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Biomedical subjects

J A Graham

Publications and source records attributed to J A Graham.

At least 19 recordsLinked to original sources
PubMed2001

Episodes of pragmatic behaviors in parent-child interactions.

Pragmatic behavior, or the socially appropriate use of language, is important to parents of preschool children. In 1994 Becker noted several questions that still remain to be answered, including issues such as developmental changes in the pragmatic teaching of preschoolers and whether there are differences in the parents' goals for pragmatic teaching in private versus public interactions. The present study addressed these issues. 29 parent-child dyads were videotaped for 30 min. Transcripts were coded for episodes of pragmatic behavior that occurred in the dyadic interaction. Analysis indicated that pragmatic behaviors across the age groups largely focused on issues of what to say and how to say it. The teaching and use of pragmatic behaviors in public interactions is relatively important to parents of children between 2 1/2 and 4 years. The spontaneous use of pragmatic behaviors was the most common form of input (78% overall). Pragmatic behaviors were more often prompted with direct, as opposed to indirect, comments. Discussion focuses on a content analysis of the direct versus indirect prompts in the different age groups.

Child, Preschool↗
PubMed2000

Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation.

Damage-specific DNA binding (DDB) activity purifies from HeLa cells as a heterodimer (p127 and p48) and is absent from cells of a subset (Ddb(-)) of xeroderma pigmentosum Group E (XPE) patients. Each subunit was overexpressed in insect cells and purified. Both must be present for the damaged DNA band shift characteristic of the HeLa heterodimer. However, overexpressed p48 peptides containing the mutations found in three Ddb(-) XPE strains are inactive, and wild type p48 restores DDB activity to extracts from a fourth XPE Ddb(-) strain, GM01389, in which compound heterozygous mutations in DDB2 (p48) lead to a L350P change from one allele and a Asn-349 deletion from the other. Although these results indicate that these mutations are each responsible for the loss of DDB activity, they do not affect nuclear localization of p48. In normal fibroblasts, a 4-fold increase in p48 mRNA amount was observed 38 h after UV irradiation, preceding a similar elevation in p48 protein and DDB activity at 48 h, implying that p48 limits DDB activity in vivo. Because DNA repair is virtually complete before 48 h, a role for DDB other than DNA repair is suggested.

Amino Acid Substitution↗
PubMed2000

Nuclear transport of human DDB protein induced by ultraviolet light.

Human damage-specific DNA-binding (DDB) protein can be purified as a heterodimer (p48 and p127) that binds to DNA damaged by ultraviolet light. We report here the effects of UV irradiation on the cellular localization of each DDB subunit as a function of time using green fluorescent fusion proteins in three diploid fibroblast strains: repair-proficient IMR-90 and two repair-deficient xeroderma pigmentosum group E strains (XP95TO and XP3RO). Although p48 remained in the nucleus after UV irradiation, a dynamic nuclear accumulation of p127 from the cytoplasm was found after 24 h. In IMR-90 cells, the nuclear localization of p127 corresponded to the up-regulation of p48 mRNA and protein levels and of DDB activity. XP3RO cells showed delayed but similar kinetics with less transport, whereas XP95TO cells appeared to have different kinetics, suggesting that these cells exhibit different defects in p127 translocation. We propose that p48 might act as the transporter for nuclear entry of p127 but that a third factor might be necessary for efficient transportation.

Carbohydrates↗
PubMed2000

The nasal air sampler: a device for sampling inhaled aeroallergens.

OBJECTIVE: The object is to design, develop, and test a personal aerosol sampling device consisting of impaction samplers worn just inside the nostrils, driven by the wearer's respiration. The device provides a novel and unique measure of individual exposure to aeroallergens. It was conceived as an integral part of an allergen diagnostic system, in which collected aerosols are immunostained with monoclonal antibodies or the patient's IgE and associated particles positively identified using techniques of image analysis. METHODS: Each sampler comprises a slot impactor with a detachable impaction plate covered with either a specially developed medical adhesive or a protein-binding membrane. Sampler performance has been validated by rig tests of aerodynamic resistance and collection efficiency of different sized particles at various flow rates. There have also been field trials with human subjects which show that the sampler can be comfortably worn for periods of up to 4 hours. This is sufficient to gather a representative sample of inhaled allergens in most environments. RESULTS: The sampler collects an increasing proportion of particles in the inhalable range at and above 5 microm. This includes most bioaerosols of interest to allergists. Sampler prototypes have been built by CNC mill and stereolithography. Batches of samplers have been molded in biocompatible materials for field and clinical trials. CONCLUSIONS: The device successfully collects aeroallergens from a patient's own respiration. While developed specifically as a vehicle for the allergen diagnostic system, it can be adapted for studies of other aspects of air quality or for prophylactic use.

Administration, Inhalation↗
PubMed1998

The EPA health risk assessment of methylcyclopentadienyl manganese tricarbonyl (MMT).

This paper describes the U.S. Environmental Protection Agency's assessment of potential health risks associated with the possible widespread use of a manganese (Mn)-based fuel additive, methylcyclopentadienyl manganese tricarbonyl (MMT). This assessment was significant in several respects and may be instructive in identifying certain methodological issues of general relevance to risk assessment. A major feature of the inhalation health risk assessment was the derivation of Mn inhalation reference concentration (RfC) estimates using various statistical approaches, including benchmark dose and Bayesian analyses. The exposure assessment component used data from the Particle Total Exposure Assessment Methodology (PTEAM) study and other sources to estimate personal exposure levels of particulate Mn attributable to the permitted use of MMT in leaded gasoline in Riverside, CA, at the time of the PTEAM study; on this basis it was then possible to predict a distribution of possible future exposure levels associated with the use of MMT in all unleaded gasoline. Qualitative as well as quantitative aspects of the risk characterization are summarized, along with inherent uncertainties due to data limitations.

Administration, Inhalation↗
PubMed1997

Immunologic responses to vaccinia vaccines administered by different parenteral routes.

To develop a less reactogenic but equally immunogenic vaccine, this study of 91 human volunteers compared the safety and immunogenic potency of a new, cell culture-derived vaccinia virus vaccine administered intradermally and intramuscularly with the licensed vaccinia vaccine administered by scarification. Cutaneous pox lesions developed in a higher proportion of scarification vaccinees. Scarification and intradermal vaccine recipients who developed cutaneous pox lesions had more local reactions but also achieved significantly higher cell-mediated and neutralizing antibody responses than those who did not develop pox lesions. Although less reactogenic, intradermal or intramuscular administration of vaccinia vaccine without the concomitant development of a cutaneous pox lesion induced lower immune responses.

Antibodies, Viral↗
PubMed1997

Hypoxic vasoconstriction in pulmonary arterioles and venules.

Pulmonary microvessels (<70 microm) lack a complete muscular media. We tested the hypothesis that these thin-walled vessels do not participate in the hypoxic pressor response. Isolated canine lobes were pump perfused at precisely known microvascular pressures. A videomicroscope, coupled to a computerized image-enhancement system, permitted accurate diameter measurements of subpleural arterioles and venules, with each vessel serving as its own control. While vascular pressure was maintained constant throughout the protocol, hypoxia caused an average reduction of 25% of microvessel diameters. The constriction was reversed when nitric oxide was added to the hypoxic gas mixture. The nitric oxide reversal, combined with a lack of lobar blood flow redistribution as measured by fluorescent microspheres, shows that the constriction was active. This response suggests the unexpected potential for active intra-acinar ventilation-perfusion matching.

Animals↗
PubMed1996

The S-oxidative degradation of a novel corticosteroid tipredane (INN) Part III. Detailed investigations into the disulphoxidation of tipredane.

The methyl- and ethylsulphoxide diastereoisomers (V and VI) of the corticosteroid tipredane (INN, I) have been shown to undergo further stereoselective S-oxidation to yield diastereoisomeric disulphoxides (II). Interactive computer optimisation software was employed to develop semi-preparative chromatography conditions for the isolation of the disulphoxide diastereoisomers (II) and to develop a multiselective gradient HPLC analysis of tipredane (I), the four monosulphoxide diastereoisomeric pairs (V, VI, IX and X), the four disulphoxide diastereoisomers (II), the vinyl methyl and ethyl derivatives (XI and XII) and the methylsulphone of tipredane (VII). The four diastereoisomeric disulphoxides (II) have been isolated by semi-preparative HPLC and their structures unambiguously confirmed by high resolution multinuclear NMR and mass spectrometry. The stereochemical assignment of the four disulphoxide diastereoisomers (II), the ethylsulphoxide diastereoisomeric pair (VI), and the vinyl methyl and ethylsulphoxide diastereoisomeric pairs (IX and X) was determined by degradation/synthesis and relation to the S/R-disulphoxide (II) whose stereochemistry was determined by X-ray crystallography. The monosulphoxides (V and VI) showed a high degree of site and stereoselectivity towards further S-oxidation. S-Oxidation on the C-17 beta-substituent of tipredane occurred at a rate approximately 50-fold faster than that on the alpha-substituent. The disulphoxides (II) have been shown to be susceptible to thermolysis yielding the vinyl methylsulphoxide diastereoisomers (IX) preferentially. The loss of the ethylsulphenic acid from the disulphoxide diastereoisomers (II) could be rationalised in terms of the preferred rotamers of the C-17 substituents.

Administration, Topical↗
PubMed1995

Distribution of pulmonary capillary red blood cell transit times.

In theory, red blood cells can pass through the pulmonary capillaries too rapidly to be completely saturated with oxygen during exercise. This idea has not been directly tested because the transit times of the fastest red blood cells are unknown. We report the first measurements of the entire transit time distribution for red blood cells crossing single subpleural capillary networks of canine lung using in vivo fluorescence videomicroscopy and compare those times with the distribution of plasma transit times in the same capillary networks. On average, plasma took 1.4 times longer than red blood cells to pass through the capillary bed. Decreased transit times with increased cardiac output were mitigated by both capillary recruitment and a narrowing of the transit time distribution. This design feature of the pulmonary capillary bed kept the shortest times from falling below the theoretical minimum time for complete oxygenation.

Animals↗
PubMed1995

Sites of leukocyte sequestration in the pulmonary microcirculation.

The location and mechanisms of leukocyte sequestration in the pulmonary circulation have been investigated by using high-magnification in vivo videomicroscopy to record the passage of unlabeled native leukocytes through canine pulmonary capillaries. Of 650 leukocytes traversing capillary networks, 46 +/- 6% (SE) of the leukocytes passed through without stopping, 42 +/- 9% stopped in segments between junctions, and 12 +/- 4% stopped in junctions. Leukocytes rolling along arteriolar walls were nearly spherical, as 94% had aspect ratios (major axis divided by minor axis) < or = 1.25. To pass through the capillary bed, the leukocytes deformed into elongated shapes. Many leukocytes remained elongated after entering the venules (53% had aspect ratios > or = 1.25). Venular rolling was blocked by fucoidin (blocking both L- and P-selectin) but not by anti-P-selectin antibodies alone, indicating that rolling leukocytes adhered to the venular endothelium by L-selectin. These observations demonstrate that leukocytes deform to transit the capillary bed, that they stop more frequently in segments than in junctions, and that rolling leukocytes in the venular marginated pool adhere via L-selectin.

Animals↗
PubMed1995

Effect of capillary pressure and lung distension on capillary recruitment.

To investigate the effect of capillary pressure and alveolar distension on capillary recruitment, we used video-microscopy to quantify capillary recruitment in individual subpleural alveolar walls. Canine lobes were perfused with autologous blood either while inflated by positive airway pressure or while inflated by negative intrapleural pressure in the intact thorax with airway pressure remaining atmospheric. Low flow rates minimized the arteriovenous pressure gradient (< 5 mmHg), permitting capillary pressure estimation by averaging these pressures. Capillary pressure was varied stepwise from airway pressure to 30 mmHg above airway pressure. Capillary recruitment always began as capillary pressure exceeded airway pressure. At low positive airway pressures, the capillaries of the excised lobes opened suddenly over a narrow pressure range. AT higher airway pressures and in the intact thorax, recruitment occurred over a wide range of capillary pressures. We conclude that capillary perfusion begins when intracapillary pressure just exceeds alveolar pressure but that further increases in capillary pressure recruit capillaries depending on tension in the alveolar wall, whether imposed by positive airway pressure or by gravity when the lung is suspended in an intact thorax.

Air Pressure↗
PubMed1994

Cefuroxime axetil in the treatment of sinusitis. A review.

Cefuroxime axetil is a beta-lactamase-stable, second-generation, oral cephalosporin that penetrates sinus tissue in concentrations exceeding the MIC90 values (the minimum concentration of drug needed to inhibit the growth of 90% of an isolate of a particular microorganism) for pathogens most commonly associated with acute sinusitis, including Streptococcus pneumoniae and Haemophilus influenzae. A review of all clinical data published to date demonstrates that cefuroxime axetil has been evaluated in the treatment of acute sinusitis and acute exacerbations of chronic sinusitis ("acute-on-chronic sinusitis") in 18 clinical trials involving 1516 assessable patients. In 12 randomized, comparative trials, the rates of satisfactory clinical outcomes (cure or improvement, 79% to 100%) and bacteriologic eradication (84% to 100%) reported with the use of 250 mg of cefuroxime axetil twice daily were similar to those observed with the use of amoxicillin, amoxicillin/clavulanate potassium, cefaclor, cefadroxil, cefixime, clarithromycin, and doxycycline. In these comparisons, no antibiotic demonstrated any therapeutic advantages over cefuroxime axetil regarding time to symptom abatement. Cefuroxime axetil was at least as well tolerated as the other antibiotics. Overall, the role of cefuroxime axetil in the treatment of sinusitis appears to be as one of the broad-spectrum antibiotics that can be used for infections due to the most commonly implicated sinus pathogens, especially those due to the increasing number of relatively penicillin-resistant strains of S pneumoniae and beta-lactamase-producing strains of H influenzae and Moraxella catarrhalis.

Acute Disease↗
PubMed1994

Pyoderma gangrenosum in infants and children.

Pyoderma gangrenosum is an uncommon ulcerative skin disorder that occurs in all age groups. Approximately 4% of patients are infants and children. There are several notable differences between the childhood and adult manifestations of the disease, including the distribution of lesions and associated disorders. We reviewed the childhood cases (< or = 18 yrs of age) of unequivocal pyoderma gangrenosum in the English literature and tabulated the trends in clinical features, associated disorders, and therapy. We report our 3-week-old patient, the youngest documented case. Of the 46 patients, only 4 were less than 1 year of age. A systemic illness was present in 74% of the older children, most commonly, ulcerative colitis. Only one infant had an associated problem (HIV+) at the time of onset. Infants appear to have an unusual distribution of perianal and genital lesions not often described in other age groups. Our review suggests that pyoderma gangrenosum in children has a similar clinical appearance to that in adults. It is associated with some of the same underlying disorders, but with different frequencies. The distribution of lesions in children is similar, often involving the lower extremities, but pyoderma gangrenosum of the head and face appears to be more common in children. Infants may have ulcers in genital and perianal areas. The most frequently prescribed treatment for children is systemic corticosteroids, which generally are very effective.

Adolescent↗
PubMed1994

Effect of increasing flow on distribution of pulmonary capillary transit times.

The complex morphology of the pulmonary capillary network causes capillary transit times to be dispersed about a mean. It is known that flow-induced decreases in mean capillary transit time are partially offset by capillary recruitment and distension, but the effect of these factors on the rest of the distribution of transit times is unknown. We have studied the relationship between blood flow, capillary recruitment, and the distribution of transit times in isolated canine lungs with videomicroscopy. Doubling baseline lobar blood flow recruited capillaries. All transit times in the distribution decreased, as did relative dispersion. Doubling flow again caused a further decrease in transit times, but neither capillary recruitment nor relative dispersion changed significantly. We conclude that capillary transit times become more homogeneous as lobar flow increases from low to intermediate levels. Further increases in flow across a fully recruited network are associated with decreases in transit times but not with more homogeneous capillary perfusion.

Animals↗
PubMed1994

Stability of alveolar capillary opening pressures.

Little is known about the stability of the process by which pulmonary capillaries open. To investigate this process, pulmonary capillary perfusion patterns in isolated pump-perfused canine lobes were studied using video microscopy. After pump flow was set to perfuse one-half of the capillaries, the pump was turned off and all of the capillaries emptied. Turning the pump back on reopened the capillaries. The on-off cycle was repeated six times. If the same capillaries were perfused during each observation, it would demonstrate that there were stable and significant differences between individual capillary opening pressures, causing consistent recruitment of those capillaries with the lowest opening pressures. Alternatively, variable perfusion patterns would result if capillary opening pressures changed between observations, if the differences in opening pressures between capillary segments were negligible, or if experimental conditions changed between cycles. The perfusion pattern was more reproducible than expected by chance alone, which indicated the existence of stable differences among alveolar capillary opening pressures.

Animals↗