PubMed Health⌕ Search

Biomedical subjects

L J White

Publications and source records attributed to L J White.

At least 19 recordsLinked to original sources
PubMed2001

The structural identifiability and parameter estimation of a multispecies model for the transmission of mastitis in dairy cows.

A structural identifiability analysis is performed on a mathematical model for the coupled transmission of two classes of pathogen. The pathogens, classified as major and minor, are aetiological agents of mastitis in dairy cows that interact directly and via the immunological reaction in their hosts. Parameter estimates are available from experimental data for all but four of the parameters in the model. Data from a longitudinal study of infection are used to estimate these unknown parameters. A novel approach and application of structural identifiability analysis is combined in this paper with the estimation of cross-protection parameters using epidemiological data.

Animals↗
PubMed2001

Refractive changes caused by hypoxia after laser in situ keratomileusis surgery.

OBJECTIVE: To determine whether hypoxia induces refractive changes in subjects who have had laser in situ keratomileusis (LASIK) refractive surgery. DESIGN: Prospective paired eye clinical trial. PARTICIPANTS: There were 20 LASIK subjects (40 eyes) and 20 myopic non-LASIK controls (40 eyes). INTERVENTION: Each subject had one eye exposed to ocular surface hypoxia (humidified nitrogen) by use of an airtight goggle system at sea level for 2 hours. The other eye was simultaneously exposed to humidified, compressed air (21% oxygen) with the same airtight goggle system. MAIN OUTCOME MEASURES: Keratometry, cycloplegic refraction, and pachymetry were compared before and after exposure by use of repeated measures analysis of variance. RESULTS: A significant myopic shift (P: < 0.01) occurred in LASIK corneas exposed to hypoxia compared with myopic control subjects. A significant increase in corneal thickening occurred symmetrically in both LASIK and control subjects exposed to hypoxia. There was a trend toward corneal steepening (keratometry) in LASIK subjects, but this was not statistically significant. CONCLUSIONS: These results suggest that ocular surface hypoxia induces a myopic shift in LASIK subjects.

Adult↗
PubMed2001

A multispecies model for the transmission and control of mastitis in dairy cows.

Mastitis in dairy cows is a significant economic and animal welfare issue in the dairy industry. The bacterial pathogens responsible for infection of the mammary gland may be split into two main categories: major and minor pathogens. Infection with major pathogens generally results in clinical illness or strong inflammatory responses and reduced milk yields, whereas minor pathogen infection is usually subclinical. Previous investigations have considered the transmission of these pathogens independently. Experimental evidence has shown cross-protection between species of pathogens. In this study a mathematical model for the coupled transmission of major and minor pathogens along with their interaction via the host was developed in order to consider various methods for controlling the incidence of major pathogen infection. A stability analysis of the model equilibria provides explanations for observed phenomena and previous decoupled modelling results. This multispecies model structure has provided a basis for quantifying the extent of cross-protection between species and assessing possible control strategies against the disease.

Animals↗
PubMed2001

Mapping microbial biodiversity.

We report the development of a prototype database that "maps" microbial diversity in the context of the geochemical and geological environment and geographic location. When it is fully implemented, scientists will be able to conduct database searches, construct maps containing the information of interest, download files, and enter data over the Internet.

Databases, Factual↗
PubMed2001

Wild Mandrillus sphinx are carriers of two types of lentivirus.

Mandrillus sphinx, a large primate living in Cameroon and Gabon and belonging to the Papionini tribe, was reported to be infected by a simian immunodeficiency virus (SIV) (SIVmndGB1) as early as 1988. Here, we have identified a second, highly divergent SIVmnd (designated SIVmnd-2). Genomic organization differs between the two viral types; SIVmnd-2 has the additional vpx gene, like other SIVs naturally infecting the Papionini tribe (SIVsm and SIVrcm) and in contrast to the other SIVmnd type (here designated SIVmnd-1), which is more closely related to SIVs infecting l'hoest (Cercopithecus lhoesti lhoesti) and sun-tailed (Cercopithecus lhoesti solatus) monkeys. Importantly, our epidemiological studies indicate a high prevalence of both types of SIVmnd; all 10 sexually mature wild-living monkeys and 3 out of 17 wild-born juveniles tested were infected. The geographic distribution of SIVmnd seems to be distinct for the two types: SIVmnd-1 viruses were exclusively identified in mandrills from central and southern Gabon, whereas SIVmnd-2 viruses were identified in monkeys from northern and western Gabon, as well as in Cameroon. SIVmnd-2 full-length sequence analysis, together with analysis of partial sequences from SIVmnd-1 and SIVmnd-2 from wild-born or wild-living mandrills, shows that the gag and pol regions of SIVmnd-2 are closest to those of SIVrcm, isolated from red-capped mangabeys (Cercocebus torquatus), while the env gene is closest to that of SIVmnd-1. pol and env sequence analyses of SIV from a related Papionini species, the drill (Mandrillus leucophaeus), shows a closer relationship of SIVdrl to SIVmnd-2 than to SIVmnd-1. Epidemiological surveys of human immunodeficiency virus revealed a case in Cameroon of a human infected by a virus serologically related to SIVmnd, raising the possibility that mandrills represent a viral reservoir for humans similar to sooty mangabeys in Western Africa and chimpanzees in Central Africa.

Amino Acid Sequence↗
PubMed2001

Role of alpha/beta interferon in Venezuelan equine encephalitis virus pathogenesis: effect of an attenuating mutation in the 5' untranslated region.

Venezuelan equine encephalitis virus (VEE) is an important equine and human pathogen of the Americas. In the adult mouse model, cDNA-derived, virulent V3000 inoculated subcutaneously (s.c.) causes high-titer peripheral replication followed by neuroinvasion and lethal encephalitis. A single change (G to A) at nucleotide 3 (nt 3) of the 5' untranslated region (UTR) of the V3000 genome resulted in a virus (V3043) that was avirulent in mice. The mechanism of attenuation by the V3043 mutation was studied in vivo and in vitro. Kinetic studies of virus spread in adult mice following s.c. inoculation showed that V3043 replication was reduced in peripheral organs compared to that of V3000, titers in serum also were lower, and V3043 was cleared more rapidly from the periphery than V3000. Because clearance of V3043 from serum began 1 to 2 days prior to clearance of V3000, we examined the involvement of alpha/beta interferon (IFN-alpha/beta) activity in VEE pathogenesis. In IFN-alpha/betaR(-/-) mice, the course of the wild-type disease was extremely rapid, with all animals dying within 48 h (average survival time of 30 h compared to 7.7 days in the wild-type mice). The mutant V3043 was as virulent as the wild type (100% mortality, average survival time of 30 h). Virus titers in serum, peripheral organs, and the brain were similar in V3000- and V3043-infected IFN-alpha/betaR(-/-) mice at all time points up until the death of the animals. Consistent with the in vivo data, the mutant virus exhibited reduced growth in vitro in several cell types except in cells that lacked a functional IFN-alpha/beta pathway. In cells derived from IFN-alpha/betaR(-/-) mice, the mutant virus showed no growth disadvantage compared to the wild-type virus, suggesting that IFN-alpha/beta plays a major role in the attenuation of V3043 compared to V3000. There were no differences in the induction of IFN-alpha/beta between V3000 and V3043, but the mutant virus was more sensitive than V3000 to the antiviral actions of IFN-alpha/beta in two separate in vitro assays, suggesting that the increased sensitivity to IFN-alpha/beta plays a major role in the in vivo attenuation of V3043.

5' Untranslated Regions↗
PubMed2001

Histological findings in the prostate two years following cryosurgical ablation.

We examined the pathological findings from prostatic whole mounts obtained at post-mortem, 2 years following cryosurgical ablation of the prostate (CSAP), to evaluate the presence or absence of residual benign or malignant tissue. Whole prostates were obtained from two patients at post-mortem, in which the cause of death was not related to prostate cancer. The patients had received CSAP 24 and 30 months earlier, as the primary treatment for prostate cancer. Complete ablation of the gland was demonstrated in one case, with some residual viable benign glands in the transitional zone in the second case. These results suggest that localized prostate cancer can be successfully eradicated by CSAP.

Autopsy↗
PubMed2000

Perceived continuity and pitch perception.

Three experiments investigated the importance of perceived stimulus continuity for the perception of the fundamental frequency (F0) of an unresolved complex tone. The F0 of the complex was 250 Hz and the harmonics were bandpass filtered between 5500 and 7500 Hz. In the first experiment, F0 discrimination was measured for single-burst tones with durations of 20, 40, and 80 ms, and for stimuli containing two 20- or 40-ms tone bursts separated by an 8- or 16-ms gap. For the single-burst conditions, there was a large decrease in threshold as the duration was increased from 20 to 40 ms. However, performance in the gapped conditions was much worse than that for the single-burst condition with the same cumulative duration (e.g., two 20-ms bursts separated by 8 ms produced higher thresholds than one 40-ms burst). Adding a bandpass noise (with the same spectral envelope as the tone) in the gap between the two tone bursts improved performance to the level of the single-burst condition. When the noise was added, the two discrete tone bursts were perceived as one single tone burst interrupted by the noise, and this seemed to facilitate discrimination. In a second experiment, the effects on pitch of an envelope delay (phase shift) of 0.75 periods between two tone bursts separated by an 8-ms gap were investigated. If the gap was silent, the pitch of the pair was unaffected by the phase shift. However, if the gap contained the bandpass noise, the phase shift between the bursts did produce a significant downward shift in the pitch of the pair. Finally, the third experiment showed that presenting a noise before a single 20-ms burst may improve discrimination performance in some listeners, but not sufficiently to account for the results of the first experiment purely in terms of an improvement in the discriminability of the second tone burst in the pair. The experiments suggest that a level decrease between two tone bursts may disrupt or reset a long integration mechanism, decreasing performance. When there is no level decrease between the bursts, the auditory system may assume that the two bursts belong to the same single tone and analyze them together in order to derive F0.

Adult↗
PubMed2000

Pitch matches between unresolved complex tones differing by a single interpulse interval.

The experiment compared the pitches of complex tones consisting of unresolved harmonics. The fundamental frequency (F0) of the tones was 250 Hz and the harmonics were bandpass filtered between 5500 and 7500 Hz. Two 20-ms complex-tone bursts were presented, separated by a brief gap. The gap was an integer number of periods of the waveform: 0, 4, or 8 ms. The envelope phase of the second tone burst was shifted, such that the interpulse interval (IPI) across the gap was reduced or increased by 0.25 or 0.75 periods (1 or 3 ms). A "no shift" control was also included, where the IPI was held at an integer number of periods. Pitch matches were obtained by varying the F0 of a comparison tone with the same temporal parameters as the standard but without the shift. Relative to the no-shift control, the variations in IPI produced substantial pitch shifts when there was no gap between the bursts, but little effect was seen for gaps of 4 or 8 ms. However, for some conditions with the same IPI in the shifted interval, an increase in the IPI of the comparison interval from 4 to 8 ms (gap increased from 0 to 4 ms) changed the pitch match. The presence of a pitch shift suggests that the pitch mechanism is integrating information across the two tone bursts. It is argued that the results are consistent with a pitch mechanism employing a long integration time for continuous stimuli that is reset in response to temporal discontinuities. For a 250-Hz F0, an 8-ms IPI may be sufficient for resetting. Pitch models based on a spectral analysis of the simulated neural spike train, on an autocorrelation of the spike train, and on the mean rate of pitch pulses, all failed to account for the observed pitch matches.

Adult↗
PubMed2000

Norwalk virus open reading frame 3 encodes a minor structural protein.

Norwalk virus (NV) is a causative agent of acute epidemic nonbacterial gastroenteritis in humans. The inability to cultivate NV has required the use of molecular techniques to examine the genome organization and functions of the viral proteins. The function of the NV protein encoded by open reading frame 3 (ORF 3) has been unknown. In this paper, we report the characterization of the NV ORF 3 protein expressed in a cell-free translation system and in insect cells and show its association with recombinant virus-like particles (VLPs) and NV virions. Expression of the ORF 3 coding region in rabbit reticulocyte lysates resulted in the production of a single protein with an apparent molecular weight of 23,000 (23K protein), which is not modified by N-linked glycosylation. The ORF 3 protein was expressed in insect cells by using two different baculovirus recombinants; one recombinant contained the entire 3' end of the genome beginning with the ORF 2 coding sequences (ORFs 2+3), and the second recombinant contained ORF 3 alone. Expression from the construct containing both ORF 2 and ORF 3 resulted in the expression of a single protein (23K protein) detected by Western blot analysis with ORF 3-specific peptide antisera. However, expression from a construct containing only the ORF 3 coding sequences resulted in the production of multiple forms of the ORF 3 protein ranging in size from 23,000 to 35,000. Indirect-immunofluorescence studies using an ORF 3 peptide antiserum showed that the ORF 3 protein is localized to the cytoplasm of infected insect cells. The 23K ORF 3 protein was consistently associated with recombinant VLPs purified from the media of insect cells infected with a baculovirus recombinant containing the entire 3' end of the NV genome. Western blot analysis of NV purified from the stools of NV-infected volunteers revealed the presence of a 35K protein as well as multiple higher-molecular-weight bands specifically recognized by an ORF 3 peptide antiserum. These results indicate that the ORF 3 protein is a minor structural protein of the virion.

Animals↗
PubMed2000

Extraprostatic biopsy improves the staging of localized prostate cancer.

OBJECTIVE: To evaluate the role and safety of biopsy of the seminal vesicles and neurovascular bundles in determining the pathologic stage of prostatic carcinoma. METHODS: Eighty-one consecutive patients were enrolled in a comprehensive cryosurgical biopsy protocol that included sextant intraprostatic plus extraprostatic biopsy. The pathologic stage, determined after biopsy, was compared with the clinical stage, determined by digital rectal examination (DRE) and transrectal ultrasonographic (TRUS) evaluation. As well, complication rates for these patients were compared with rates for a separate group that underwent sextant intraprostatic biopsy alone. RESULTS: Of the 81 patients, 61 (75%) were confirmed to have cancer by biopsy. None of these patients was considered to have extraprostatic extension by clinical evaluation (DRE and TRUS), but 16 of 61 (26%) were identified to have extraprostatic cancer in the seminal vesicles (8 of 61, 13%) or in the neurovascular bundles (8 of 61, 13%) by extraprostatic biopsy. There was no significant difference in the complication rates between sextant intraprostatic biopsy and sextant intraprostatic plus extraprostatic biopsy (p>0.97). CONCLUSIONS: Extraprostatic biopsy identifies extension of carcinoma in a large proportion of patients in whom clinical evaluation by DRE and TRUS indicates organ-confined disease. Extraprostatic biopsy is therefore warranted as routine evaluation before surgery in order to correctly stage prostatic carcinoma and select appropriate therapy.

Adult↗
PubMed1998

Microparasite population dynamics and continuous immunity.

A mathematical model is presented for the transmission of a microparasite where the hosts occupy one of two states, uninfected or infected. In each state, the hosts are distributed over a continuous range of immunity. The immune levels vary within hosts due to the processes of waning of immunity (when uninfected), and increasing immunity (when infected), eventually resulting in recovery. Immunity level also influences the host's ability to infect or be infected. Thus the proposed model incorporates both inter- and intra-host dynamics. It is shown from equilibrium results that this model is a general form of the susceptible-infected-resistant (SIR) and susceptible-infected-susceptible (SIS) family of models, a development that is useful for exploring multistrain pathogen transmission and use of vaccines which confer temporary protection.

Animals↗
PubMed1998

The etiology of refractive changes at high altitude after radial keratotomy. Hypoxia versus hypobaria.

OBJECTIVE: Refractive changes at high altitude that occur after radial keratotomy (RK) may be caused by hypoxia or hypobaria. DESIGN: A prospective study was performed to evaluate the effects of hypoxia on RK and non-RK corneas. PARTICIPANTS: There were 20 RK and 20 control eyes. INTERVENTION: These eyes were subjected to ocular surface hypoxia using an air-tight goggle system at sea level for 2 hours. MAIN OUTCOME MEASURES: Keratometry, cycloplegic refraction, and pachymetry were evaluated using repeated measures analysis of variance. RESULTS: A significant hyperopic shift (P < 0.0001) and corneal flattening (P < 0.0013) occurred in all subjects with RK compared with those of control subjects. Corneal thickening occurred symmetrically in both groups. CONCLUSIONS: These results suggest that refractive changes in subjects with RK occur at high altitude as a direct result of corneal hypoxia.

Adult↗
PubMed1998

A double-blind comparison between oral pseudoephedrine and topical oxymetazoline in the prevention of barotrauma during air travel.

To determine the efficacy of two decongestants (oral pseudoephedrine versus topical oxymetazoline) in the prevention of middle ear barotrauma during air travel, 150 adult volunteers with a history of ear pain during air travel were entered into a randomized, double-blind study conducted at two commercial airports. Each subject received 120 mg pseudoephedrine, oxymetazoline hydrochloride (0.05%), or a double placebo (capsule and nasal spray) administered 30 minutes before flight departure. After arrival at their final destinations, volunteers were asked to complete a questionnaire and return it by mail to investigators. Questions included the intensity and duration of otologic symptoms experienced while flying and possible drug side effects. A total of 124 subjects completed the study; 41 received 120 mg of pseudoephedrine, 42 received oxymetazoline nasal spray, and 41 received a double placebo (capsule and nasal spray). The three treatment groups were similar with regard to age, sex, medical history, and flight profile. Symptoms of barotrauma were reported by 34% of those receiving pseudoephedrine versus 71% of the control group, for a relative risk reduction of 52% (95% confidence interval [CI] 33% to 71%). In contrast, 64% of the oxymetazoline group reported symptoms of barotrauma, for a relative risk reduction of 10% (95% CI, 3% to 17%). These results suggest that treatment with 120 mg pseudoephedrine at least 30 minutes before flying appears to decrease the incidence of barotrauma. Oxymetazoline nasal spray is little more effective than placebo in reducing ear pain and discomfort associated with changing ambient pressures.

Administration, Intranasal↗
PubMed1998

Temporal processing of the pitch of complex tones.

The effect of tone duration on fundamental frequency (F0) discrimination is greater for complexes containing unresolved harmonics than for those containing resolved harmonics [Plack and Carlyon, J. Acoust. Soc. Am. 98, 1355-1364 (1995)]. Three experiments explored this effect further. The first experiment measured sensitivity (as d') to fundamental frequency (F0) differences for two complexes, both with an F0 of 250 Hz. The first complex was low-pass filtered at 1875 Hz to create a resolved complex and the second was bandpass filtered between 5500 and 7500 Hz to create an unresolved complex. The harmonics for the resolved complex were selected so that no two harmonics were the same between the two observation intervals. Performance for both complexes was measured for tone durations of 20, 40, 80, and 160 ms. For the unresolved complex, the effect of duration was greater than that for the resolved complex and greater than the predictions of a "multiple-looks" model assuming either peripheral (before sampling) or central (after combining samples) sources of variance. The second experiment replicated these results using an F0 of 62.5 Hz with the cutoff frequencies of the bandpass filters divided by four, confirming that the effect is related to resolvability and not to spectral region. In the final experiment, F0 discrimination for pairs of complexes separated by a temporal gap was measured relative to that for one complex. Performance for the resolved and unresolved complexes was similar: Very little effect of gap duration was observed and the results were consistent with the predictions of the peripheral-variance multiple-looks model. Taken together, the results suggest that the pitch mechanism for resolved harmonics uses a relatively short sampling window of around 20 ms, while the mechanism for unresolved harmonics may use a more complex strategy for optimizing the combination of information over time, perhaps involving a flexible integration time.

Adult↗
PubMed1998

Cross immunity and vaccination against multiple microparasite strains.

We explore the equilibrium properties of a series of compartmental, ODE models describing the interaction between different strains of pathogen. The interaction is conceptualized as acting through shared antigens: infection and recovery from one strain leaves the host with a primed immune response against subsequent strains. The models consider the effect of this priming on susceptibility (the ability to be infected) and transmission (the ability to infect) in an SIR model. In these models, the specific past history of infection is encapsulated in different susceptible compartments within the model. In a third, SIS, model, specific past history is not included, but strains have differential abilities to infect previously infected hosts. Equilibrium results include criteria for the coexistence of strains. For the SIR models, the region of coexistence defined by parameters shrinks as the effect of strains on each other (increased antigenic similarity) increases. For the SIS model, coexistence depends critically on the rate at which complete susceptibility is recovered following infection, and coexisting strains must have differential abilities to infect completely and partially susceptible hosts. Interestingly, this model provides analogies to commensalism (the first species gains from the presence of the second; the second neither gains nor loses from the interaction) and symbiosis (the presence of both species benefits the other). Additionally, we show that the maximum number of coexisting strains is two in this model. The effect of vaccination depends on the initial strain structure, the ability of vaccination to mount protection to both strains and the coverage. Vaccination may allow a previously excluded strain to coexist or exist alone, and may allow a previously rarer strain to become more common with the possibility of increasing incidence of disease. We discuss the dynamics of these models, compare model results to observed patterns and consider additional model structures. The importance of these results to specific multi-strain pathogens, in particular rotavirus, is considered.

Animals↗
PubMed1997

Inhibition of apoptosis in a human pre-B-cell line by CD23 is mediated via a novel receptor.

Human CD23 is a 45-kD type II membrane glycoprotein, which functions as a low-affinity receptor for IgE and as a ligand for the CD21 and CD11b/CD11c differentiation antigens. CD23 is released from the surface of cells as soluble fragments, and a 25-kD species of soluble CD23 (sCD23) appears to act as a multifunctional cytokine. In this report, sCD23 is shown to sustain the growth of low cell density cultures of a human pre-B-acute lymphocytic leukemia cell line, SMS-SB: no other cytokine tested was able to induce this effect. Flow cytometric analysis indicates that sCD23 acts to prevent apoptosis of SMS-SB cells. SMS-SB cells cultured at low cell density possess low levels of bcl-2 protein. Addition of sCD23 to cells at low cell density maintained bcl-2 expression at levels equivalent to those observed in SMS-SB cells cultured at higher cell densities. No CD23 mRNA was found in SMS-SB cells, ruling out an autocrine function for CD23 in this cell line model. Although SMS-SB cells do not express the known receptors for CD23, namely CD21, CD11b-CD18, or CD11c-CD18, the cells specifically bind CD23-containing liposomes, but not glycophorin-containing liposomes. Binding of CD23-containing liposomes is inhibited by anti-CD23 but not by anti-CD21 or anti-CD11b/c monoclonal antibodies. The data show that sCD23 prevents apoptosis of the SMS-SB cell line by acting through a novel receptor.

Apoptosis↗