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Biomedical subjects

J M White

Publications and source records attributed to J M White.

At least 163 records · Page 9Linked to original sources
PubMed1994

Secretion of IL-4 from human basophils. The relationship between IL-4 mRNA and protein in resting and stimulated basophils.

Purified human basophils have been examined for secretion of IL-4 protein and expression of IL-4 mRNA after stimulation with several secretagogues. In general, these studies used a 15-min preincubation with IL-3, before challenge with secretagogues. Under these conditions, IL-4 release averaged 30 pg/10(6) basophils (range 4-70) after challenge with anti-IgE Ab. FMLP and C5a led to somewhat lower levels of secretion. A direct comparison of basophils at 88 to 99% purity with basophils from the same preparations, but at lower purities, showed that the amount of IL-4 secretion was proportional to the purity of the basophils. The presence of mRNA for IL-4 (as determined by reverse transcriptase-PCR, competitive reverse transcriptase-PCR, or Northern blots) was also strictly related to the purity of the basophils. IL-4 mRNA was also found to be constitutively present and was increased after stimulation. The concentration of polyclonal anti-IgE Ab required for optimal IL-4 release was somewhat less than that required for optimal histamine release. IL-4 secretion was slower (t1/2 of 1.5 h) than histamine release and was inhibited by cycloheximide. In a final series of studies, we found that IL-3 was not required for IL-4 secretion; a short 15-min preincubation with IL-3 resulted in the same or slightly less IL-4 release than no treatment with IL-3. In contrast, an 18-h pretreatment with IL-3 resulted in a nearly tenfold increase in IL-4 secretion. We conclude that human basophils secrete IL-4 in response to several secretagogues and that IL-3 priming is not necessary to observe IL-4 secretion.

Base Sequence↗
PubMed1994

Lipid-anchored influenza hemagglutinin promotes hemifusion, not complete fusion.

It has been proposed that membrane fusion events such as virus-cell fusion proceed through a hemifusion intermediate, a state where lipids but not contents of the fusing compartments mix. We engineered the influenza hemagglutinin (HA) such that it would be anchored in membranes via a glycosylphosphatidylinositol (GPI) tail. GPI-anchored HA forms a trimer that can bind red blood cells (RBCs) and change conformation under fusion-inducing conditions. Using RBCs labeled with fluorescent lipid or fluorescent soluble content probes, we found that GPI-anchored HA mediated lipid mixing with similar time course and efficiency as wt-HA, yet did not mediate transfer of soluble contents. Hence, GPI-anchored HA appears to initiate, but not complete, a fusion reaction. We interpret our results as evidence for uncoupling a physiological fusion reaction, for trapping a hemifusion intermediate, and for assigning a role to a transmembrane domain in a fusion event.

Base Sequence↗
PubMed1994

Twenty-four hour ambulatory monitoring of tremor, sweating, skin temperature and locomotor activity in the alcohol withdrawal syndrome.

An ambulatory monitor has been used to determine the characteristic patterns of tremor, sweating, skin temperature and locomotor activity in subjects undergoing alcohol withdrawal. Twenty-four hour records were obtained from six male subjects who had been consuming an average of 345 g of alcohol per day prior to cessation and from a group of age-matched controls. Consistent with earlier research and clinical observation, tremor, sweating and locomotor activity were elevated in withdrawal subjects. Sweating was greatest in the period from approximately 00.00 h to 06.00 h, as was skin temperature. Tremor and activity levels decreased during this period, but were considerably higher in withdrawal subjects. The data suggest that 24-h monitoring of alcohol withdrawal using objective methods provides a more sensitive assessment technique than the standard clinical approaches. The technique may be of value in other dysautonomic states.

Adult↗
PubMed1994

Saccades to remembered target locations: an analysis of systematic and variable errors.

We studied the effects of varying delay interval on the accuracy and velocity of saccades to the remembered locations of visual targets. Remembered saccades were less accurate than control saccades. Both systematic and variable errors contributed to the loss of accuracy. Systematic errors were similar in size for delay intervals ranging from 400 msec to 5.6 sec, but variable errors increased monotonically as delay intervals were lengthened. Compared to control saccades, remembered saccades were slower and the peak velocities were more variable. However, neither peak velocity nor variability in peak velocity was related to the duration of the delay interval. Our findings indicate that a memory-related process is not the major source of the systematic errors observed on memory trials.

Animals↗
PubMed1994

The effects of GABAB ligands on alcohol withdrawal in mice.

Recent research suggests that the GABAB receptor may mediate some of the acute effects of alcohol, but little is known of its involvement in alcohol withdrawal. Mice made dependent on alcohol exhibited tremor and tail arch when consumption ceased. Diazepam dose-dependently attenuated both tremor and tail arch, whereas baclofen had no effect on either of these two withdrawal symptoms. However, baclofen dose-dependently induced convulsant behaviour in the withdrawing mice, and this was significantly attenuated by the GABAB antagonists phaclofen (50 mg/kg) and CGP 35348 (300 mg/kg), but not BPBA (50 mg/kg). Phaclofen, BPBA, and CGP 35348, when administered alone and in combination with a single dose of baclofen, did have an effect on tremor, although the magnitude was small in comparison to that seen with diazepam. It appears that the GABAB receptor may play a role in mediating convulsions during alcohol withdrawal, and that in this system baclofen is proconvulsant.

Animals↗
PubMed1994

Injecting behaviour and risky needle use amongst methadone maintenance clients.

The injecting behaviour and risky needle use of a sample of 193 methadone maintenance clients was investigated. The majority of the sample (n = 116) reported injecting one or more drugs in the month prior to data collection. Compared with non-injectors, the injectors were slightly younger, had been on the methadone program for a shorter period of time, had lower methadone doses and more severe drug and legal problems. The injecting sub-group was examined in more detail by comparing those subjects whose injecting practices conformed to guidelines on minimizing risk of HIV transmission with those who, in the preceding month, made at least one injection contravening these guidelines and thus placed themselves at risk of contracting HIV. A greater proportion of these risky injectors were unemployed. Importantly, risky injectors had lesser knowledge of means of preventing the spread of HIV than safe injectors. It is concluded that the reduction of HIV transmission could be enhanced by improvements in methadone programs, particularly ensuring adequate dosing and high retention rates. Further, there is a need to improve knowledge with regard to what are safe and what are risky injecting practices and needle/syringe cleaning methods.

Adult↗
PubMed1994

Computerized handwriting instruction with severely mentally handicapped adults.

The effectiveness of computerized handwriting instruction incorporating modelling of the target letter, corrective feedback and reinforcement contingent upon letter accuracy was examined with severely mentally retarded adults. Assisted by faded prompts on a sheet of paper, subjects wrote the letter 'q' while their handwriting patterns were detected by a digitized graphics tablet linked to a computer. Computerized instruction was introduced for six subjects (mean mental age = 3 years, 10 months) according to a multiple-baseline-across-subjects design. Instruction produced significant improvements in letter quality which were not simply due to the effects of practice. Subjects who had extended practice before being introduced to the computer were less responsive to the information provided by the computer and did not attain the levels of performance accuracy achieved by other subjects.

Adult↗
PubMed1994

Novel surface attachment mechanism of the Streptococcus pneumoniae protein PspA.

Pneumococcal surface protein A (PspA) of Streptococcus pneumoniae has been found to utilize a novel mechanism for anchoring to the bacterial cell surface. In contrast to that of surface proteins from other gram-positive bacteria, PspA anchoring required choline-mediated interactions between the membrane-associated lipoteichoic acid and the C-terminal repeat region of PspA. Release of PspA from the cell surface could be effected by deletion of 5 of the 10 C-terminal repeat units, by high concentrations of choline, or by growth in choline-deficient medium. Other pneumococcal proteins, including autolysin, which has a similar C-terminal repeat region, were not released by these treatments. The attachment mechanism utilized by PspA thus appears to be uniquely adapted to exploit the unusual structure of the pneumococcal cell surface. Further, it has provided the means for rapid and simple isolation of immunogenic PspA from S. pneumoniae.

Amino Acid Sequence↗
PubMed1994

The receptor for the subgroup A avian leukosis-sarcoma viruses binds to subgroup A but not to subgroup C envelope glycoprotein.

The putative subgroup A avian leukosis-sarcoma virus (ALSV) receptor (Tva) was recently cloned by gene transfer (P. Bates, J. A. Young, and H. E. Varmus, Cell 74:1043-1051, 1993; J. A. T. Young, P. Bates, and H. E. Varmus, J. Virol. 67:1811-1816, 1993). Susceptibility to infection by subgroup A ALSV is conferred on cells upon transfection with cDNAs encoding tva. The hypothesis that tva encodes a specific receptor for subgroup A ALSV predicts that the Tva protein should bind to subgroup A, but not to subgroup C, envelope glycoprotein. In this study, we examined this prediction by using several biochemical assays. We established stable NIH 3T3 cell lines expressing either Tva, the subgroup A envelope glycoprotein (Env-A), or the subgroup C envelop glycoprotein (Env-C) and used them in conjunction with soluble forms of these molecules to demonstrate specific binding. When cell lysates containing Tva were mixed with lysates of either Env-A or Env-C, an immunoprecipitable complex formed between Tva and Env-A but not between Tva and Env-C. A soluble, oligomeric form, of Env-A, not Env-C, binds to cells expressing Tva. Reciprocally, a secreted form of Tva can bind to cells expressing Env-A but not to cells expressing Env-C. A specific and stable complex formed between soluble Env-A and secreted Tva as demonstrated by sucrose density gradient centrifugation. Thus, by three kinds of assays, Tva appears to bind specifically to Env-A, which is consistent with genetic evidence that it serves as the cell surface receptor of subgroup A ALSV and the main determinant of subgroup specificity.

3T3 Cells↗
PubMed1994

Sterilization of teeth by gamma radiation.

Clinical simulations and restorative materials research and development conducted in vitro require the use of large numbers of extracted teeth. The simultaneous need for infection control procedures and minimal alterations of structure and properties of the tissue prompted this study of gamma irradiation as a method to eliminate microbes associated with extracted teeth and their storage solutions. Evaluations of potential change in structure of dentin were conducted in terms of permeability, Fourier transform infrared spectroscopy (FTIR), and optical properties. The dose required for sterilization by gamma irradiation was established by means of a tooth model inoculated with Bacillus subtilis (10(8) organisms/mL). Sterilization occurred at a dose above 173 krad with use of a Cesium (Cs137) radiation source. Gamma irradiation did not affect permeability of crown segments of dentin. A comparative evaluation of the effects of four sterilization methods on dentin disks was based on FTIR and ultraviolet-visible-near infrared (UV/VIS/NIR) spectra before and after sterilization by (1) gamma irradiation; (2) ethylene oxide; (3) dry heat; and (4) autoclaving. No detectable changes were found with gamma irradiation, but all other methods introduced some detectable change in the spectra. This suggests that common methods of sterilization alter the structure of the dentin, but gamma irradiation shows promise as a method which both is effective and introduces no detectable changes as measured by FTIR, UV/VIS/NIR, or permeability.

Bacteria↗
PubMed1994

Intrapulpal temperatures during pulsed Nd:YAG laser treatment of dentin, in vitro.

Lasers are being used for soft tissue removal, caries removal, and treatment of root surface sensitivity. One concern for laser safety is that the heat produced at the irradiated root surface may diffuse to the pulp causing irreversible pulpal damage. To test this heat diffusion, copper-constantan thermocouples were inserted into the radicular pulp canals of extracted teeth. Simulating direct exposure which might occur during gingival excision, superficial caries removal, and modification of the dentin surface for treatment of root surface sensitivity, a 2 mm2 area of the external root surface was uniformly irradiated with a pulsed Nd:YAG laser using a 320 microns diameter fiber optic contact probe. Power was varied from 0.3 to 3.0 W with frequencies of 10 and 20 Hz. Temperature changes during cavity preparations using a high speed handpiece with air coolant were also recorded. Repeated measures ANOVA (P < or = 0.05) indicated that intrapulpal temperatures increased as a function of power, frequency, and time. Intrapulpal temperatures decreased as remaining dentin thickness (0.2 to 2.0 mm) increased for each laser parameter. Irradiation of dentin using a Nd:YAG pulsed laser, within the treatment times, powers, and frequencies with adequate remaining dentin thickness, as outlined in this paper, should not cause devitalizing intrapulpal temperature rises.

Analysis of Variance↗
PubMed1994

Soft tissue anchor systems.

The concept of soft tissue attachment and reattachment has been addressed over the years through a variety of surgical techniques. This includes tendons and ligaments that have been detached both surgically and traumatically from their osseous origins or insertions. This study is designed to provide the reader with a comprehensive overview of current commercially available devices. Detailed descriptions of the various devices are provided along with a discussion of the advantages and disadvantages of each. Their application and use in reconstructive foot and ankle surgery are also discussed.

Ankle↗
PubMed1993

The precursor region of a protein active in sperm-egg fusion contains a metalloprotease and a disintegrin domain: structural, functional, and evolutionary implications.

PH-30, a sperm surface protein involved in sperm-egg fusion, is composed of two subunits, alpha and beta, which are synthesized as precursors and processed, during sperm development, to yield the mature forms. The mature PH-30 alpha/beta complex resembles certain viral fusion proteins in membrane topology and predicted binding and fusion functions. Furthermore, the mature subunits are similar in sequence to each other and to a family of disintegrin domain-containing snake venom proteins. We report here the sequences of the PH-30 alpha and beta precursor regions. Their domain organizations are similar to each other and to precursors of snake venom metalloproteases and disintegrins. The alpha precursor region contains, from amino to carboxyl terminus, pro, metalloprotease, and disintegrin domains. The beta precursor region contains pro and metalloprotease domains. Residues diagnostic of a catalytically active metalloprotease are present in the alpha, but not the beta, precursor region. We propose that the active sites of the PH-30 alpha and snake venom metalloproteases are structurally similar to that of astacin. PH-30, acting through its metalloprotease and/or disintegrin domains, could be involved in sperm development as well as sperm-egg binding and fusion. Phylogenetic analysis indicates that PH-30 stems from a multidomain ancestral protein.

ADAM Proteins↗