Biomedical subjects
B Green
Publications and source records attributed to B Green.
Binding of correolide to K(v)1 family potassium channels. Mapping the domains of high affinity interaction.
Correolide, a novel nortriterpene natural product, potently inhibits the voltage-gated potassium channel, K(v)1.3, and [(3)H]dihydrocorreolide (diTC) binds with high affinity (K(d) approximately 10 nM) to membranes from Chinese hamster ovary cells that express K(v)1.3 (Felix, J. P., Bugianesi, R. M., Schmalhofer, W. A., Borris, R., Goetz, M. A., Hensens, O. D., Bao, J.-M., Kayser, F. , Parsons, W. H., Rupprecht, K., Garcia, M. L., Kaczorowski, G. J., and Slaughter, R. S. (1999) Biochemistry 38, 4922-4930). Mutagenesis studies were used to localize the diTC binding site and to design a high affinity receptor in the diTC-insensitive channel, K(v)3.2. Transferring the pore from K(v)1.3 to K(v)3.2 produces a chimera that binds peptidyl inhibitors of K(v)1.3 with high affinity, but not diTC. Transfer of the S(5) region of K(v)1.3 to K(v)3.2 reconstitutes diTC binding at 4-fold lower affinity as compared with K(v)1.3, whereas transfer of the entire S(5)-S(6) domain results in a normal K(v)1.3 phenotype. Substitutions in S(5)-S(6) of K(v)1.3 with nonconserved residues from K(v)3.2 has identified two positions in S(5) and one in S(6) that cause significant alterations in diTC binding. High affinity diTC binding can be conferred to K(v)3.2 after substitution of these three residues with the corresponding amino acids found in K(v)1.3. These results suggest that lack of sensitivity of K(v)3.2 to diTC is a consequence of the presence of Phe(382) and Ile(387) in S(5), and Met(458) in S(6). Inspection of K(v)1.1-1.6 channels indicates that they all possess identical S(5) and S(6) domains. As expected, diTC binds with high affinity (K(d) values 7-21 nM) to each of these homotetrameric channels. However, the kinetics of binding are fastest with K(v)1.3 and K(v)1.4, suggesting that conformations associated with C-type inactivation will facilitate entry and exit of diTC at its binding site. Taken together, these findings identify K(v)1 channel regions necessary for high affinity diTC binding, as well as, reveal a channel conformation that markedly influences the rate of binding of this ligand.
The optimal radiologic method for assessing spinal canal compromise and cord compression in patients with cervical spinal cord injury. Part II: Results of a multicenter study.
STUDY DESIGN: A multicenter, retrospective study using computed tomographic and magnetic resonance imaging data to establish quantitative, reliable criteria of canal compromise and cord compression in patients with cervical spinal cord injury. OBJECTIVES: To develop and validate a radiologic assessment tool of spinal canal compromise and cord compression in cervical spinal cord injury for use in clinical trials. SUMMARY OF BACKGROUND DATA: There are few quantitative, reliable criteria for radiologic measurement of cervical spinal canal compromise or cord compression after acute spinal cord injury. METHODS: The study included 71 patients (55 men, 16 women; mean age, 39.7 +/- 18.7 years) with acute cervical spinal cord injury. Causes of spinal cord injury included motor vehicle accidents (n = 36), falls (n = 20), water-related injuries (n = 8), sports (n = 5), assault (n = 1), and farm accidents (n = 1). Canal compromise was measured on computed tomographic scan and T1- and T2-weighted magnetic resonance imaging, and cord compression at the level of maximum injury was measured on T1- and T2-weighted magnetic resonance imaging. All films were assessed by two independent observers. RESULTS: There was a strong correlation of canal compromise and/or cord compression measurements between axial and midsagittal computed tomography, and between axial and midsagittal T2-weighted magnetic resonance imaging. Spinal canal compromise assessed by computed tomography showed a significant although moderate correlation with spinal cord compression assessed by T1- and T2-weighted magnetic resonance imaging. Virtually all patients with canal compromise of 25% or more on computed tomographic scan had evidence of some degree of cord compression on magnetic resonance imaging, but a large number of patients with less than 25% canal compromise on computed tomographic scan also had evidence on magnetic resonance imaging of cord compression. CONCLUSIONS: In patients with cervical spinal cord injury, the midsagittal T1- and T2-weighted magnetic resonance imaging provides an objective, quantifiable, and reliable assessment of spinal cord compression that cannot be adequately assessed by computed tomography alone.
Surgical treatment for acute spinal cord injury study pilot study #2: evaluation of protocol for decompressive surgery within 8 hours of injury.
Acute spinal cord injury (SCI) is a major public health problem for which there is still only limited treatment available. The National Acute Spinal Cord Injury Study-2 (NASCIS-2) and -3 clinical trials demonstrated that the use of acute pharmacotherapy with methylprednisolone can attenuate the secondary injury cascade if administered within 8 hours of acute SCI. However, no trial has been performed to examine whether acute surgical decompressive procedures within this critical 8-hour time window can improve patients' neurological outcome. The purpose of the current prospective Surgical Treatment for Acute Spinal Cord Injury Study (STASCIS) pilot study was to determine the feasibility of obtaining a radiological diagnosis of spinal canal compromise of 25% or more and to perform spinal cord (C3-T1) decompressive procedures by 8 hours postinjury. One of the following three decompressive methods was used: 1) traction alone; 2) traction and surgery; or 3) surgery alone. Twenty-six patients from eight North American centers were entered into the study between 1996 and 1997. Significant difficulties were encountered in many centers in performing immediate magnetic resonance imaging examination in patients with acute SCI. Fewer than 10% of acute cervical SCI patients could be enrolled into this protocol mainly because the combination of the required time for rescue, resuscitation, transport, imaging study, and surgical preparation exceeded the 8-hour injury-to-decompressive surgery window. Eleven patients underwent decompressive procedures initially by being placed in traction at a mean time of 10.9 hours postinjury. Those patients not undergoing this procedure underwent decompressive surgery at a mean time of 40.1 hours. However, the surgical decompressive procedure was completed within 12 hours in seven patients. As a result of these findings, several major changes have been made to the STASCIS protocol for early decompressive therapy.
The biosciences in the pre-registration nursing curriculum: staff and students' perceptions of difficulties and relevance.
This paper considers the problematic position of the biological sciences in pre-registration nurse education--'The Bioscience Question'. There is no consensus and little research on the appropriate content and depth of bioscience knowledge required by nurses. Attempts to apportion curriculum time for the biosciences are confounded by the difficulty experienced by nursing students with this area. Within one university department, a survey was undertaken to investigate the perceptions of pre-registration students, and their teachers, of the teaching and learning of biological science, in comparison with other areas of the curriculum. Our findings concur with others that the biosciences are a source of disproportionate difficulty and anxiety to nursing students. Among the students, but not the lecturers, there was some, by no means universal, support for the suggestion that these problems could be reduced by a reallocation of curriculum time in favour of the biosciences. Although it was agreed that bioscience theory should be related more closely to nursing practice, there was no evidence that this lessened the students' difficulties with the subject. In contrast to lecturers, students felt the biosciences to be one of the areas of the pre-registration curriculum most relevant to clinical practice.
Occupation and risk of hip fracture.
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Low frequency of CYP2A6 gene polymorphism as revealed by a one-step polymerase chain reaction method.
Human cytochrome P450 2A6 (CYP2A6) has been shown to metabolically activate carcinogens and mutagens. Genetic polymorphisms for CYP2A6 have been reported previously in different ethnic groups using a two-step polymerase chain reaction (PCR) method to identify CYP2A6*1, CYP2A6*2 and CYP2A6*3. Moreover, a new truncated allele has been recently identified in a Japanese population. We report here a one-step PCR amplification of the CYP2A6 gene from human genomic DNA and the detection of intact CYP2A6 alleles by restriction enzyme digestion. The diagnostic exon (exon 3) of the CYP2A6 gene was amplified from human genomic DNA with a primer pair. The forward primer is unique to the CYP2A6 gene, which eliminates previous problems in amplifying two highly homologous CYP2A genes, CYP2A7 and CYP2A13, in humans. The resulting PCR products (214 bp) were digested with XcmI or DdeI to detect the presence of CYP2A6*2 or CYP2A6*3 alleles, respectively. The allelic frequencies for CYP2A6*2 were 2.3% (n = 320) in the Caucasian and 0.7% (n = 71) in the Chinese populations, respectively. CYP2A6*3 allelic frequency in the Chinese population was 0.7%; while no CYP2A6*3 allele was detected in the Caucasian population. The allelic frequencies are relatively low and the reason for this discrepancy between different methods is discussed.
Focus on olanzapine.
Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine) is a novel antipsychotic agent of the theinobenzodiazepine class developed by Eli Lilly & Co. It has a pleotrophic pharmacology and affects the dopaminergic, serotonergic, muscarinic and adrenergic systems. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to additional serotonergic effects. Clinical studies and trials suggest that olanzapine is comparable or superior to haloperidol and may be superior to risperidone in terms of efficacy and side-effect profiles. The starting dose of olanzapine is a single dose of 10 mg. The drug reaches peak plasma levels in 5-8 h, and has a half-life of about 35 h, depending on metabolism. The recommended maximum dose is 20 mg daily, but higher doses have been employed. Abnormalities of the QTc interval on ECG are unlikely to occur and so there is no need for a baseline ECG as with sertindole, which has recently been withdrawn. The most common side-effects are somnolence and weight gain. About 40% of patients in clinical trials gain weight--especially if they are on a high starting dose and if they were underweight pre-treatment. Reported evidence to date suggests that olanzapine is relatively less likely to produce sexual dysfunction. In general, weight gain and sexual dysfunction are of great concern to people taking antipsychotics and the side-effect profile of any antipsychotic may affect compliance. Olanzapine's general efficacy and side-effect profile suggest that, unforeseen post-marketing complications notwithstanding, olanzapine deserves a major place in the first-line management of psychotic disorders.
Focus on quetiapine.
Quetiapine fumarate is a novel dibenzothiazepine antipsychotic developed by Zeneca. It is marketed under the trade name 'Seroquel'. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. The initial hope of investigators was that quetiapine would have antipsychotic potential and that it might share some of the properties of clozapine without its toxicity to white blood cells. The effective dosage range is usually 300-450 mg/day split into two doses. The dose is titrated upwards from 25 mg twice daily from day 1 to 300 mg/day on day 4. Elderly patients or patients with liver problems should be started on lower doses. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 mg/day to 750 mg/day, and is an effective treatment for negative symptoms. Somnolence is the most common adverse event. Abnormalities of the QT interval on ECG appear very infrequently and there is no need for a baseline ECG or blood pressure monitoring, as used to be the case with sertindole. There is no need for haematological monitoring as with clozapine. Quetiapine, across the full dosage range, is associated with no greater extrapyramidal symptoms than placebo. Quetiapine's general efficacy and side-effect profile suggest that, unless there are unforeseen post-marketing complications, it deserves a major place in the initial and long-term management of schizophreniform disorders.
Long-term followup of the North American multicenter UroLume trial for the treatment of external detrusor-sphincter dyssynergia.
PURPOSE: We determine the long-term efficacy and safety of the UroLume stent as minimally invasive treatment for external detrusor-sphincter dyssynergia in spinal cord injured men. MATERIALS AND METHODS: A total of 160 spinal cord injured men with a mean age plus or minus standard deviation of 36.3 +/- 12.1 years (range 16 to 74) were prospectively treated with an endoprosthesis at 15 centers as part of the North American UroLume trial for external detrusor-sphincter dyssynergia. Urodynamic parameters, including voiding pressure, residual urine volume and bladder capacity, were compared before treatment and at 1, 2, 3, 4 and 5 years after treatment. RESULTS: Mean voiding pressure was 75.1 +/- 28.2 cm. water before treatment in the 160 patients, and 37.4 +/- 23.9 at year 1 in 97, 39.5 +/- 22.2 at year 2 in 84, 42.6 +/- 27.3 at year 3 in 61, 46.3 +/- 33.2 at year 4 in 57 and 44.2 +/- 28.9 cm. at year 5 in 41 after stent insertion (p <0.001). Residual urine volume decreased after stent placement and was maintained throughout the 5-year followup (p <0.001). Mean cystometric capacity remained constant from 269 +/- 155 before insertion to 337 +/- 182 ml. 5 years later (p = 0.17). Hydronephrosis and autonomic dysreflexia improved or stabilized in most patients with functioning stents. Stent explant was necessary in 24 patients (15%), of whom 4 (16.7%) had another stent implanted. CONCLUSIONS: The UroLume stent demonstrates long-term safety and efficacy for the treatment of external detrusor-sphincter dyssynergia. The outcome was similar in men with and without previous sphincterotomy.
Mortality rates after cataract extraction.
Senile cataract may be a marker of generalized tissue aging. We examined this hypothesis using population-based linked health data. We hypothesized that any such association would diminish with increased use of cataract surgery. Mortality rates of those 50-95 years of age undergoing cataract surgery in British Columbia during either 1985 or 1989 were compared with the provincial population of comparable age who did not undergo cataract surgery during the study period. The 1985 cohort included 8,262 patients undergoing surgery and a comparison population of 804,303, and the 1989 cohort included 11,952 patients and a comparison population of 839,393. Using Cox regression, for the 1985 cohort, the hazard ratios for dying during follow-up were 3.2 for males 50-54.9 years of age [95% confidence limits (CL) = 2.0, 5.0] and 3.3 for females (95% CL = 1.9, 5.7). Hazard ratios for older age groups decreased with age. We also fit an additive risk model that produced excess mortalities that were less age dependent. In the 1985 analysis, these ranged from +7.1 per 1,000 (95% CL = +0.44, +13.76) to +20.3 (95% CL = +13.24, +27.36) for males and -17.5 (95% CL = -28.28, -6.72) to +2.0 (95% CL = -2.12, +6.12) for females. Findings for the 1989 analyses were similar, indicating that the association between cataracts and generalized aging remained constant despite a large increase in the use of cataract surgery.
Giant toads Bufo marinus in Australia and Venezuela have antibodies against 'ranaviruses'.
A serological survey was conducted for antibodies against 'ranaviruses' in the giant toad Bufo marinus in Australia and Venezuela. Sera containing antibodies against 'ranaviruses' were found in both countries. In Australia positive antibodies were identified in populations throughout most of the known range of B. marinus. Results were confirmed by immunofluorescence and immunoelectron microscopy where a characteristic staining pattern of 'ranaviruses' in infected cells was observed. Whilst a 'ranavirus(es)' has been isolated from populations of B. marinus in Venezuela, no virus has been isolated from Australian B. marinus populations. The significance of 'ranavirus' sero-positive B. marinus in Australia is discussed.
Modulation of the biological functions of galectin-3 by matrix metalloproteinases.
Galectin-3 is an important intracellular and extracellular lectin which is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The exact physiological role of the protein is presently not known. We have previously demonstrated that recombinant human galectin-3 is a novel substrate for metalloproteinases, particularly MMP-2 and MMP-9. These enzymes are capable of efficiently cleaving the Ala62-Tyr63 bond of the ca. 30 kDa galectin-3, generating a 22 kDa fragment with intact carbohydrate recognition domain and a ca. 9 kDa polypeptide comprising the amino terminal end of the intact galectin-3. In this study, we analyzed interactions of the 22 kDa fragment of galectin-3 with immobilized laminins. We have also compared the hemagglutination as well as homodimerization potentials of this fragment with that of intact galectin-3. Our data suggest that cleavage of galectin-3 by metalloproteinases; (a) alters the carbohydrate recognition domain of the lectin so that it binds more tightly to the glycoconjugates and, (b) reduces selfassociation of the galectin molecules thereby abrogating the biological properties dependent on such associations or homodimerization.
Social role functioning by adolescents with psychiatric disorders.
OBJECTIVE: To identify aspects of social role functioning that are impaired in adolescents with specific psychiatric disorders in order to improve the psychiatric taxonomy and clinical knowledge base. METHOD: Adolescents in four urban public schools were screened for mental health problems. Structured psychiatric interviews (National Institute of Mental Health Diagnostic Interview Schedule for Children Version 2.2) with 288 adolescents and their mothers were used to identify youths with psychiatric disorders, and 10 aspects of social role functioning were assessed. Aspects of social role functioning that discriminated between youths with and without psychiatric disorders and between those with emotional disorders and those with disruptive disorders were identified for boys and for girls. RESULTS: Boys with any type of disorder and all youths with disruptive disorders had significant, consistent impairment in academic performance and several other areas of functioning. Youths with emotional disorders, especially girls, demonstrated impairment in social activity participation and peer acceptance, but girls with disorders were not as consistently different from those without as were the boys with emotional disorders. CONCLUSIONS: Role functioning differs in important ways between youths with and without psychiatric disorders and between girls and boys with disorders. The results underscore the importance of investigating observable aspects of role behavior in order to improve the timely detection and effective management of psychiatric disorders in youth.
Reliability and validity of the adolescent health profile-types.
OBJECTIVES: The purpose of this study was to demonstrate the preliminary reliability and validity of a set 13 profiles of adolescent health that describe distinct patterns of health and health service requirements on four domains of health. METHODS: Reliability and validity were tested in four ethnically diverse population samples of urban and rural youths aged 11 to 17-years-old in public schools (N = 4,066). The reliability of the classification procedure and construct validity were examined in terms of the predicted and actual distributions of age, gender, race, socioeconomic status, and family type. School achievement, medical conditions, and the proportion of youths with a psychiatric disorder also were examined as tests of construct validity. RESULTS: The classification method was shown to produce consistent results across the four populations in terms of proportions of youths assigned with specific sociodemographic characteristics. Variations in health described by specific profiles showed expected relations to sociodemographic characteristics, family structure, school achievement, medical disorders, and psychiatric disorders. CONCLUSIONS: This taxonomy of health profile-types appears to effectively describe a set of patterns that characterize adolescent health. The profile-types provide a unique and practical method for identifying subgroups having distinct needs for health services, with potential utility for health policy and planning. Such integrative reporting methods are critical for more effective utilization of health status instruments in health resource planning and policy development.
Characterization of unmyelinated axons uniting epidermal and dermal immune cells in primate and murine skin.
The present study was undertaken to characterize further the structure and function of cutaneous nerves which we have previously shown to associate with skin immune cells (Hosoi et al., Nature 1993: 363:159). Ultrastructurally, axons were prominent within the superficial dermis and epidermis in neonatal murine skin, but they were inconspicuous in adult murine and primate skin. Immunohistochemical and immunoultrastuctural evaluation of normal adult human and simian skin for neural cell adhesion molecule (N-CAM), however, defined a plexus of axons surrounding superficial dermal mast cells and extending as delicate, vertical branches into the overlying epidermal layer. Antibodies to neuropeptides substance P, calcitonin gene-related peptide, and to nerve cell-specific clathrin (LCb subunit) also reacted with this neural plexus. Double labeling disclosed intimate associations of N-CAM-positive axons with dermal chymase-positive mast cells as well as with epidermal CD1a-positive Langerhans' cells by confocal scanning laser microscopy. Functionally, capsaicin applied to forearm skin revealed by 6 h discharge of mast cell chymase and induction of E-selectin in adjacent microvascular endothelium, events consistent with release of substance P from axons and subsequent stimulation of cytokine-mediated mast cell-endothelial interaction. Identical application of capsaicin to human skin xenografted to immunodeficient mice, and thus experimentally lacking in unmyelinated axons, failed to show similar findings. These results provide additional support to the concept that an elaborate network of cutaneous axons may play a functional role in regulation of skin inflammation and immunity.
The bldB gene encodes a small protein required for morphogenesis, antibiotic production, and catabolite control in Streptomyces coelicolor.
Mutants blocked at the earliest stage of morphological development in Streptomyces species are called bld mutants. These mutants are pleiotropically defective in the initiation of development, the ability to produce antibiotics, the ability to regulate carbon utilization, and the ability to send and/or respond to extracellular signals. Here we report the identification and partial characterization of a 99-amino-acid open reading frame (ORF99) that is capable of restoring morphogenesis, antibiotic production, and catabolite control to all of the bldB mutants. Of the existing bld mutants, bldB is of special interest because the phenotype of this mutant is the most pleiotropic. DNA sequence analysis of ORF99 from each of the existing bldB mutants identified base changes either within the coding region of the predicted protein or in the regulatory region of the gene. Primer extension analysis identified an apparent transcription start site. A promoter fusion to the xylE reporter gene showed that expression of bldB is apparently temporally regulated and that the bldB gene product is involved in the regulation of its own expression.
Haemoglobin Le Lamentin (alpha 20 (B1) His-->Gln) in a British family: identification by electrospray mass spectrometry.
The first identification of haemoglobin Le Lamentin (alpha 20 (B1) His-->Gln) in a British patient is described. The patient was a 69 year old asymptomatic white male being screened for diabetes, whose blood was undergoing its first ever analysis for glycated haemoglobin using a Glycomat II analyser. Identification of the haemoglobin variant was by electrospray mass spectrometry.