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Biomedical subjects

K Brown

Publications and source records attributed to K Brown.

At least 73 records · Page 4Linked to original sources
PubMed2001

Anticipation in familial chronic lymphocytic leukaemia.

Anticipation, a phenomenon in which an inherited disease is diagnosed at an earlier age in each successive generation of a family, has been demonstrated in certain heritable neurological disorders and in multiple myeloma, non-Hodgkin's lymphoma and other haematological neoplasms. The present study was conducted to determine whether anticipation occurs in familial chronic lymphocytic leukaemia (CLL). Fourteen published reports of multigenerational familial CLL were analysed for anticipation, together with 10 previously unreported families with familial CLL, and the difference in disease-free survival between generations was determined. The difference between age at onset for each affected parent-child pair was tested against the null hypothesis that there was no difference in age at onset. The age at onset of the studied cases was also compared with that of the Surveillance Epidemiology and End Results (SEER) Program of the U.S. National Cancer Institute. The median ages at onset in the child and parent generations of all families (51.0 and 72.0 years respectively) were significantly different (P < 0.000001), and the null hypothesis was rejected (P < 0.000001). A significant difference was observed between the ages of onset of the child generation and the SEER population (P < 0.00001), but not between the parent generation and the SEER population. Anticipation characterizes familial CLL.

Age of Onset↗
PubMed2001

A retrospective study of citalopram in adolescents with depression.

Recent evidence suggests that the selective serotonin reuptake inhibitors are safe and efficacious in treating juveniles with depression. However, citalopram has not been reported in adolescents with depression. This study assessed the effectiveness and tolerability of citalopram in all adolescents with depressive disorders treated naturalistically in a community mental health center during a 1-year interval. Medical charts were retrospectively reviewed for 21 adolescents treated with citalopram for major depression (n = 14), bipolar depression (n = 4), or dysthymia (n = 3). An independent rater compared last visit to baseline depression using the Clinical Global Impression (CGI) Severity and Improvement scales. Adolescents received citalopram for an average of 128.5 +/- 84 days at a final average dose of 26.5 +/- 13.1 mg/day. Sixteen of these 21 adolescents (76%) exhibited much to very much improvement as measured by the CGI, and severity of depression diminished significantly (z = 3.007, p < 0.0026). Mild side effects, including headaches, dizziness, nausea, sedation, agitation, and sweating were reported by 7 (33%) of the patients. These data suggest that citalopram may be effective, safe, and well tolerated in the treatment of adolescents with depressive disorders and that controlled trials are warranted in this population.

Adolescent↗
PubMed2001

Short-term dosing of alpha-hydroxytamoxifen results in DNA damage but does not lead to liver tumours in female Wistar/Han rats.

It is now generally accepted that activation of tamoxifen occurs as a result of metabolism to alpha-hydroxytamoxifen. In this study, alpha-hydroxytamoxifen was given to female Wistar/Han rats (0.103 or 0.0103 mmol/kg, intraperitoneally, daily for 5 days). This resulted in liver DNA damage, determined by (32)P-post-labelling, of 3333 +/- 795 or 343 +/- 68 adducts/10(8) nucleotides, respectively (mean +/- SD, n = 4). Following HPLC separation, the retention times of the major alpha-hydroxytamoxifen DNA adducts were similar to those seen following the administration of tamoxifen. However, after rats were treated with alpha-hydroxytamoxifen (0.103 mmol/kg) for 5 days and the animals kept for up to 13 months, no liver tumours developed (0/7 rats), even with phenobarbital promotion (0/5 rats). GST-P foci were detected in the liver, but only after 13 months was their number or area significantly increased over the corresponding controls. When alpha-hydroxytamoxifen was given to female lambda/lacI transgenic rats (0.103 mmol/kg orally for 10 days) and the animals killed 46 days later, there was an approximate 1.8-fold increase in mutation frequency but no significant increase in G:C to T:A transversions as described after tamoxifen treatment. It is concluded that DNA damage alone, resulting from the short-term administration of alpha-hydroxytamoxifen, is not sufficient to initiate liver tumours even with phenobarbital promotion. As with tamoxifen, long-term exposure may be required to allow promotion and progression of transformed cells.

Animals↗
PubMed2001

Role of short-term inhibition of factor Xa by FXV673 in arterial passivation: a study in a chronic model of thrombosis in conscious dogs.

Factor Xa (fXa) plays a pivotal role in the activation of the coagulation system during thrombosis, but, unlike GPIIb/IIIa receptor antagonists, the role of fXa inhibition in arterial passivation is not well defined. We compared the long-term antithrombotic efficacy of a direct fXa inhibitor, FXV673, and heparin after short-term infusion in conscious dogs. Dogs were instrumented surgically to induce carotid artery thrombosis by electrolytic injury. On day 1, dogs received a 3-h infusion of placebo (n = 10), FXV673 (100 microg/kg + 10 microg/kg/min, n = 7), or heparin (60 U/kg + 0.7 U/kg/min, n 7). Injury (100 microA) was initiated concomitantly for 1 h. The procedure was repeated on day 2 with injury of 200 microA for 3 h. Carotid artery blood flow (CBF) and coagulation parameters were monitored continuously for 3 h on days 1 and 2 and for 30 min on days 3, 4, and 5. On day 1 at 3 h, CBF in the placebo-treated group was 26% of baseline with 70% incidence of occlusion. None of the vessels occluded in the heparin and FXV673 groups; however, the CBF was significantly higher in the FXV673 group (92+/-8 ml/min versus 39+/-12 ml/min). Before injury on day 2, CBF recovered in all groups to 71-89% of baseline. After the second injury, all vessels in the placebo-treated group progressed to complete occlusion by 3 h. CBF was significantly higher in FXV673 group compared with heparin throughout the 3-h period. On days 3, 4, and 5 the placebo-treated vessels remained occluded, but the CBF in the heparin group was 33+/-20 ml/min, 55+/-11 ml/min and 68+/-12 ml/min, respectively, compared with 84+/-10 ml/min, 98+/-7 ml/min, and 99+/-10 ml/min in the FXV673 group. The arterial thrombus mass was significantly lower in FXV673 group (13+/-4 mg) compared with placebo (103+/-10 mg) and heparin (44+/-11 mg). In summary, these data demonstrate that short-term infusion of FXV673 was associated with long-term efficacy that was superior to standard heparin and underscore the role of direct fXa inhibition in arterial passivation.

Animals↗
PubMed2001

Recombinant chemosensory protein (CSP2) from the moth Mamestra brassicae: crystallization and preliminary crystallographic study.

Chemosensory proteins (CSPs) are small proteins (13 kDa on average) present in several sensory organs from a wide range of insect species. They are believed to be involved in chemoperception (olfaction or taste) and to play a role in chemical transport from air or water to chemosensitive receptors. Here, the first crystals of a CSP originating from the moth Mamestra brassicae (Mbra) proboscis and expressed as recombinant protein in Escherichia coli periplasm are reported. Crystals of MbraCSP2 were obtained by the hanging-drop vapour-diffusion method under the following conditions: 1 microl of a 46 mg ml(-1) protein solution in 50 mM Tris pH 8.0 containing cetyl alcohol as ligand (1:5 molar ratio) was mixed with 1 microl of well solution containing 30% PEG 4000, 0.2 M sodium acetate in 100 mM Tris at pH 8.4. The protein-cetyl alcohol complex crystallizes in space group P2(1), with unit-cell parameters a = 47.9, b = 49.7, c = 50.3 A, beta = 110.1 degrees. With two molecules in the asymmetric unit, the V(M) is 2.15 A(3) Da(-1) and the solvent content is 42%. A complete data set has been collected at 1.6 A resolution on beamline ID14-2 (ESRF, Grenoble). Se-Met expression has been performed with a view to solving the CSP2 structure with MAD data collection using the Se absorption edge.

Animals↗
PubMed2001

A cardiac prevention and rehabilitation programme for all patients at first presentation with coronary artery disease.

OBJECTIVE: To develop and test a cardiac prevention and rehabilitation programme for achieving sustained lifestyle, risk factor, and therapeutic targets in patients presenting for the first time with exertional angina, acute coronary syndromes, or coronary revascularisation. DESIGN: A descriptive study. SETTING: A hospital based 12 week outpatient programme. INTERVENTIONS: A multiprofessional family based programme of lifestyle and risk factor modification. MAIN OUTCOME MEASURES: Non-smoking status, body mass index, blood pressure, plasma cholesterol, use of prophylactic drugs. RESULTS: 158 patients (82% of 194 possible cases) were recruited over 15 months, with 72% completing the programme. Targets for achieving non-smoking status, blood pressure < 140/90 mm Hg, and total cholesterol < 4.8 mmol/l were achieved in 92%, 73%, and 62%, respectively, and the proportion on aspirin, beta blockers, and lipid lowering treatment was 95%, 58%, and 64% on referral back to general practice for continuing care. CONCLUSIONS: A comprehensive cardiac prevention and rehabilitation programme can be offered to all patients presenting for the first time with coronary heart disease, including those with exertional angina who are normally managed in primary care. Lifestyle, risk factor, and therapeutic targets can be successfully achieved in most patients with such a hospital based programme.

Adult↗
PubMed2000

Revisiting the catalytic CuZ cluster of nitrous oxide (N2O) reductase. Evidence of a bridging inorganic sulfur.

Nitrous-oxide reductases (N2OR) catalyze the two-electron reduction of N(2)O to N(2). The crystal structure of N2ORs from Pseudomonas nautica (Pn) and Paracoccus denitrificans (Pd) were solved at resolutions of 2.4 and 1.6 A, respectively. The Pn N2OR structure revealed that the catalytic CuZ center belongs to a new type of metal cluster in which four copper ions are liganded by seven histidine residues. A bridging oxygen moiety and two other hydroxide ligands were proposed to complete the ligation scheme (Brown, K., Tegoni, M., Prudencio, M., Pereira, A. S., Besson, S., Moura, J. J. G., Moura, I., and Cambillau, C. (2000) Nat. Struct. Biol. 7, 191-195). However, in the CuZ cluster, inorganic sulfur chemical determination and the high resolution structure of Pd N2OR identified a bridging inorganic sulfur instead of an oxygen. This result reconciles the novel CuZ cluster with the hitherto puzzling spectroscopic data.

Catalysis↗
PubMed2000

Multiparameter analysis of human epithelial tumor cell lines by laser scanning cytometry.

Laser scanning cytometry (LSC) is a relatively new slide-based technology developed for commercial use by CompuCyte (Cambridge, MA) for performing multiple fluorescence measurements on individual cells. Because techniques developed for performing four or more measurements on individual lymphoid cells based on light scatter as a triggering parameter for cell identification are not suitable for the identification of fixed epithelial tumor cells, an alternative approach is required for the analysis of such cells by LSC. Methods for sample preparation, event triggering, and the performance of multiple LSC measurements on disaggregated fixed human cells were developed using normal lymphocytes and two human breast cancer cell lines, JC-1939 and MCF-7, as test populations. Optimal conditions for individual cell identification by LSC were found to depend on several factors, including deposited cell density (cells per unit area), the dynamic range of probe fluorescence intensities, and intracellular distribution of the fluorescent probe. Sparsely deposited cells exhibited the least cell overlap and the brightest immunofluorescent staining. Major advantages of using DNA probes over a cytoplasmic immunofluorescent protein marker such as tubulin for event triggering are that the former exhibit greater fluorescence intensity within a relatively sharply demarcated nuclear region. The DNA-binding dye LDS-751 was found to be suboptimal for quantitative DNA measurements but useful as a triggering measurement that permits the performance of simultaneous fluorescein isothiocyanate-, phycoerythrin-, and indodicarbocyanine-based measurements on each cell. A major potential advantage of LSC over flow cytometry is the high yields of analyzable cells by LSC, permitting the performance of multiple panels of multicolor measurements on each tumor. In conclusion, we have developed and optimized a technique for performing multiple fluorescence measurements on fixed epithelial cells by LSC based on event triggering using the DNA-binding dye LDS 751. Although not ideal for quantitative measurements of cell DNA content, the large Stokes shift of this dye permits the performance of three or more additional fluorescence measurements on each cell.

Breast Neoplasms↗
PubMed2000

A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vaccine in young British infants.

A double-blind, randomised, controlled trial was conducted in 248 British infants to assess the immunogenicity and tolerability of three doses of a meningococcal group C/CRM (197) conjugate vaccine (Lederle Laboratories, USA) given at 2, 3 and 4 months. Control children received three doses of Hepatitis B vaccine (Engerix B(R); SmithKline Beecham). At 5 months of age, 100% of children receiving the conjugate vaccine had specific immunoglobulin G concentrations >2.0 microg/ml (n=116) compared with only 4% of control children (n=121). Those receiving the conjugate also had 2.5- and 1.6-fold higher geometric mean concentrations of PRP and diphtheria antibodies, respectively. The vaccine was well tolerated.

Antibodies, Bacterial↗
PubMed2000

Airway foreign bodies (FB): a 10-year review.

A retrospective chart review of children who had airway foreign body removed via direct laryngoscopy and bronchoscopy (DLB) from 1987-1997 was conducted in Children's Hospital, Boston. Patient characteristics noted included age, sex, and clinical presentation. Pre-operative radiographic findings, reason for delay in evaluation, DLB findings, length of procedure, reason for repeat DLB, and types of foreign body etc. were recorded. Serious complications from aspirated foreign bodies such as severe airway obstruction and death tend to occur in infants and younger children because of their small airway size. A history compatible with foreign body aspiration dictates diagnostic endoscopy with or without radiologic confirmation. Chest and airway radiographs supplemented by fluoroscopy can increase the ratio of correct and early diagnosis. Fluoroscopy should be universally accepted as an initial diagnostic technique in airway foreign body evaluation. Fluoroscopy is not a worthwhile investigation if a preceeding chest radiograph suggests the presence of a foreign body. Long-standing airway foreign bodies are associated with considerable morbidity, and early diagnosis remains the key to successful and uncomplicated management of foreign body aspiration. Education aimed at increasing diagnostic acumen of the physicians and heightening of public awareness are the most important steps needed to reduce the morbidity and mortality. Parents should be instructed to abstain from feeding nuts and seeds to young children and to keep small, potentially ingestible objects out of their reach.

Age Distribution↗
PubMed2000

Microbiology. Unlocking the secrets of the grim reaper.

On page 1594, researchers unveil the workings of YopJ, one of a group of nefarious proteins that Yersinia bacteria--including Y. pestis, the bacterium that is infamous for causing the bubonic plague--deploy. Early in the disease, Yersinia bacteria inject YopJ into macrophage cells of the immune system, where, the researchers have now found, YopJ acts like scissors, cleaving the macrophage proteins that would normally send an SOS to other immune cells for help. Leaving the macrophage stranded clears the way for other Yersinia proteins to destroy the cell.

Animals↗
PubMed2000

Viktor Hamburger. A lifelong fascination with the chick embryo.

Since the early days of developmental biology, Viktor Hamburger has inspired fellow scientists. Working with the simplest of tools--small glass needles, a basic microscope, a camera--he has asked, and helped to answer, some of biology's biggest questions. And at age 100, he isn't done yet.

Animals↗
PubMed2000

Ecology. Pacific salmon run hot and cold.

Using a novel technique, described on page 795, paleoceanographers have been able to chart the abundance of sockeye salmon in the Bristol Bay and Kodiak Island regions of Alaska over the past 300 years--by far the most complete record yet. Through time, they found, sockeye populations have alternately soared and slipped, following natural climate variations--well before commercial fishers began throwing nets over the sides of boats.

Alaska↗
PubMed2000

Biophysics. For certain shrimp, life's a snap.

On page 2114 of this issue, physicists report that a collapsing bubble outside the claw of the snapping shrimp Alpheus heterochaelis causes its characteristic clack. According to this new study, A. heterochaelis clamps its claw so rapidly that a water jet gushing from the claw first loses and then gains pressure, causing an air bubble in the jet to swell and collapse with a pronounced "snap!" The imploding bubble generates shock waves that stun nearby prey and ward off other shrimp, who have learned to keep their distance.

Air↗
PubMed2000

Ecology. Food fight drives evolution.

On page 441 of this issue, evolutionary biologists showcase the purple-throated carib hummingbird as a rare example of food supply--in this case, flower shape--spurring the evolution of a sexual dimorphism, or a feature that differs between males and females. On St. Lucia, an island in the West Indies, female caribs sport bills a third longer and twice as curved as those of their male counterparts--one of the most extreme bill differences between the sexes in any hummingbird species. In the paper, the researchers link these "whoppingly dimorphic bills" to the specific flowers the male and female caribs frequent.

Animals↗