Search PubMed⌕ Search

Biomedical subjects

B Watson

Publications and source records attributed to B Watson.

At least 19 recordsLinked to original sources

A QTL located on chromosome 4A associated with dormancy in white- and red-grained wheats of diverse origin.

Improved resistance to preharvest sprouting in modern bread wheat (Triticum aestivum. L.) can be achieved via the introgression of grain dormancy and would reduce both the incidence and severity of damage due to unfavourable weather at harvest. The dormancy phenotype is strongly influenced by environmental factors making selection difficult and time consuming and this trait an obvious candidate for marker assisted selection. A highly significant Quantitative Trait Locus (QTL) associated with grain dormancy and located on chromosome 4A was identified in three bread wheat genotypes, two white- and one red-grained, of diverse origin. Flanking SSR markers on either side of the putative dormancy gene were identified and validated in an additional population involving one of the dormant genotypes. Genotypes containing the 4A QTL varied in dormancy phenotype from dormant to intermediate dormant. Based on a comparison between dormant red- and white-grained genotypes, together with a white-grained mutant derived from the red-grained genotype, it is concluded that the 4A QTL is a critical component of dormancy; associated with at least an intermediate dormancy on its own and a dormant phenotype when combined with the R gene in the red-grained genotype and as yet unidentified gene(s) in the white-grained genotypes. These additional genes appeared to be different in AUS1408 and SW95-50213.

Australia↗

Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine.

All subjects in this clinical study gave informed written consent, and guidelines of the authors' institution regarding human experimentation were observed in the conduct of the study. A booster dose of vaccine given to 18 adolescents (immunized as children) and 7 older adults immunized 13 years earlier with a 3-dose course of recombinant hepatitis B vaccine induced a strong secondary antibody response, demonstrating that the vaccinees retained immunologic memory for HbsAG. Within one week, booster vaccination induced an 11 to 24-fold rise in the GMT of anti-HBs which continued, reaching 52 to 319-fold after 4 weeks. Significantly even the 5 individuals with less than 10 mIU/ml of anti-HBs prior to the booster all had impressive responses to the booster dose.

Adolescent↗

The use of left heart bypass in adult and recurrent coarctation repair.

OBJECTIVES: Paraplegia following coarctation repair occurs in 0.4% of infants. However, for older children, adults and re-operations, the incidence can be as high as 2.6%. Yet there is no consensus on the need for spinal cord protection or the optimal method. This paper reports our experience with left heart bypass (LHB) in adult and re-do coarctation. METHODS: Between 1997 and 2000, nine patients underwent elective resection of coarctation (three re-dos, two balloons) with a mean age of 17.9 years (range, 8-44) and weight of 52 kg (range, 17.3-109). The mean trans-coarctation gradient was 29.6 mmHg (range, 20-45). Patients were placed on LHB using a centrifugal pump with full heparinization through a fourth-space thoracotomy. Patients were cooled to 31-34 degrees C for additional spinal cord protection. Repair was carried out with an inter-positional graft (5/9), a Gore-Tex patch (2/9) or end-to-end anastomosis (2/9). The mean cross-clamp and bypass times were 36.4 (range, 19-65) and 40.3 min (range, 22-70), respectively. RESULTS: No patient developed transient or permanent paraplegia. The mean peak creatinine was 80 micromol/l (range, 51-123). CONCLUSIONS: LHB is simple, easy and safe to implement, and is the only technique capable of maintaining independent upper and lower body perfusion pressure. Potentially, it provides the best spinal cord protection, and extends the margin of safety and time to execute an accurate repair.

Adolescent↗

Mitochondrial DNA mutations in black Americans with hypertension-associated end-stage renal disease.

For the majority of hypertensive cases, no gene or combination of genes and environmental factors clearly leading to hypertension has been identified. Studies to identify "hypertension" genes have focused on the assessment of markers and candidate genes in the nuclear genome. In this study, we have chosen to assess the mitochondrial genome as a site of mutations possibly contributing to susceptibility to hypertension in black Americans who have progressed to end-stage renal disease (H-ESRD). The mitochondrial genomes of 58 H-ESRD and 58 normotensive individuals were systematically analyzed by means of a high-resolution restriction analysis. After stratification by the presence or absence of an African continent-specific HpaI site gain at bp 3,592, differences in the frequencies of mitochondrial DNA (mtDNA) restriction variants in both groups were examined by chi-square analyses. A total of six variants was identified with significant differences in one or both cohorts. An A10398G DdeI mutation in the ND3 gene was significantly increased in the H-ESRD cohort (H-ESRD, P = 0.048; normotensives, P = 0.20), as was an HaeIII T6620C/G6260A double mutation in the CO1 gene (H-ESRD, P = 0.05; normotensives, P = 0.48). The remaining four variants were a G2758A mutation in the 16SrRNA gene (identified by RsaI), T10810C in the ND4 gene (identified by HinfI), a G7028A/T7055C double mutation in the CO1 gene (identified by AluI), and finally, a A10086G mutation in the ND3 gene (identified by TaqI; also causing an Asn-->Asp amino acid change). The RsaI and HinfI variants were in strong linkage disequilibrium with the HpaI site and not amenable to further analysis. After correction of all P values for multiple comparisons, the ND3 A10086G (Asn-->Asp) mutation shown by TaqI remained statistically significant (P = 0.0036) in the H-ESRD cohort, not in the normotensive cohort. To the best of our knowledge, this is the first report of an increased prevalence of mitochondrial gene variants in hypertensive individuals. In addition, we have identified single-nucleotide polymorphisms in flanking regions of these genes. Although replication and further assessment are necessary, the current results support our hypothesis that mtDNA may account for a portion of hypertensive cases in black Americans with ESRD.

Black or African American↗

A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory.

OBJECTIVES: Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant HB vaccine, Recombivax HB (2 or 3 doses of 5 or 10 microg given over 4 or 6 months), induce protective anti-hepatitis B surface antibody [anti-HBsAb] levels (>/=10 mIU/mL) comparable to the recommended regimen (5 microg at 0 and 1, and 6 months); 2) measured early antibody response after a single dose; and 3) assessed immunologic memory after 2- and 3-dose regimens. DESIGN: One thousand twenty-six adolescents were randomized to 1 of 5 treatment groups (10 microg at 0 and 4 or 0 and 6 months; 5 microg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open trial. Anti-HBsAb was measured in all participants just before and 1 month after the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb response to a booster dose 2 years later was examined to assess immunologic memory in participants vaccinated with 5 microg at 0 and 6 or 0, 1, and 6 months. RESULTS: All regimens induced >/=10 mIU/mL of anti-HBs in >/=95% of vaccinees. Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regimens using the following: 1) 10 versus 5 microg; 2) 3 versus 2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccinees given one 10-microg dose had >/=10 mIU/mL of anti-HBsAb versus 41.6% after one 5-microg dose. Participants vaccinated with either two or three 5-microg doses retained robust immunologic memory. CONCLUSIONS: . The results of this study show that a 2-dose regimen of Recombivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-microg doses may be of significant benefit for vaccinees who are poorly compliant or deviate from the intended vaccination schedule.

Adolescent↗

Antibody responses of healthy infants to concurrent administration of a bivalent haemophilus influenzae type b-hepatitis B vaccine with diphtheria-tetanus-pertussis, polio and measles-mumps-rubella vaccines.

OBJECTIVE: To confirm that children given a bivalent Haemophilus influenzae type b-hepatitis B vaccine (bivalent Hib-HB vaccine; COMVAX) concurrently with priming doses of diphtheria-tetanus-pertussis vaccine (DTP), a booster dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP), inactivated or oral polio vaccine (IPV or OPV) and measles-mumps-rubella vaccine (M-M-R(II)) have satisfactory antibody responses to all antigens. DESIGN: 126 healthy 2-month-old infants were scheduled to receive bivalent Hib-HB vaccine concurrently with DTP (2 and 4 months of age), OPV or IPV (random allocation to OPV or IPV at 2 months of age; OPV at 4 and 14 to 15 months of age), DTaP and M-M-R(II) (14 to 15 months of age). A response was judged "adequate" if the lower bound of the 95% confidence interval on the proportion of vaccinees having a critical antibody level was <10 percentage points below prediction. RESULTS: Antibodies to hepatitis B virus surface antigen, H. influenzae polysaccharide, diphtheria toxin, tetanus toxin, pertussis agglutinogens, pertussis toxin (as measured by enzyme immunoassay but not by Chinese hamster ovary cell assay), pertussis filamentous haemagglutinin after a booster dose of DTaP, poliovirus type 2, measles virus, and mumps virus all equalled or exceeded expected levels. Antibodies to rubella virus and pertussis filamentous haemagglutinin (after priming doses of DTP) fell slightly, and in the case of rubella significantly, below predicted levels. Antibodies to poliovirus types 1 and 3 were also below expectation after 2 doses of polio vaccine but were adequate following a third dose of vaccine. CONCLUSION: Concurrent administration of bivalent Hib-HB vaccine with priming doses of DTP, a booster dose of DTaP, OPV, IPV, or M-M-R(II) was well tolerated and, with the possible exception of rubella, did not substantially impair the antibody response to any antigen.

Antibodies, Bacterial↗

Expression and regulation of normal and polymorphic epithelial sodium channel by human lymphocytes.

Gene expression, protein expression, and function of amiloride-sensitive sodium channels were examined in human lymphocytes from normal individuals and individuals with Liddle's disease. Using reverse transcriptase polymerase chain reactions, expression of all three cloned epithelial sodium channel (ENaC) subunits was detected in lymphocytes. Polyclonal antibodies to bovine alpha-ENaC bound to the plasma membrane of normal and Liddle's lymphocytes. A quantitative analysis of fluorescence-tagged ENaC antibodies indicated a 2.5-fold greater surface binding of the antibodies to Liddle's lymphocytes compared with normal lymphocytes. The relative binding intensity increased significantly (25%; p < 0.001) for both normal and Liddle's cells after treatment with 40 microM 8-CPT-cAMP. Amiloride-sensitive whole cell currents were recorded under basal and cAMP-treated conditions for both cell types. Liddle's cells had a 4.5-fold larger inward sodium conductance compared with normal cells. A specific 25% increase in the inward sodium current was observed in normal cells in response to cAMP treatment. Outside-out patches from both cell types under both treatment conditions revealed no obvious differences in the single channel conductance. The P(open) was 4.2 +/- 3.9% for patches from non-Liddle's cells, and 27.7 +/- 5.4% in patches from Liddle's lymphocytes. Biochemical purification of a protein complex, using the same antibodies used for the immunohistochemistry, yielded a functional sodium channel complex that was inhibited by amiloride when reconstituted into lipid vesicles and incorporated into planar lipid bilayers. These four independent methodologies yielded findings consistent with the hypotheses that human lymphocytes express functional, regulatable ENaC and that the mutation responsible for Liddle's disease induces excessive channel expression.

Amiloride↗

Association of a haplotype for tumor necrosis factor in siblings with late-onset Alzheimer disease: the NIMH Alzheimer Disease Genetics Initiative.

Tumor necrosis factor (TNF), a proinflammatory cytokine, may be involved in the pathogenesis of Alzheimer disease (AD) based on observations that senile plaques have been found to upregulate proinflammatory cytokines. Additionally, nonsteroidal anti-inflammatory drugs have been found to delay and prevent the onset of AD. A collaborative genome-wide scan for AD genes in 266 late-onset families implicated a 20 centimorgan region at chromosome 6p21.3 that includes the TNF gene. Three TNF polymorphisms, a -308 TNF promoter polymorphism, whose TNF2 allele is associated with autoimmune inflammatory diseases and strong transcriptional activity, the -238 TNF promoter polymorphism, and the microsatellite TNFa, whose 2 allele is associated with a high TNF secretion, were typed in 145 families consisting of 562 affected and unaffected siblings. These polymorphisms formed a haplotype, 2-1-2, respectively, that was significantly associated with AD (P = 0.005) using the sibling disequilibrium test. Singly, the TNFa2 allele was also significantly associated (P = 0.04) with AD in these 145 families. This TNF association with AD lends further support for an inflammatory process in the pathogenesis of AD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:823-830, 2000.

Age of Onset↗

Skeletal muscle recovery after tenotomy and 7-day delayed muscle length restoration.

Rabbit extensor digitorum longus (EDL) tendons were cut with the muscle active (active tenotomy, AT) or with the EDL at rest (passive tenotomy, PT). One, 7, and 21 days after tenotomy, contractile testing was performed. A second experiment was performed in which EDL tendons underwent PT and, after a 7-day delay, muscle-tendon units were restored to their original length. Maximum isometric tension dropped precipitously 1 day after either AT or PT to approximately 50% of normal and continued to decline by day 7. In contrast to PT, where peak tension (P(0)) decreased further by 21 days, after AT, P(0) partially recovered. Differences in muscle mass, cross-sectional area, fiber type, and sarcomere number did not explain the differential response. One day after length restoration of muscles, P(0) rapidly increased by approximately 40%. These observations have implications for understanding the outcome of muscle-tendon unit injury and surgical repair.

Animals↗

Postexposure effectiveness of varicella vaccine.

OBJECTIVE: 1) To describe the postexposure effectiveness of varicella vaccine in a homeless shelter; and 2) to demonstrate an effective public health intervention and its implications. DESIGN: A prospective observational study. SETTING: A women and children's shelter in Philadelphia with 2 cases of varicella before intervention. OUTCOME MEASURES: Varicella in vaccinated and unvaccinated shelter residents; vaccine effectiveness for prevention of varicella when administered after exposure among children <13 years of age. RESULTS: Sixty-seven shelter residents received varicella vaccine after exposure, including 42 children <13 years of age. One child who was unvaccinated developed varicella, but no vaccinated child developed typical disease. Vaccine effectiveness was 95.2% (95% CI, 81.6%-98.8%) for prevention of any disease and 100% for prevention of moderate or severe disease among the children <13 years of age. CONCLUSION: When used within 36 hours after exposure to varicella in a setting where close contact occurred, varicella vaccine was highly effective in preventing further disease. This study provides support for the recent recommendation by the Advisory Committee on Immunization Practices to administer varicella vaccine after exposure: this practice should minimize the number of moderate or severe cases of disease and prevent prolonged outbreaks.

Chickenpox↗

The use of school-based vaccination clinics to control varicella outbreaks in two schools.

School-based vaccination clinics were offered in 2 schools experiencing varicella outbreaks. The clinics raised coverage of susceptible children from 52.9% to 92.2% and from 68.8% to 85.3% in the 2 schools, respectively. Although routine immunization and school-entry requirements are the best strategies for preventing outbreaks, school-based vaccination clinics may greatly increase coverage and shorten outbreaks.

Adolescent↗

Heterogeneity of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi, and European origin populations: cross sectional study.

OBJECTIVE: To compare coronary risk factors and disease prevalence among Indians, Pakistanis, and Bangladeshis, and in all South Asians (these three groups together) with Europeans. DESIGN: Cross sectional survey. SETTING: Newcastle upon Tyne. PARTICIPANTS: 259 Indian, 305 Pakistani, 120 Bangladeshi, and 825 European men and women aged 25-74 years. MAIN OUTCOME MEASURES: Social and economic circumstances, lifestyle, self reported symptoms and diseases, blood pressure, electrocardiogram, and anthropometric, haematological, and biochemical measurements. RESULTS: There were differences in social and economic circumstances, lifestyles, anthropometric measures and disease both between Indians, Pakistanis, and Bangladeshis and between all South Asians and Europeans. Bangladeshis and Pakistanis were the poorest groups. For most risk factors, the Bangladeshis (particularly men) fared the worst: smoking was most common (57%) in that group, and Bangladeshis had the highest concentrations of triglycerides (2.04 mmol/l) and fasting blood glucose (6.6 mmol/l) and the lowest concentration of high density lipoprotein cholesterol (0.97 mmol/l). Blood pressure, however, was lowest in Bangladeshis. Bangladeshis were the shortest (men 164 cm tall v 170 cm for Indians and 174 cm for Europeans). A higher proportion of Pakistani and Bangladeshi men had diabetes (22.4% and 26.6% respectively) than Indians (15.2%). Comparisons of all South Asians with Europeans hid some important differences, but South Asians were still disadvantaged in a wide range of risk factors. Findings in women were similar. CONCLUSION: Risk of coronary heart disease is not uniform among South Asians, and there are important differences between Indians, Pakistanis, and Bangladeshis for many coronary risk factors. The belief that, except for insulin resistance, South Asians have lower levels of coronary risk factors than Europeans is incorrect, and may have arisen from combining ethnic subgroups and examining a narrow range of factors.

Adult↗

Varicella vaccine: progress 4 years after licensure.

The concerns raised by parents and physicians about varicella immunization are reasonable and need to be acknowledged. We believe, however, that the available information strongly suggests that these concerns should not impede implementation of universal immunization against varicella. In fact, some of these concerns are best resolved by universal immunization. Some people argue that only a small percentage of people with varicella will have a significant complication and therefore vaccinating all is unnecessary. Yet, a small percentage of 3.5 to 4 million cases per year is not an insignificant number. There is a precedent for changing immunization practice because of relatively small risks when the risks in question are serious. For example, immunization practice has changed because we have decided that 8 to 10 cases per year of vaccine-associated paralytic poliomyelitis (of 770 million doses) is unacceptable. Vaccination has been the most important health care advance of the past 40 years. Now that varicella can be added to the list of vaccine-preventable diseases, we can help our patients avoid both the common and the uncommon but much more severe complications of this disease, as well as the considerable economic burden. Although the chances that any individual will have a complication are small, if your patient is the statistic, the odds are meaningless. How can we continue to accept even mild disease from varicella, let alone severe complications, when the disease is now preventable by an effective, safe vaccine? Not immunizing patients puts them at medical risk and us at legal risk.

Chickenpox Vaccine↗

Management of palpable breast lumps. Consensus guideline for family physicians.

OBJECTIVE: To describe an approach to managing women who present with palpable breast lumps. QUALITY OF EVIDENCE: Databases were searched from 1990 to 1998 using the search terms breast lumps, breast diseases, and breast cysts. Bibliographies of the articles obtained were searched for further relevant titles. Most evidence on management of breast cysts was obtained from cohort studies. Evidence on family physicians' approach to managing breast lumps is based on a review of the 1998 Canadian consensus guidelines and a review of a 1998 consensus guideline by 12 University of Toronto surgical oncologists (U of T guidelines). MAIN MESSAGE: Family physicians can manage women presenting with breast lumps if they have skill in breast cyst aspiration. Most breast cysts can be cured in minutes, thus avoiding unwarranted anxiety and eliminating unnecessary additional investigations and referrals. Women presenting with solid lesions should be referred to a surgeon. CONCLUSIONS: Breast cyst aspiration is a simple technique family physicians can use to either cure breast lumps or define appropriate cases for referral.

Algorithms↗

Alpha-2 macroglobulin is genetically associated with Alzheimer disease.

Alpha-2-macroglobulin (alpha-2M; encoded by the gene A2M) is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits. Analysis of a deletion in the A2M gene at the 5' splice site of 'exon II' of the bait region (exon 18) revealed that inheritance of the deletion (A2M-2) confers increased risk for AD (Mantel-Haenzel odds ratio=3.56, P=0.001). The sibship disequilibrium test (SDT) also revealed a significant association between A2M and AD (P=0.00009). These values were comparable to those obtained for the APOE-epsilon4 allele in the same sample, but in contrast to APOE-epsilon4, A2M-2 did not affect age of onset. The observed association of A2M with AD did not appear to account for the previously published linkage of AD to chromosome 12, which we were unable to confirm in this sample. A2M, LRP1 (encoding the alpha-2M receptor) and the genes for two other LRP ligands, APOE and APP (encoding the amyloid beta-protein precursor), have now all been genetically linked to AD, suggesting that these proteins may participate in a common neuropathogenic pathway leading to AD.

Age of Onset↗

Hepatitis B immunization of Asian Pacific Islanders in the United States.

BACKGROUND: There are numerous strategies recommended in the United States for control of the hepatitis B virus, including universal vaccination of infants and adolescents and vaccination of all high risk populations. A recent hepatitis B vaccination program conducted in Philadelphia, PA, focused on effective ways to educate and vaccinate the high risk Asian Pacific Islander population. METHODS: Multiple intervention activities were used for both health care providers and Asian Pacific Islander community members, including one-to-one educational programs. RESULTS: Intervention activities did increase hepatitis B vaccination coverage to 34%, but coverage increase was less than has been shown with other programs. CONCLUSION: The intervention program, however, may have a long-lasting positive impact on vaccination coverage because postintervention, study participant health care providers began to offer a more flexible vaccination delivery system. It is likely that the total cost of $135943 for all intervention activities will prevent future costly cases of chronic hepatitis B and its serious related sequelae among this high risk population.

Adolescent↗