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Biomedical subjects

J Robinson

Publications and source records attributed to J Robinson.

At least 181 records · Page 10Linked to original sources
PubMed1998

A versatile image analysis approach for simultaneous chromosome identification and localization of FISH probes.

Modern cytogenetic techniques, such as comparative genomic hybridization (CGH) and the multi-color fluorescence in situ hybridization (FISH) techniques of multiplex fluorescence in situ hybridization (M-FISH) and spectral karyotyping (SKY), require a coordinated banding analysis to maximize their usefulness. All of the methods currently used, including Giemsa (G-) banding, Alu banding, and 4',6-diamidino-2-phenyl-indole (DAPI) banding, have serious drawbacks. A simple and effective method to band chromosomes concurrently with FISH is needed. To address this problem, we stained chromosomes with DAPI and chromomycin A3, and then used an image analysis program to generate banding by dividing the image taken with a DAPI excitation filter by the image taken with a chromomycin A3 excitation filter. The result was a metaphase spread in which the chromosomes possessed a banding pattern characteristic of R-banding. The image analysis program was then used to generate linescans of pixel intensity versus relative position along the length of chromosomes that were banded using this technique, which we have called D/C R-banding. Each chromosome in a genome was represented by a characteristic scan profile, which was unaffected by FISH signals. Reference linescans were prepared by karyotyping D/C R-banded chromosomes for a given species, and then drawing lines along the length of the known chromosomes. The linescans were combined into a spreadsheet database, which was linked by dynamic data exchange to the image analysis program and normalized for length and intensity. The linescan of an unknown chromosome was then transferred to the spreadsheet, where it was normalized for length and intensity and overlaid on the linescans of each chromosome in the genome. Unknown chromosomes were identified by comparison of their graphs with graphs in the standardized reference genome. We have used this approach to create reference linescan karyotypes of several species, and to identify chromosomes on which FISH was performed.

Animals↗
PubMed1998

Macroangiopathy--does it play a role in young people?

Using a novel ultrasound method, brachial artery endothelial and smooth muscle physiology were studied in 20 adolescents with IDDM and in 20 nondiabetic subjects matched for age (13-22 years), gender and vessel size. Endothelium-dependent dilatation (EDD) was assessed in response to flow (EDD) and endothelium-independent vasodilatation after sublingual glyceryl trinitrate (GTN). Both EDD and GTN were reduced in those with IDDM compared with controls: 5 vs. 9%, (p = 0.0002) and 14 vs. 21% (p = 0.002). Abnormal EDD was found in 12 IDDM adolescents (diabetes duration 3.3-14.9 years). The mean urinary albumin excretion rate of the diabetic group with abnormal EDD was 5.76 +/- 2.82 vs. 8.05 +/- 4.88 microg/min in those with normal EDD (p = 0.25). In the diabetic adolescents there was no significant correlation observed between the test for early large vessel disease, HbAlc and tests for diabetic microangiopathy.

Adolescent↗
PubMed1998

The use of targets to improve the performance of health care providers: a discussion of government policy.

The aim of this discussion paper is to examine the advantages and drawbacks of employing targets, or performance indicators, to improve the performance of those delivering health care services. The paper is based on an examination of two target-setting policies initiated by Government: the 1992 Health of the Nation strategy and the 1990 General Practitioners' Contract. It is argued that the introduction of both the General Practitioners' Contract and the Health of the Nation have indeed been accompanied by improvements in performance, however, there are a number of problems with targets. They tend to focus on those things that are most easily measured, and they may foster complacency on the part of providers who have already achieved upper target limits, and defensiveness on the part of those performing badly. National targets may skew local priorities; they may also be unrealistic and unattainable for particular, less privileged population groups. They may serve to widen inequalities in health, and can exacerbate the 'inverse care law' by encouraging providers to direct their efforts at the more advantaged sections of society, where such efforts are more likely to pay off in terms of overall improvements in the target level achieved. Finally, the achievement of some targets will not necessarily result in better health outcomes. The paper concludes that a target-setting approach to improving the quality of care must be based on the use of appropriate indicators, and must take account of differences between more and less advantaged sections of society.

Contract Services↗
PubMed1998

Organ and tissue donation: are minorities willing to donate?

The Task Force on Organ Transplantation (DHHS,1986) addressed the issue of increasing organ donation. The Report of the Task Force recommended that "educational efforts aimed at increasing organ donation among minority populations be developed and implemented, so that the donor population will more closely reflect the ethnicity of potential transplant recipients, in order to gain the advantage of improved donor and recipient immunologic matching (DHHS,1986). Donor rates for minorities has increased as follows: 16% in 1988 to 23% in 1995 among cadaveric donors and 24% in 1988 to 28% in 1995 among living donors. The improvement in donor rates among minorities may positively affect the transplantation success rate experienced by organ recipients of the same race. Strategies must be implemented that will increase the effectiveness and frequency of communication between minority patients and the medical community. An increase in the effectiveness of communication between potential minority donor families and the health care community will contribute to the process of Consciousness Raising as discussed by Prochasksa. The result of increased awareness of the organ donation and transplantation process may have a favorable impact on organ donation. The media has, through public service announcements, paid advertising and entertainment programming, attempted to promote discussion of organ donation in the community and within families. Johnson et al. discussed Mexican-American and Anglo-American Attitudes Toward Organ Donation. The primary impediment contributing to the disparity of consent rates between Mexican-American and Anglo-American population occurs with regard to the donation of organs of relatives. Johnson stated that this impediment to organ donation can be effectively addressed by promoting family discussion. Communication within families will inform surviving next of kin of the desire of the deceased to be an organ donor and hence improve the likelihood of the donor family consenting to organ donation (Johnson et al., 1988). The promotion of communication within families must continue to be a goal of the transplant community regardless of race/ethnicity. Despite the efforts of the government, the transplant community, the media and the corporate sector to address the critical shortage of donors in the United States, the reality is that no community has the supply of donor organs suitable to meet the need.

Black or African American↗
PubMed1997

CD4-independent binding of SIV gp120 to rhesus CCR5.

CCR5 and CD4 are coreceptors for immunodeficiency virus entry into target cells. The gp120 envelope glycoprotein from human immunodeficiency virus strain HIV-1(YU2) bound human CCR5 (CCR5hu) or rhesus macaque CCR5 (CCR5rh) only in the presence of CD4. The gp120 from simian immunodeficiency virus strain SIVmac239 bound CCR5rh without CD4, but CCR5hu remained CD4-dependent. The CD4-independent binding of SIVmac239 gp120 depended on a single amino acid, Asp13, in the CCR5rh amino-terminus. Thus, CCR5-binding moieties on the immunodeficiency virus envelope glycoprotein can be generated by interaction with CD4 or by direct interaction with the CCR5 amino-terminus. These results may have implications for the evolution of receptor use among lentiviruses as well as utility in the development of effective intervention.

Amino Acid Sequence↗
PubMed1997

Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations of human anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins.

A panel of 14 human IgG monoclonal antibodies (MAbs) specific for envelope antigens of the human immunodeficiency virus type 1 (HIV-1), 2 high-titer human anti-HIV-1 immunoglobulin (HIVIG) preparations, and 15 combinations of MAbs or MAb/HIVIG were tested for their ability to neutralize infection of cultured human T cells (MT-2) with a chimeric simian immunodeficiency virus (SHIV-vpu+), which expressed HIV-1 IIIB envelope antigens. Eleven MAbs and both HIVIGs were neutralizing. When used alone, the anti-CD4-binding site MAb b12, the anti-gp41 MAb 2F5, and the anti-gp120 MAb 2G12 were the most potent. When combination regimens involving two MAbs targeting different epitopes were tested, synergy was seen in all paired MAbs, except for one combination that revealed additive effects. The lowest effective antibody concentration for 50% viral neutralization (EC50) and EC90 were achieved with combinations of MAbs b12, 2F5, 2G12, and the anti-V3 MAb 694/98D. Depending on the combination regimen, the concentration of MAbs required to reach 90% virus neutralization was reduced approximately 2- to 25-fold as compared to the dose requirement of individual MAbs to produce the same effect. Synergy of the combination regimens implies that combinations of antibodies may have a role in passive immunoprophylaxis against HIV-1. The ability of SHIV to replicate in rhesus macaques will allow us to test such approaches in vivo.

Animals↗
PubMed1997

Identification of a synthetic peptide that mimics an HIV glycoprotein 120 envelope conformational determinant exposed following ligation of glycoprotein 120 by CD4.

CD4 ligation of HIV envelope gp120 results in conformational changes in gp120 that lead to exposure of the gp41 fusogenic domain and fusion with the host cell membrane. One determinant at or near the CD4-binding site exposed on gp120 subsequent to CD4 binding is defined by two human MAbs termed 17b and 48d. These MAbs do not block CD4 binding to gp120; rather, their binding to gp120 is upregulated following CD4 binding. To determine if synthetic peptide mimetopes could be found that reflect conformational determinants on the surface of gp120, synthetic gp120 peptides from 10 divergent HIV isolates were screened for their ability to bind to 17b and 48d in ELISAs. Although MAb 48d binds to HIV IIIB recombinant gp120 protein, in our studies 48d selectively bound only to the HIV Can0A V3 peptide and not to HIV IIIB V3 peptide, whereas MAb 17b bound none of the peptides tested. Monoclonal antibody 48d bound to the HIV Can0A V3 peptide both in solid-phase ELISA and in solution in a competitive ELISA, but could not bind to HIV Can0A V3 peptide bound to human T cells. The HIV Can0A V3 peptide induced anti-HIV antibodies in rhesus monkeys that neutralized the laboratory-adapted HIV MN strain but did not induce antibodies that neutralized HIV IIIB/LAI, HIV SF-2, or HIV RF isolates, or that neutralized HIV primary isolates. These data suggested that the primary sequence of the HIV Can0A V3 loop exists in a conformer that mimicks a non-V3 determinant of native gp120 exposed subsequent to CD4 binding on the surface of gp120 of laboratory-adapted HIV strains. Structural studies of the Can0A V3 peptide and/or the 48d MAb may provide important information regarding the nature of gp120 conformational changes that occur following gp120 ligation by CD4.

Amino Acid Sequence↗
PubMed1997

Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection.

BACKGROUND: In infants and children with maternally acquired human immunodeficiency virus type 1 (HIV-1) infection, treatment with a single antiretroviral agent has limited efficacy. We evaluated the safety and efficacy of a three-drug regimen in a small group of maternally infected infants. METHODS: Zidovudine, didanosine, and nevirapine were administered in combination orally to eight infants 2 to 16 months of age. The efficacy of antiretroviral treatment was evaluated by serial measurements of plasma HIV-1 RNA, quantitative plasma cultures, and quantitative cultures of peripheral-blood mononuclear cells. RESULTS: The three-drug regimen was well tolerated, without clinically important adverse events. Within four weeks, there were reductions in plasma levels of HIV-1 RNA of at least 96 percent (1.5 log) in seven of the eight study patients. Over the 6-month study period, replication of HIV-1 was controlled in two infants who began therapy at 2 1/2 months of age. Plasma RNA levels were reduced by 0.5 to 1.5 log in five of the other six infants. CONCLUSIONS: Although further observations are needed, it appears that in infants with maternally acquired HIV-1 infection, combined treatment with zidovudine, didanosine, and nevirapine is well tolerated and has sustained efficacy against HIV-1.

Administration, Oral↗
PubMed1997

Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease.

L-Arginine is the physiological substrate for nitric oxide synthesis by the vascular endothelium. In hypercholesterolaemic rabbits, oral L-arginine reduces atheroma, improves endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion. The effect of oral L-arginine on endothelial physiology is unknown, however, in humans with established atherosclerosis. In a prospective, double-blind, randomised crossover trial, ten men aged 41 +/- 2 years with angiographically proven coronary atherosclerosis took L-arginine (7 g three times per day) or placebo for 3 days each, with a washout period of 10 days. After L-arginine, compared to placebo, plasma levels of arginine were increased (318 +/- 18 vs. 124 +/- 9 mumol/l, P < 0.01) and endothelium-dependent dilatation of the brachial artery (measured as the change in diameter in response to reactive hyperaemia, using external vascular ultrasound) was improved (4.7 +/- 1.1 vs. 1.8 +/- 0.7%, P < 0.04). No changes were seen in endothelium-independent dilatation of the brachial artery (measured as the change in diameter in response to sublingual nitroglycerine), blood pressure, heart rate or fasting lipid levels. Serum from six of the ten subjects after L-arginine and placebo was then added to confluent monolayers of human umbilical vein endothelial cells for 24 h, before human monocytes obtained by countercurrent centrifiguation elutriation were added and cell adhesion assessed by light microscopy. Adhesion was reduced following L-arginine compared to placebo (42 +/- 2 vs. 50 +/- 1%, P < 0.01). In young men with coronary artery disease, oral L-arginine improves endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion.

Administration, Oral↗
PubMed1997

Characterization of adult alpha- and beta-globin genes in the zebrafish.

Developmental switching of hemoglobins (Hbs) occurs in most vertebrates, yet the cellular and molecular basis for this process remains elusive. The zebrafish is a new genetic and developmental system that can be used to study embryogenesis, and mutants with a variety of defects in hematopoiesis have recently been derived. To initiate our studies on Hb switching in this organism, we have characterized the globins expressed in the adult. Reversed-phase high performance liquid chromatography and mass spectrometric analyses of adult peripheral blood hemolysates showed that there are three major alpha globins and two beta globins in circulating erythroid cells. In addition, we have isolated and characterized zebrafish adult alpha- and beta-globin cDNA clones that encode some of these globins. High levels of alpha- and beta-globin gene expression were detected in adult erythroid cells, whereas embryonic erythroid cells expressed little, if any, of these RNAs. We have also shown that the alpha- and beta-globin genes are tightly linked on the same chromosome and are arrayed in a 3'-5' to 5'-3' configuration, respectively. The characterization of these genes and regulatory elements in this globin locus will provide insight into the process of globin gene transcription. With these reagents, future studies of Hb switching in zebrafish mutants with defective hematopoiesis will be possible.

Amino Acid Sequence↗
PubMed1997

Intramuscular ceftriaxone compared with oral amoxicillin-clavulanate for treatment of acute otitis media in children.

UNLABELLED: Two hundred and fifteen children aged 4 months 6 years with acute otitis media (AOM) were randomized to be treated either by a single i.m. injection of ceftriaxone, 50 mg/kg, with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM (109 patients) or amoxicillin clavulanate 12.5 mg tid (106 patients). The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate, 4.6% and 4.7%, respectively (standard error for intergroup difference -2.87%, 95% confidence interval -5.62% to 5.87%). No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology, otoscopy findings, relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30, 60 and 90. Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone--25 out of 84 (29.4%) versus 11 out of 81 (13.6%) (P = 0.012). CONCLUSION: Ceftriaxone injection(s) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children. Although not recommended as routine, ceftriaxone can be considered in the management of acute otitis media under special circumstances, particularly in cases when the ability to tolerate or absorb oral drugs is compromised, in children refusing or unable to take oral therapy or when the compliance is questionable.

Acute Disease↗
PubMed1997

Probabilistic secretion of quanta and the synaptosecretosome hypothesis: evoked release at active zones of varicosities, boutons, and endplates.

A quantum of transmitter may be released upon the arrival of a nerve impulse if the influx of calcium ions through a nearby voltage-dependent calcium channel is sufficient to activate the vesicle-associated calcium sensor protein that triggers exocytosis. A synaptic vesicle, together with its calcium sensor protein, is often found complexed with the calcium channel in active zones to form what will be called a "synaptosecretosome." In the present work, a stochastic analysis is given of the conditions under which a quantum is released from the synaptosecretosome by a nerve impulse. The theoretical treatment considers the rise of calcium at the synaptosecretosome after the stochastic opening of a calcium channel at some time during the impulse, followed by the stochastic binding of calcium to the vesicle-associated protein and the probability of this leading to exocytosis. This allows determination of the probabilities that an impulse will release 0, 1, 2,... quanta from an active zone, whether this is in a varicosity, a bouton, or a motor endplate. A number of experimental observations of the release of transmitter at the active zones of sympathetic varicosities and boutons as well as somatic motor endplates are described by this analysis. These include the likelihood of the secretion of only one quantum at an active zone of endplates and of more than one quantum at an active zone of a sympathetic varicosity. The fourth-power relationship between the probability of transmitter release at the active zones of sympathetic varicosities and motor endplates and the external calcium concentration is also explained by this approach. So, too, is the fact that the time course of the increased rate of quantal secretion from a somatic active zone after an impulse is invariant with changes in the amount of calcium that enters through its calcium channel, whether due to changes consequent on the actions of autoreceptor agents such as adenosine or to facilitation. The increased probability of quantal release that occurs during F1 facilitation at the active zones of motor endplates and sympathetic boutons is predicted by the residual binding of calcium to a high-affinity site on the vesicle-associated protein. The concept of the stochastic operation of a synaptosecretosome can accommodate most phenomena involving the release of transmitter quanta at these synapses.

Action Potentials↗
PubMed1997

Psychosocial adjustment to unsuccessful IVF and GIFT treatment.

Twenty-one couples for whom in vitro fertilisation (IVF) or GIFT treatment failed were followed-up 15-30 months after treatment and compared with 20 couples for whom IVF had been successful. Current mental health status, quality of life and marital adjustment were assessed via standardised questionnaires. In addition, couples' experiences of IVF/GIFT treatment were explored via a semi-structured interview. Questionnaire results showed that unsuccessful IVF/GIFT recipients cannot be distinguished from general population norms. However, these couples reported more emotional distress relative to those whom treatment had worked and females in particular indicated a lower quality of life. Couples who had at least one child prior to IVF/GIFT treatment tended to show greater emotional distress at follow-up. Both groups gave similar accounts of the positive and negative aspects of IVF/GIFT treatment, but the unsuccessful group felt less supported by the IVF Unit staff and were less satisfied with the counseling they received. The data indicate that post-treatment counseling may be particularly important for facilitating positive reconstructions of the IVF experience when treatment is unsuccessful.

Adaptation, Psychological↗
PubMed1997

Efficiency of the polymerase chain reaction amplification of the uid gene for detection of Escherichia coli in contaminated water.

Direct detection of Escherichia coli from polluted river water was achieved using polymerase chain reaction (PCR) amplification of the uid gene. Amplification using DNA from environmental samples resulted in non-specific DNA fragments. Specific amplification was achieved through use of the touch-down PCR procedure. Targeting the uidA structural region of the gene gave reproducibly better amplification than targeting the uidR regulatory region. The data demonstrate conditions for optimal specific detection.

Bacteriological Techniques↗
PubMed1997

Remote monitoring. Expanding a successful system.

A successful telemetry placement system moves into five medical/surgical areas and two step-down units. The updated equipment included an alarm gateway with an arrhythmia detection system. Telemetry signals are transmitted to a pager worn by nurses; remote display monitors allow nurses to eyeball arrhythmias and reset their alarm without going to a central station.

Equipment Failure↗
PubMed1997

An anatomic study of the internal mammary veins: clinical implications for free-tissue-transfer breast reconstruction.

The anatomy of the internal mammary vessels is poorly understood and thought to be unreliable clinically for use as a recipient vein in free-tissue-transfer breast reconstruction. This study of 10 fresh cadaver thoracic cavities demonstrated by anatomic and dye resection studies that the internal mammary veins become smaller (< or = 2 mm) distally (fourth rib) and bifurcate [left (90 percent) > right (40 percent)], becoming unsuitable for consistent venous anastomoses at or below the fourth interspace. Furthermore, this study suggests that the most consistent interval is the third rib, which offers an appropriate recipient vein (40 percent > or = 3 mm on the left and 70 percent > or = 3 mm on the right). However, at the fourth interspace, 20 percent of the cadaver specimens had a vein on one side that was 1 mm or less and therefore unsuitable as a recipient. This enhanced understanding of the anatomy (size, location, and consistency) of the internal mammary recipient veins offers our patients another recipient option to enhance the safety and technical ease of microvascular breast reconstruction.

Algorithms↗
PubMed1997

Spirometry and airway reactivity in elite track and field athletes.

OBJECTIVES: To characterize spirometry and to document the incidence of exercise-induced bronchospasm (EIB) during competition in elite track and field athletes. DESIGN: Spirometry was performed in 120 men and 69 women athletes before competition and peak expiratory flows in 50 men and 23 women athletes before and after competition. SETTING: The 1991 (Randalls Island, NY, U.S.A.) and the 1993 (Eugene, OR, U.S.A.) National Track and Field Championships (World Championship team-qualifying meet). PARTICIPANTS: American track and field athletes who met World Championship qualifying standards. MEASUREMENTS: Spirometry (Cybermedic, Inc., Boulder, CO, U.S.A.) and peak expiratory flows (Personal Best, Healthscan Products, Cedar Grove, NJ, U.S.A.)--the best of three reproducible efforts. RESULTS: Male sprinters had lower vital capacities than other track athletes, whereas both male and female field (throwing) athletes had larger vital capacities than both runners and other field athletes. Decreases of 10% peak expiratory flows were found in 10% of men and 26% of women track athletes within 15 min after competition. The incidence was higher in longer-distance events. Most participants did not have a history of asthma. CONCLUSIONS: A higher-than-expected prevalence of EIB was found in high-level track athletes. The results suggest that spirometry and/or peak flows should be measured in track athletes because small decreases in airflow may impair training or performance, a condition that is easily treated.

Adult↗