memorial Sloan-Kettering Cancer Center from January 1993 to September 1999. We compared 131 patients treated with LAVH to 246 controls who underwent TAH. The two groups were compared for known prognostic factors including grade, MI, vascular space involvement, and lower uterine segment extension. RESULTS: The mean age of patients who underwent LAVH (61 years) was similar to that of the controls (62 years). Fourteen (10.3%) of the patients treated with LAVH had positive peritoneal cytology compared to only 7 (2.8%) of the control population. Factors including FIGO grade, myometrial invasion, and preoperative hysteroscopy did not influence the final results. When stratifying for these factors, the odds ratios of having positive peritoneal washings in those patients treated by LAVH were 5.2, 5.2, and 3.7, respectively. CONCLUSION: Treatment of low-risk endometrial cancer by LAVH is associated with a significantly higher incidence of positive peritoneal cytology. This may be due to the retrograde dissemination of cancer cells into the peritoneal cavity during uterine manipulation. The clinical significance of these findings is yet to be determined.