Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 19 recordsLinked to original sources

PubMed2006

Indoor air quality risk factors for severe lower respiratory tract infections in Inuit infants in Baffin Region, Nunavut: a pilot study.

Inuit infants have extremely high rates of lower respiratory tract infection (LRTI), but the causes for this are unclear. The aims of this study were to assess, in young Inuit children in Baffin Region, Nunavut, the feasibility of an epidemiologic study of the association between indoor air quality (IAQ) and respiratory health; to obtain data on IAQ in their housing; and to identify and classify risk factors for LRTI. Twenty houses in Cape Dorset, Nunavut with children below 2 years of age, were evaluated using a structured housing inspection and measurement of IAQ parameters, and a respiratory health questionnaire was administered. Twenty-five percent of the children had, at some time, been hospitalized for chest illness. Houses were very small, and had a median of six occupants per house. Forty-one percent of the houses had a calculated natural air change rate <0.35 air changes per hour. NO(2) concentrations were within the acceptable range. Smokers were present in at least 90% of the households, and nicotine concentrations exceeded 1.5 microg/m(3) in 25% of the dwellings. Particulates were found to be correlated closely with nicotine but not with NO(2) concentrations, suggesting that their main source was cigarette smoking rather than leakage from furnaces. Mattress fungal levels were markedly increased, although building fungal concentrations were low. Dust-mites were virtually non-existent. Potential risk factors related to IAQ for viral LRTI in Inuit infants were observed in this study, including reduced air exchange and environmental tobacco smoke exposure. Severe lower respiratory tract infection is common in Inuit infants. We found reduced air change rates and high occupancy levels in houses in Cape Dorset, which may increase the risk of respiratory infections. This suggests the measures to promote better ventilation or more housing may be beneficial. Further health benefits may be obtained by reducing bed sharing by infants and greater turnover of mattresses, which were found to have high levels of fungi.

Air Pollutants↗

PubMed2005

Insomnia following hypocretin2-saporin lesions of the substantia nigra.

The neuropeptide hypocretin, also known as orexin, has been implicated in waking since its deletion leads to the sleep disorder narcolepsy. Hypocretin neurons project to major arousal areas, and in an effort to determine which region is responsible for the changes in sleep-wake architecture we have developed the neurotoxin hypocretin2-saporin, which lesions hypocretin receptor bearing neurons. Here, in rats, we investigate the effects of hypocretin2-saporin lesions of the substantia nigra and ventral tegmental area in the regulation of sleep and wakefulness. Bilateral injection of hypocretin2-sap into both the ventral tegmental area and substantia nigra (92 and 184 ng/microl, 0.25 microl in the ventral tegmental area and 0.5 microl in the substantia nigra) or into the substantia nigra alone (184 ng/microl, 0.5 microl) produced insomnia. The insomnia seemed to be associated with a large increase in locomotion on days 4 and 6 postinjection, as hyperactivity and stereotypic movements were consistently observed on the video recordings in all lesioned rats. In these rats, a nearly complete loss of both tyrosine hydroxylase and neuron-specific nuclear protein (neuronal nuclei) immunoreactive cells in the substantia nigra as well as diminution of tyrosine hydroxylase-immunoreactive fibers in the caudate putamen was found. Following bilateral injection of hypocretin2-sap at a lower concentration (46 ng/microl, 0.25 microl in the ventral tegmental area and 0.5 microl in the substantia nigra), very little reduction in the number of tyrosine hydroxylase- and neuronal nuclei-immunoreactive neurons and only a temporary increase in wakefulness (17.4% increase during light-off period on day 6 postinjection) were observed. Ventral tegmental area lesions (184 ng/mul of hypocretin2-sap, 0.25 microl, bilateral injections) did not produce significant changes in sleep, although most of the tyrosine hydroxylase- and neuronal nuclei-immunoreactive neurons in the ventral tegmental area were destroyed. Insomnia following hypocretin2-sap lesions of the substantia nigra could be secondary to increased motor activity resulting from reduction of tonic inhibitory control by the substantia nigra.

Animals↗

PubMed2005

Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects.

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response.

Acid-Base Equilibrium↗

PubMed2005

Water structure in aqueous solutions of alkali halide salts: FTIR spectroscopy of the OD stretching band.

Water structure making/breaking studies in solutions of five alkali halide salts (KF, KI, NaI, CsF and CsCl) in 4 wt% D(2)O in H(2)O mixtures have been performed by FTIR analysis of the OD stretching band in the full solubility range. The proposed method gives a microscopic picture of the water structure making/breaking character of the salts in terms of the hydrogen bonding between the water molecules in the solution. With the exception of CsCl, there is a very good correlation of the structure making/breaking character of the salts determined by FTIR analysis, and the viscosity coefficients of the solutions. The results fully support and explain previous studies of bubble attachment to microscopic salt particles of the above salts. The investigations support the primary importance of interfacial water structure in the explanation of the flotation of alkali halide salts in their brines.

Journal Article↗

PubMed2005

Gas exchange during exercise in habitually active asthmatic subjects.

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency.

Adolescent↗

PubMed2005

Concurrent HLA-related response factors mediate recombinant hepatitis B vaccine major adverse events.

Recombinant hepatitis B (HB) vaccines have successfully reduced infection, cirrhosis and carcinoma, but questions have endured about causality of serious adverse events following vaccination. After an event in a pediatric patient an investigation reviewed HLA vaccine response effects and analyzed genetics in reported cases. There are apparent common causal immune mechanisms among reported adverse events. HLA class II alleles/haplotypes linked to HB vaccine cellular/non-response and Crohn's disease can create conditions that actively/passively amplify, respectively, all or other components of the immune response to the HB vaccine. Presence of the HLA class I allele A2 can result in heavy cytotoxic T-cell activation and vaccine/self-peptide presentation to immune cells. If HLA autoimmune susceptibility alleles/haplotypes are present that control other immune response components, the probability is elevated that these will activate cross-reactive immune cells; the cells, their inflammatory secretions and/or auto-antibodies may initiate adverse events reflecting those susceptibilities. Probable DRB1 amplifying alleles are noted. High-resolution DNA typing and results analysis are described to test the hypothesis in known HB vaccine adverse event patients. Possible practical applications stemming from hypothesis validation are described.

Alleles↗

PubMed2005

A comparison of airborne ergosterol, glucan and Air-O-Cell data in relation to physical assessments of mold damage and some other parameters.

UNLABELLED: We report here a comparison of long duration air samples in 110 homes where the material collected on open faced filter cassettes was analyzed for beta 1,3-d glucan, ergosterol, cholesterol and endotoxin. These data were then compared to careful estimates of visible mold and Air-O-Cell data. All the values found except cholesterol were of a similar magnitude to values reported in the limited number of studies available. Glucan was measured with a factor G based assay of the Limulus Amebocyte Lysate followed by size exclusion chromatography. This showed that the majority of airborne glucan found in these houses was fungal in origin arising from both yeasts and intact spores, as well as hyphal and spore fragments. Hyphal and spore fragments together represented 16% of the intact spore counts but over a broad range. Correlations between airborne glucan were strong for ergosterol and visible mold. However, airborne ergosterol was more highly correlated to visible mold than glucan. Endotoxin and Air-O-Cell measurements were poorly or not related to the other measures in the study. This study provides confidence that long duration air samples of the toxin glucan and ergosterol are related to building damage. PRACTICAL IMPLICATIONS: Some studies of damp buildings have shown a relationship between extent of water/mold damage and symptoms. This study compared long duration air samples for glucan and ergosterol to extent of visible mold in houses measuring also the nature of the glucans present. Both measures were highly correlated to extent of visible mold damage in the houses; ergosterol was somewhat superior. Spore counts or prevalence of Asp/Pen in Air-O-Cell samples was not related to extent of visible mold damage but the observation of hyphal fragments was more likely when mold damage was present. This indicates that rigorous assessment of mold damage is a useful measure.

Air Pollution, Indoor↗

PubMed2005

Laser therapy for an obstructing primary tracheal lymphoma in a patient with AIDS.

A patient with AIDS presented with progressive dyspnea leading to respiratory failure with near complete airway obstruction due to primary tracheal lymphoma. Laser therapy was used locally to debulk the tumour, which facilitated extubation and led to definitive treatment with chemotherapy. Alternatives for local airway control are discussed.

Adult↗

PubMed2005

Differentiation of CD8 T cells in response to acute and chronic viral infections: implications for HIV vaccine development.

Successful HIV vaccine strategies will likely require the induction of robust cellular immune responses, in addition to strong humoral responses. Unfortunately, there is no clear molecular definition of an effective HIV-specific CD8 T cell response. In this review, we discuss the differentiation of CD8 T cells in response to acute and chronic viral infections. We then apply concepts derived from these studies to predict the desirable characteristics of HIV-specific CD8 T cell memory.

AIDS Vaccines↗

PubMed2004

A growth study of Coxiella burnetii Nine Mile Phase I and Phase II in fibroblasts.

Coxiella burnetii, a slow-growing, gram-negative, obligate intracellular bacterium, is the causative agent of Q fever in humans. The avirulent Phase II C. burnetii Nine Mile strain can invade and establish persistent infections in a wide variety of laboratory cell lines, and is generally considered to be easier to grow in culture than the wild-type Phase I organism. Efforts to improve Phase I organism yield in the BHK-21 cell line demonstrated that high CO2 conditions and the use of Dulbecco's modified Eagle's medium (DMEM) with 4.5 g/l glucose supplementation resulted in higher organism yields. Phase II organisms grown in the same cell line and conditions showed lower growth rates. Analysis revealed that increased average numbers of C. burnetii Phase I organisms within fibroblasts was due to higher growth rates within the hosts rather than to increased uptake or to increased cell-to-cell spreading. Addition of the nucleoside cytidine to the growth medium stimulated growth of Phase II but not Phase I organisms.

Animals↗

PubMed2004

Sodium dodecyl sulfate-poly(amidoamine) interactions studied by AFM imaging, conductivity, and Krafft temperature measurements.

The conductivity, kappa, and Krafft temperature, TK, of sodium dodecyl sulfate (SDS) with poly(amidoamine) dendrimers (PAMAM) of 0.0, 0.5, and 1.0 generations (G) have been determined at different surfactant as well as PAMAM concentrations. The critical micelle concentration of SDS increases with the increase in the amount of each generation and the additive effect of 0.5G is maximum. TK of SDS shows a systematic decrease with maximum reduction in the presence of 0.5G. Atomic force microscopy (AFM) captures a layered pattern of 1.0G in the form of nanorods and no AFM images are detected for 1.0G in the presence of SDS. All results demonstrate that SDS has favorable interactions with ester-terminated 0.5G PAMAM rather than amine-terminated 0.0G and 1.0G.

Journal Article↗

PubMed2004

Liquid/air interfacial structure of alcohol-octyl hydroxamic acid mixtures: a study by sum-frequency spectroscopy.

The molecular structure of the liquid/air interfaces of 1-octanol, 1-decanol, n-decane and the branched decyl alcohol EXXAL 10 has been studied by sum-frequency spectroscopy (SFS) in the C-H stretching vibrational region. The data suggest that the interfaces consist of ordered molecules with closely packed alkyl tails, in close to all-trans conformation with some gauche defects. The degree of surface ordering for the branched alcohol is much higher than for octanol and decanol. When octyl hydroxamic acid (OHA) is dissolved in 1-octanol it increases the gauche conformational defects in the interfacial chains, possibly due to mixing with the surface alcohol molecules and disrupting their ordering. In contrast, we suggest that when octyl hydroxamic acid is dissolved in EXXAL 10, the surface ordering of the alcohol chains does not change. We put forward the hypothesis that the appearance of new bands, belonging to the asymmetric methylene group vibrations and to the asymmetric methyl modes in the SF spectra of the mixture suggests that the surface OHA molecules are arranged with their hydrocarbon tails tilted very close to the interface.

1-Octanol↗

PubMed2003

Development of a urinary biomarker of human exposure to deoxynivalenol.

Deoxynivalenol (DON) is a mycotoxin frequently found as a contaminant of cereal crops and may be etiologically associated with adverse health effects in developing countries where considerable quantities of contaminated crops are consumed. We investigated the metabolism of DON in rats as a basis to establish methodology for a candidate biomarker of human exposure to this toxin and tested this methodology on urine samples from a potentially highly exposed population. Sprague-Dawley rats received a single dose of [14C]DON (5.0+/-0.1 mg/kg body weight, 5.5+/-0.1 microCi/kg) and the distribution of DON in body fluids was investigated over 72 h. DON and its metabolites were detectable in the plasma of rats with the highest levels at 8 h, at which time approximately 9% was bound to plasma protein. A total of 37% of the administered DON was excreted in the urine and DON-glucuronide was implicated as the major urinary metabolite based on reverse-phase HPLC analysis of beta-glucuronidase- and sulphatase-treated samples. An immunoaffinity column (IAC)-HPLC method was subsequently developed to measure urinary metabolites, with a view to establishing a urine-based human biomarker. Urine samples were collected from female inhabitants of Linxian County, China, a high risk region for oesophageal cancer (OC) and an area of potentially high DON exposure, and Gejiu, a low risk region in China. DON was detected in all 15 samples following beta-glucuronidase treatment and IAC enrichment with the identity of DON being confirmed by mass spectrometry. The mean levels of DON from the suspected high and low exposure regions of China were 37 ng/ml (range 14-94 ng/ml) and 12 ng/ml (range 4-18 ng/ml), respectively. This is estimated to correspond to daily exposures of 1.1-7.4 microg/kg/day and 0.3-1.4 microg/kg/day, respectively. This is the first reported measurement of a urinary biomarker for DON in both animals and humans and should facilitate epidemiological studies of disease associations with this mycotoxin.

Animals↗

PubMed2003

Effect of fibrin glue on air leak and length of hospital stay after pulmonary lobectomy.

AIM: Air leaks are a common cause of morbidity and prolonged hospital stay after pulmonary lobectomy. We reviewed our experience with intraoperative fibrin glue to determine if it reduced air leak and improved patient outcomes. METHODS: Records of patients undergoing pulmonary lobectomy for benign or malignant disease over a 4-year period (1998-2001) were reviewed. Data was collected on age, sex, pulmonary function, pulmonary pathology, use of fibrin glue, duration of chest tube drainage, length of hospital stay, and postoperative complications. RESULTS: Three hundred and sixty patients underwent lobectomy. Fibrin glue was used intraoperatively to seal air leaks in 102 of the 360 patients (study group: 102;control group: 258). Fibrin glue was used at the discretion of the surgeon, with some surgeons using it routinely. The groups did not differ in age (p=0.29), sex (p=0.42), FEV1 (p=0.57), or pathology (p=0.08). There were no differences in outcomes such as operative mortality (study: 2 of 102, control 6 of 258, p=0.85), empyema (study: 0 of 102, control: 3 of 258, p=0.55), prolonged (>7 days) air leaks (study: 10 of 20; control: 20 of 258, p=0.71), or length of hospital stay (study: 6.3+/-2.5 days, control:7.7+/-7.2 days, p=0.83). The use of fibrin glue was associated with a reduction in the duration of chest tube intubation (study: 4.1+/-3.2 days, control: 5.5+/-3.8 days, p=0.001). CONCLUSION: Patients treated intraoperatively with fibrin glue had a significantly shorter duration of chest tube intubation after pulmonary lobectomy than those treated conventionally. However, the use of fibrin glue did not significantly influence more clinically relevant outcomes such as length of hospital stay and incidence of prolonged (>7 days) air leaks.

Aged↗

PubMed2002

Persistence and reversibility of the elevation in free sphingoid bases induced by fumonisin inhibition of ceramide synthase.

These studies determined (1) the time course for sphingoid base elevation in the small intestines, liver, and kidney of mice following a single 25 mg/kg body weight (bw) oral dose (high dose) of fumonisin B(1) (FB(1)), (2) the minimum threshold dose of FB(1) that would prolong the elevated sphingoid base concentration in kidney following the single high dose, and (3) the importance of the balance between the rate of sphingoid base biosynthesis and degradation in the persistence of sphingoid base accumulation. Following the high dose of FB(1), there was an increase in sphinganine in intestinal cells and liver that peaked at 4 to 12 h and declined to near the control level by 48 h. In kidney, sphinganine peaked at 6-12 h but remained elevated until 72 h, approaching control levels at 96-120 h. Oral administration of 0.03 mg FB(1)/kg bw (low dose) for 5 days had no effect on the sphingoid bases in kidney. However, following an initial high dose, daily administration of the low dose prolonged the elevation in kidney sphinganine compared to mice receiving a single high dose. Thus, a single exposure to a high dose of FB(1) followed by daily exposure at low levels will prolong the elevation of sphinganine in kidney. In cultured renal cells FB(1) was rapidly eliminated, but elevated sphinganine was persistent. This persistence in renal cells was rapidly reversed in the presence of the serine palmitoyltransferase inhibitor (ISP-1), indicating that the persistence was due to differences in the rates of sphinganine biosynthesis and degradation. The in vivo persistence in kidney may be due to similar differences.

Acyltransferases↗

PubMed2001

Core-binding factor beta (CBFbeta), but not CBFbeta-smooth muscle myosin heavy chain, rescues definitive hematopoiesis in CBFbeta-deficient embryonic stem cells.

Core-binding factor beta (CBFbeta) is the non-DNA-binding subunit of the heterodimeric CBFs. Genes encoding CBFbeta (CBFB), and one of the DNA-binding CBFalpha subunits, Runx1 (also known as CBFalpha2, AML1, and PEBP2alphaB), are required for normal hematopoiesis and are also frequent targets of chromosomal translocations in acute leukemias in humans. Homozygous disruption of either the Runx1 or Cbfb gene in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system, and severely impairs fetal liver hematopoiesis. Results of this study show that Cbfb-deficient mouse embryonic stem (ES) cells can differentiate into primitive erythroid colonies in vitro, but are impaired in their ability to produce definitive erythroid and myeloid colonies, mimicking the in vivo defect. Definitive hematopoiesis is restored by ectopic expression of full-length Cbfb transgenes, as well as by a transgene encoding only the heterodimerization domain of CBFbeta. In contrast, the CBFbeta-smooth muscle myosin heavy chain (SMMHC) fusion protein generated by the inv(16) associated with acute myeloid leukemias (M4Eo) cannot rescue definitive hematopoiesis by Cbfb-deficient ES cells. Sequences responsible for the inability of CBFbeta-SMMHC to rescue definitive hematopoiesis reside in the SMMHC portion of the fusion protein. Results also show that the CBFbeta-SMMHC fusion protein transdominantly inhibits definitive hematopoiesis, but not to the same extent as homozygous loss of Runx1 or Cbfb. CBFbeta-SMMHC preferentially inhibits the differentiation of myeloid lineage cells, while increasing the number of blastlike cells in culture.

Animals↗

PubMed2001

Temporal changes in soil properties at an upland Scottish site between 1956 and 1997.

The aim of this study was to examine the frequency with which soil samples require to be taken in order to determine significant temporal changes in soil properties. The examination was carried out using data from Glensaugh Research Station in north-east Scotland where podzolic soils were sampled in 1956, 1977 and 1997, and by re-analysis of archived material. Significant differences in chemistry due to storage were detected, particularly decreases in pH of air-dried organic soils. In these cases original data were used for statistical analysis to establish changes between 1956 and 1997. Temporal changes were found for exchangeable Ca and Mg which generally decreased with time throughout the soil profile, whereas exchangeable H increased. Derived data, such as percent base saturation, declined dramatically due to decreases in exchangeable base cations. Similar podzolic soils were sampled at an adjacent Environmental Change Network (ECN) site in 1993. Application of statistical techniques to the ECN soil chemistry data allowed an estimation of the detectable change between any two years. These data along with the rates of temporal change from 1956 to 1997 allowed the calculation of the number of years required for measurable changes to be achieved. These changes and sampling intervals vary among different horizons and chemistries. Although they are site-specific, they do confirm that the current ECN protocols of a 5-year and 20-year sampling would be appropriate in order to detect changes in soil properties over time at this site.

Calcium↗

PubMed2001

Trends in stream water quality in Environmental Change Network upland catchments: the first 5 years.

Hydrochemical data from catchment streams at three Environmental Change Network (ECN) upland catchments in north-east Scotland, south-east Scotland and northern England have been subjected to statistical analysis to separate the components due to long-term trend, season and flow. The relative variances due to each are presented for pH, Ca, SO4-S, NO3-N, DOC and Cl. Long-term trends have been identified with increases in concentration for NO3-N and DOC, decreases in SO4-S concentrations, along with short-term seasonal fluctuations. Application of this trend technique has allowed the detection of changes and contributed to an improved understanding of catchment behaviour.

Environmental Monitoring↗