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Biomedical subjects

J M White

Publications and source records attributed to J M White.

At least 91 records · Page 5Linked to original sources
PubMed1999

Collection of peripheral blood progenitor cells (PBPC) based on a rising WBC and platelet count significantly increases the number of CD34+ cells.

The kinetics of mobilization and optimal timing of peripheral blood progenitor cell (PBPC) collection were evaluated in 190 patients with multiple myeloma undergoing stem cell harvest after mobilization with cyclophosphamide, prednisone and G-CSF. There was a strong correlation between the WBC count and the number of CD34+ cells circulating in peripheral blood (r = 0.875). Initiating leukapheresis based on rising WBC and platelet counts rather than on a fixed day increased the mean number of CD34+ cells 115% (9.7 to 20.9 x 10(6) CD34+ cells/kg; P = 0.010) for the total of all leukaphereses and 59% for the total of all CD34-selected products (5.1 to 8.1 x 10(6) CD34+ cells/kg; P = 0.011). Although the yield and purity of the CD34-selected product were not significantly affected (P > or = 0.071), the percentage of patients with concentrations of CD34+ cells in the initial leukapheresis of > 1% increased from 47% to 70% (P = 0.004). The mean purity of the selected product was related to the starting percentage: 48.9% if < 1% and 81.5% if > or = 1% (P < 0.001). Collection of stem cells based on rising WBC and platelet counts significantly increased the number of CD34+ cells in leukaphereses and CD34-selected products in comparison with collection on a fixed day.

Adult↗
PubMed1999

Possible hazards of cryogen use with pulsed dye laser. A case report and summary.

BACKGROUND: Pulsed dye laser treatment of port-wine stains is safe and effective. However, the pain associated with this treatment is often difficult to tolerate, especially for children. A laser-coupled delivery system known as dynamic epidermal cooling has recently been developed to improve local anesthesia. OBJECTIVE: To report laser ignition of a commercially-available, hand-held cryogen spray used for local anesthesia, and describe possible mechanisms of the fire; to define the chemical characteristics of other skin coolants suitable and unsuitable for skin cooling with laser treatment. METHODS: Case report and literature review. CONCLUSIONS: Clinicians must be aware of the thermodynamic properties, potential for skin damage, cost and environmental consequences of commercially available cryogens before considering their use for topical anesthesia with laser surgery.

Anesthesia, Local↗
PubMed1999

Optimization strategies for production of mammalian embryos by nuclear transfer.

In order to optimize each of the individual steps in the nuclear transfer procedure, we report alternative protocols useful for producing recipient cytoplasts and for improving the success rate of nuclear transfer embryos in cattle, rhesus monkey, and hamster. Vital labeling of maternal chromatin/spindle is accomplished by long wavelength fluorochromes Sybr14 and rhodamine labeled tubulin allowing constant monitoring and verification during enucleation. The use of Chinese hamster ovary (CHO) donor cells expressing the viral influenza hemagglutinin fusion protein (HA-300a+), to adhere and induce fusion between the donor cells and enucleated cow, rhesus and hamster oocytes was examined. Cell surface hemagglutinin was activated with trypsin prior to nuclear transfer and fusion was induced by a short incubation of a newly created nuclear transfer couplet at pH 5.2 at room temperature. Donor cell cytoplasm was dynamically labeled with CMFDA, or further transfected with the green fluorescence protein (GFP) gene, so that fusion could be directly monitored using live imaging. High rates of fusion were observed between CHO donor cells and hamster (100%), rhesus (100%), and cow recipient cytoplasts (81.6%). Live imaging during fusion revealed rapid intermixing of cytoplasmic components between a recipient and a donor cell. Prelabeled donor cytoplasmic components were uniformly distributed throughout the recipient cytoplast, within minutes of fusion, while the newly introduced nucleus remained at the periphery. The fusion process did not induce activation as evidenced by unchanged distribution and density of cortical granules in the recipient cytoplasts. After artificial activation, the nuclear transfer embryos created in this manner were capable of completing several embryonic cell divisions. These procedures hold promise for enhancing the efficiency of nuclear transfer in mammals of importance for biomedical research, agriculture, biotechnology, and preserving unique, rare, and endangered species.

Animals↗
PubMed1999

A specific point mutant at position 1 of the influenza hemagglutinin fusion peptide displays a hemifusion phenotype.

We showed previously that substitution of the first residue of the influenza hemagglutinin (HA) fusion peptide Gly1 with Glu abolishes fusion activity. In the present study we asked whether this striking phenotype was due to the charge or side-chain volume of the substituted Glu. To do this we generated and characterized six mutants with substitutions at position 1: Gly1 to Ala, Ser, Val, Glu, Gln, or Lys. We found the following. All mutants were expressed at the cell surface, could be cleaved from the precursor (HA0) to the fusion permissive form (HA1-S-S-HA2), bound antibodies against the major antigenic site, bound red blood cells, and changed conformation at low pH. Only Gly, Ala, and Ser supported lipid mixing during fusion with red blood cells. Only Gly and Ala supported content mixing. Ser HA, therefore, displayed a hemifusion phenotype. The hemifusion phenotype of Ser HA was confirmed by electrophysiological studies. Our findings indicate that the first residue of the HA fusion peptide must be small (e.g., Gly, Ala, or Ser) to promote lipid mixing and must be small and apolar (e.g., Gly or Ala) to support both lipid and content mixing. The finding that Val HA displays no fusion activity underscores the idea that hydrophobicity is not the sole factor dictating fusion peptide function. The surprising finding that Ser HA displays hemifusion suggests that the HA ectodomain functions not only in the first stage of fusion, lipid mixing, but also, either directly or indirectly, in the second stage of fusion, content mixing.

3T3 Cells↗
PubMed1999

Effect of accommodative adaptation on static and dynamic accommodation in emmetropia and late-onset myopia.

PURPOSE: Prolonged near work is considered to be an environmental factor leading to the development of late-onset myopia. Accommodation may be the specific mechanism underlying the association between near work and late-onset myopia. To determine whether late-onset myopes have abnormal accommodation, we compared accommodative static responses and dynamic facilities before and after a near task in two groups of subjects, emmetropes and late-onset myopes. METHODS: In experiment 1, the accommodative stimulus/response function with monocular viewing and the dark focus (the accommodative response in the dark) were objectively measured with a Canon R-1 infrared optometer before (preadaptation) and after (postadaptation) a 20-min near task. In experiment 2, monocular accommodative facility (AF) and dark focus were measured before and after the near task. Facility was measured as the subjective time needed to clear an accommodative target (20/40 letters) at 40 cm through +/-2.00 D lenses. The time between when the subject flipped the lenses from viewing through the +2.00 D to the -2.00 D lenses was recorded by a computer. RESULTS: In both experiments, inward shifts of the dark focus were observed after the near task. In experiment 1, after the near task, static accommodative responses also showed a small but statistically significant inward shift. Neither postadaptation effect differed between refractive groups. The only difference between groups was that late-onset myopes had a lower slope of the accommodative stimulus/response function, both pre- and postadaptation. In experiment 2, both refractive groups showed the same results. After the near task, the duration for accommodation from near to far (relaxation) increased but the duration for accommodation from far to near (stimulation) did not change. CONCLUSIONS: Late-onset myopes have shallower accommodative stimulus/response functions. As suggested in a previous study, this may be due to their reduced sensitivity to defocus. In both emmetropes and late-onset myopes, the near task causes an increase in static accommodative responses. Although our results show it to be a small increase, it is consistent with predictions of Hung and Semmlow's model of accommodation. In both emmetropes and late-onset myopes, the near task also increases the duration for relaxing accommodation, but not for stimulating accommodation. This suggests there are two subsystems which may adapt to prolonged accommodation differently.

Accommodation, Ocular↗
PubMed1999

Nonlinear alteration of transient vergence dynamics after sustained convergence.

BACKGROUND: Adaptation models of the horizontal disparity vergence system assume a nonadaptable transient component. They also predict identical postadaptation dynamics during convergence and divergence movements. METHOD: To test the adaptation property of the transient component, a set of experiments were performed in which closed-loop vergence dynamics measured before and after sustained convergence were compared, primarily by comparing the peak vergence velocity, occurrence time of peak vergence velocity, and steady-state vergence posture. Vergence dynamics after durations of 30, 60, and 90 s of sustained convergence were compared with those after a control duration of 5 s. RESULTS: The peak divergence velocity was reduced by about 25% within 30 s of sustained vergence. However, the peak convergence velocity was unchanged for all the exposure durations. Additionally, for all durations, the peak divergence velocity was significantly higher than peak convergence velocity. In contrast to peak velocities, the occurrence time of peak convergence and divergence velocity did not differ significantly and remained unchanged for all durations. CONCLUSIONS: The transient component is adaptable. Furthermore, the adaptation is direction dependent and affects divergence and convergence dynamics differently, thereby suggesting involvement of separate pathways for convergence and divergence in the vergence sensorimotor control.

Accommodation, Ocular↗
PubMed1999

Effects of relaxing music on cardiac autonomic balance and anxiety after acute myocardial infarction.

BACKGROUND: Acute myocardial infarction places additional demands on an already compromised myocardium. Relaxing music can induce a relaxation response, thereby reversing the deleterious effects of the stress response. OBJECTIVES: To compare the effects of relaxing music; quiet, uninterrupted rest; and "treatment as usual" on anxiety levels and physiological indicators of cardiac autonomic function. METHODS: A 3-group repeated measures experimental design was used. Forty-five patients, 15 per group, with acute myocardial infarction were assigned randomly to 20 minutes of (1) music in a quiet, restful environment (experimental group); (2) quiet, restful environment without music (attention); or (3) treatment as usual (control). Anxiety levels and physiological indicators were measured. RESULTS: Immediately after the intervention, reductions in heart rate, respiratory rate, and myocardial oxygen demand were significantly greater in the experimental group than in the control group. The reductions in heart rate and respiratory rate remained significantly greater 1 hour later. Changes in heart rate, respiratory rate, and myocardial oxygen demand in the attention group did not differ significantly from changes in the other 2 groups. The 3 groups did not differ with respect to systolic blood pressure. Increases in high-frequency heart rate variability were significantly greater in the experimental and attention groups than in the control group immediately after the intervention. State anxiety was reduced in the experimental group only; the reduction was significant immediately and 1 hour after the intervention. CONCLUSIONS: Patients recovering from acute myocardial infarction may benefit from music therapy in a quiet, restful environment.

Analysis of Variance↗
PubMed1999

Mechanisms of fatal opioid overdose.

There has been increasing recognition of the problem of fatal opioid overdose. This review examines the pharmacological basis of respiratory depression following opioid administration. Respiration is controlled principally through medullary respiratory centres with peripheral input from chemoreceptors and other sources. Opioids produce inhibition at the chemoreceptors via mu opioid receptors and in the medulla via mu and delta receptors. While there are a number of neurotransmitters mediating the control of respiration, glutamate and GABA are the major excitatory and inhibitory neurotransmitters, respectively. This explains the potential for interaction of opioids with benzodiazepines and alcohol: both benzodiazepines and alcohol facilitate the inhibitory effect of GABA at the GABAA receptor, while alcohol also decreases the excitatory effect of glutamate at NMDA receptors. Heroin and methadone are the major opioids implicated in fatal overdose. Heroin has three metabolites with opioid activity. Variation in the formation of these metabolites due to genetic factors and the use of other drugs could explain differential sensitivity to overdose. Metabolites of methadone contribute little to its action. However, variation in rate of metabolism due to genetic factors and other drugs used can modify methadone concentration and hence overdose risk. The degree of tolerance also determines risk. Tolerance to respiratory depression is less than complete, and may be slower than tolerance to euphoric and other effects. One consequence of this may be a relatively high risk of overdose among experienced opioid users. While agonist administration modifies receptor function, changes (usually in the opposite direction) also result from use of antagonists. The potential for supersensitivity to opioids following a period of administration of antagonists such as naltrexone warrants further investigation. While our understanding of the pharmacological basis of opioid-related respiratory depression has advanced, better understanding of the role of heroin metabolites, the metabolism of methadone, drug interactions and tolerance would all be of considerable value in knowing how best to respond to this problem.

Drug Interactions↗
PubMed1998

Solving the complementarity dilemma: evolving strategies for simultaneous hermaphroditism.

We introduce a complementarity dilemma, a two-player, binary response game in which the playoffs are highest when the two players respond differently. Using the classifier EvA, we determine the evolutionary dynamics and structure of strategies that evolve to play an iterated version of this game, and we relate the results to the evolution of major types of sexual reproduction, particularly simultaneous hermaphroditism. We find that complementarity strategies consistently evolve under a broad range of conditions, but that those most consistent with the simultaneous hermaphroditism can predominate only when a substantial cost of repeatedly adopting the female role is imposed. The cost is analogous to the fecundity reduction to be expected when a single partner must repeatedly produce the eggs in sexual reproduction.

Animals↗
PubMed1998

TCR transgenic mice in which usage of transgenic alpha- and beta-chains is highly dependent on the level of selecting ligand.

We have produced a TCR transgenic mouse that uses a TCR derived from a Th1 clone that is specific for residues 64 to 76 of the d allele of murine hemoglobin presented by I-Ek. Examination of these TCR transgenic mice on an H-2(k/k) background that expressed the nonstimulatory s allele of murine hemoglobin revealed that these mice express many endogenous TCR chains from both alpha and beta loci. We found that this transgenic TCR is also very inefficient at mediating beta selection, thereby showing a direct linkage between beta selection and allelic exclusion of TCR beta. We have also examined these mice on MHC backgrounds that have reduced levels of I-Ek and found that positive selection of cells with high levels of the transgenic TCR depends greatly on the ligand density. Decreasing the selecting ligand density is a means of reducing the number of available selecting niches, and the data reveal that the 3.L2 TCR is used sparingly for positive selection under conditions where the number of niches becomes limiting. The results, therefore, show a way that T cells may get to the periphery with two self-restricted TCRs: one that efficiently mediates positive selection, and another that is inefficient at positive selection with the available niches.

Animals↗
PubMed1998

In vivo expression of a TCR antagonist: T cells escape central tolerance but are antagonized in the periphery.

Transgenic 3.L2 T cells are stimulated by Hb(64-76)/I-Ek and are positively selected on I-Ek plus self-peptides. To this pool of self-peptides we have added a single, well-defined 3.L2 TCR antagonist (A72) in vivo. We find that mice expressing both the 3.L2 TCR and A72 have a minimal loss of T cells expressing the clonotypic TCR in the thymus and spleen. Importantly, the proliferative response of 3.L2 x A72 splenocytes is significantly reduced compared with splenocytes from 3.L2 mice. This reduced response can be attributed to peripheral antagonism. Thus we have identified a new class of self-ligands whose predominant effect is constitutive peripheral antagonism rather than negative selection. The net effect of these ligands is to avoid potential self-reactivity while maintaining as large a repertoire as possible.

Animals↗
PubMed1998

Specific single or double proline substitutions in the "spring-loaded" coiled-coil region of the influenza hemagglutinin impair or abolish membrane fusion activity.

We tested the role of the "spring-loaded" conformational change in the fusion mechanism of the influenza hemagglutinin (HA) by assessing the effects of 10 point mutants in the region of high coiled-coil propensity, HA2 54-81. The mutants included proline substitutions at HA2 55, 71, and 80, as well as a double proline substitution at residues 55 and 71. Mutants were expressed in COS or 293T cells and assayed for cell surface expression and structural features as well as for their ability to change conformation and induce fusion at low pH. We found the following: Specific mutations affected the precise carbohydrate structure and folding of the HA trimer. All of the mutants, however, formed trimers that could be expressed at the cell surface in a form that could be proteolytically cleaved from the precursor, HA0, to the fusion-permissive form, HA1-S-S-HA2. All mutants reacted with an antibody against the major antigenic site and bound red blood cells. Seven out of ten mutants displayed a wild-type (wt) or moderately elevated pH dependence for the conformational change. V55P displayed a substantial reduction (approximately 60- 80%) in the initial rate of lipid mixing. The other single mutants displayed efficient fusion with the same pH dependence as wt-HA. The double proline mutant V55P/ S71P displayed no fusion activity despite being well expressed at the cell surface as a proteolytically cleaved trimer that could bind red blood cells and change conformation at low pH. The impairment in fusion for both V55P and V55P/S71P was at the level of outer leaflet lipid mixing. We interpret our results in support of the hypothesis that the spring-loaded conformational change is required for fusion. An alternate model is discussed.

Animals↗
PubMed1998

Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses.

Herein we report the generation of mice lacking the ubiquitously expressed Janus kinase, Jak1. Jak1-/- mice are runted at birth, fail to nurse, and die perinatally. Although Jak1-/- cells are responsive to many cytokines, they fail to manifest biologic responses to cytokines that bind to three distinct families of cytokine receptors. These include all class II cytokine receptors, cytokine receptors that utilize the gamma(c) subunit for signaling, and the family of cytokine receptors that depend on the gp130 subunit for signaling. Our results thus demonstrate that Jak1 plays an essential and nonredundant role in promoting biologic responses induced by a select subset of cytokine receptors, including those in which Jak utilization was thought to be nonspecific.

Animals↗
PubMed1998

Vapor emissions resulting from Nd:YAG laser interaction with tooth structure.

UNLABELLED: The Neodymium:yttrium aluminum garnet (Nd:YAG) dental laser has been cleared by the United States Food and Drug Administration (FDA) for marketing in intraoral soft tissue treatment. The efficacy and safety of the Nd:YAG laser in the treatment of hard dental tissue as well as the effects of dental irradiation on the pulp and periodontium have been investigated. Odors resulting from laser irradiation have been reported, but the nature and toxicity of associated decomposition vapors is unknown and the health consequences of their inhalation have not yet been studied. OBJECTIVES: The purpose of this in vitro study was to identify vapors emitted during interaction of the Nd:YAG laser with carious human enamel and dentin and sound enamel and dentin coated with organic ink. METHODS: Vapor emissions were collected from prepared sections of extracted human teeth receiving laser irradiation of 100 mJ and 10 Hz for a duration of 1, 10, or 60 s. Emissions were collected by means of charcoal absorption tubes, and subsequently analyzed using a Gas Chromatograph equipped with Mass Selective (GC/MS) and Flame Ionization Detectors to identify the chemical constituents of the vapors. RESULTS: No compounds were identified in Nd:YAG laser-treated caries, enamel and dentin. No volatile vapors were identified from samples of tooth materials exposed to the laser for 1 or 10 s. Camphor was positively identified in the test sample which consisted of India ink-coated dentin and the reference sample of India ink-coated glass beads, both exposed to the laser for 60 s. 2,5-norbornadiene was tentatively identified in these samples. The Threshold Limit Value (TLV) of camphor is 2 ppm with a Lethal Dose Level (LDLo) of 50 mg/kg (human oral), while the TLV and LDLo of 2,5-norbornadiene is unknown. SIGNIFICANCE: Occupational and public health safety measures are discussed in this article. Further research is needed to quantify the compounds produced and to determine their toxicity to patients and to dental care providers.

Air Pollution, Indoor↗
PubMed1998

ADAMs: focus on the protease domain.

ADAMs are proteins containing a disintegrin and metalloproteinase domain. Several important insights were provided in the past year regarding ADAM metalloproteinases. ADAM 10 was implicated in the Notch signaling pathway. ADAM 17 was shown to be the long sought after tumor necrosis factor-alpha convertase and the crystal structure of its metalloproteinase domain was determined.

ADAM Proteins↗
PubMed1998

Therapeutic use of cannabis: clarifying the debate.

The debate regarding therapeutic use of cannabis is being confused by a lack of distinction between therapeutic and social use of cannabis. Separate consideration of therapeutic and social use would enable strategies to minimise any negative social impact of therapeutic use. For therapeutic use of cannabis to be considered on its own merits, greater emphasis needs to be placed on scientific evidence of therapeutic efficacy. At present the evidence is limited, it mostly relates to the use of synthetic cannabinoids, and much of it fails to compare cannabis with the best therapies available for the conditions of interest. Claims of therapeutic efficacy tend to be based on opinion and anecdote rather than the results of controlled studies. Further research is needed to clarify the potential therapeutic benefits, to enable claims of therapeutic use to be objectively assessed and to enable informed decisions to be made about the relative risks and benefits for any individual using cannabis for therapeutic purposes. Further research is required to clarify the efficacy of pure, synthetic cannabinoids compared to cannabis, the most effective route of administration, and the importance of delivering a known dose. The most likely value of cannabis is as an adjunct, rather than a replacement for, current medical approaches. The potential therapeutic benefits of cannabis will be greatest for those conditions where long-term cannabis use, with its attendant health risks, is not an issue and where the patient has the capacity to titrate dose against symptoms. There is sufficient evidence of potential therapeutic benefit to justify the facilitation of further research.

Journal Article↗
PubMed1998

Nd:YAG and CO2 laser therapy of oral mucosal lesions.

OBJECTIVE: Experiences gained in the management of oral mucosal lesions by CO2 and Nd:YAG laser therapy in an outpatient clinic treated over an 80-year period are described. SUMMARY BACKGROUND DATA: Lasers have indications for use in dentistry for incision, excision, and coagulation of intraoral soft tissue. Advances in laser technology have provided delivery systems for site-specific delivery of laser energy with short interaction items on tissue to be ablated. This study retrospectively evaluates a series of clinical case studies. METHODS: Sixty-four patients with a variety of benign oral soft tissue lesions were treated by laser excision. Thirty-five patients were treated by a pulsed fiberoptic delivered Nd:YAG contact laser, and 29 by a continuous free-beam CO2 non-contact laser. The largest group of lesions treated were leukoplakia (39 cases). Other lesions excised and biopsied were lichen planus, squamous papilloma, pyogenic granuloma, focal melanosis, nonhealing traumatic ulceration, hemangioma, and lymphangioma. All patients were followed postoperatively (mean 6.8 months, range 1-36 months). RESULTS: Laser excision was well tolerated by patients with no intraoperative or postoperative adverse effects. All patients healed postsurgically with no loss of function. CONCLUSIONS: CO2 and Nd:YAG lasers are successful surgical options when performing excision of benign intraoral lesions. Advantages of laser therapy include minimal postoperative pain, conservative site-specific minimally invasive surgeries, and elimination of need for sutures.

Adolescent↗