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Biomedical subjects

L J Smith

Publications and source records attributed to L J Smith.

At least 199 records · Page 11Linked to original sources
PubMed1986

Late and immediate systemic-allergic reactions to inhalant allergen immunotherapy.

Systemic-allergic reactions to allergen immunotherapy were prospectively studied in four allergy treatment centers to assess frequency and specific attributes of these episodes relative to several variables. A total of 20,588 extract injections were administered to 628 patients. Forty-two patients experienced a systemic reaction (7%). Fifty-two systemic reactions occurred in total. Eight patients accounted for 18 of the reactions. Late systemic reactions, occurring from 35 minutes to 6 hours after injection, accounted for 38% of all reactions. Extracts containing only pollen antigens were more commonly associated with immediate and late systemic reactions relative to other extracts (p less than 0.001 and p less than 0.01, respectively). There were no significant reaction-rate differences whether immunotherapy was at maintenance or increasing doses or if the time of injection was during a pollinating or nonpollinating season. The most common clinical manifestations of the systemic reactions were generalized pruritus and urticaria. We conclude that patients receiving extracts containing only pollen antigens have increased systemic-allergic reaction rates. A subgroup of patients are at risk for recurrent reactions. Finally, late systemic reactions to immunotherapy are not rare events and pose a definite risk to the individual patient.

Allergens↗
PubMed1986

Adherent cells in cultures of blast progenitors in acute myeloblastic leukemia.

Blast cells from patients with acute myelogenous leukemia (AML) grow exponentially in suspension culture and form colonies in cultures "stiffened" with methylcellulose; under both culture conditions, cells are generated which have the ability to adhere to plastic or glass. These adherent cells lack the capacity to form colonies, to proliferate in liquid culture or to support growth. Adherent cells are generated in parallel with changes in the frequency of clonogenic cells and express surface markers of AML blasts but with a higher frequency of an antigen recognized by the monoclonal MO1, a late stage marker associated with the macrophage differentiation lineage. While the appearance of adherent cells provides further evidence that blast cells follow differentiation programs in culture, the generation of adherent cells does not indicate that normal differentiation is occurring; rather the data is consistent with the view that components of normal monocytic differentiation programs are assembled abnormally in the programs of some blast progenitors.

Cell Adhesion↗
PubMed1986

The early involvement of pulmonary prostaglandins in hyperoxic lung injury.

To further study the role of arachidonic acid metabolites in the development of hyperoxic lung injury and the function of PMNs and/or alveolar macrophages in facilitating this role, we exposed adult rabbits to greater than 95% O2 or air for 24, 40, 48, or 65 hours. At the end of each study, bronchoalveolar lavage [BAL] of the left lung was performed, and the right lung was inflated and fixed for light and electron microscopy. PGE2, 6-keto-PGF1 alpha and thromboxane B2 were measured by RIA in arterial and venous plasma at the beginning and end of each study and in BAL fluid obtained at sacrifice. Production of these three PGs by BAL cells placed in cell culture was also measured. Significant hyperoxic lung injury did not develop until 65 hours, as evidenced by significant increase in BAL total protein and percent PMNs, and by morphologic findings. At 40 hours, however, BAL fluid PGE2 and 6-keto-PGF1 alpha increased and BAL cell production of all 3 PGs was significantly increased (p less than .05). In summary, the early PG increases observed in these studies may directly contribute to the development of hyperoxic lung injury or, rather, may be representative of a generalized increase in all arachidonic acid metabolites, including the lipoxygenase pathway. The increase in BAL cell PG production and increased PG concentrations in BAL fluid prior to any increase in BAL PMNs suggest that the AM may be the source of the early arachidonic acid metabolite increase in response to hyperoxia.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The effects of hyperoxia on pulmonary clearance of Pseudomonas aeruginosa.

Among the toxic effects of hyperoxia may be impaired pulmonary clearance of gram-negative bacteria. To better define this effect, we exposed BALB/c mice to 100% O2 for 24, 48, or 72 hr and intrabronchially inoculated them with 10(6) Pseudomonas aeruginosa. Clearance was assessed 4 hr later by quantitative lung cultures of air- and O2-exposed mice. Clearance was first reduced at 48 and 72 hr in mice exposed to O2. To determine the mechanism responsible, we measured bronchoalveolar lavage neutrophil (PMN) counts and neutrophil chemotactic activity at 0, 2, and 4 hr after instillation of P. aeruginosa into mice first exposed to air or O2 for 48 hr. Air-exposed mice had more PMNs than did O2-exposed mice after challenge (13.3 +/- 2.1 X 10(5) vs. 4.4 +/- 0.6 X 10(5)). There was no difference in neutrophil chemotactic activity between air- and O2-exposed mice at any time, although chemotactic activity increased in both groups after challenge. Our data suggest that hyperoxia impairs pulmonary clearance of P. aeruginosa by decreasing the influx of PMNs and that this effect is not due to diminished chemotactic activity in bronchoalveolar lavage fluid.

Animals↗
PubMed1986

Neonatal fat digestion and lingual lipase.

Lingual lipase (LL) activity, pH, and products of fat hydrolysis were determined in gastric aspirates from preterm infants who received formula milk feeds by a nasogastric tube. In 1-hourly (n = 9), 2-hourly (n = 8) and 3-hourly (n = 9) fed infants LL activity increased to reach its maximum value at 60, 90, and 120 min respectively after the feeds, and gastric pH levels fell from about 6.0 to less than 3.5. There was a reduction in triglyceride content to 50% of the initial value, measured immediately after a feed, and the products of hydrolysis were mainly diglycerides and FFA. In a subsequent study 3-hourly fed infants (n = 8) had a tube feed followed by a bottle feed, and then a bottle feed followed by a tube feed on successive days (cross-over). The LL activity observed after a bottle feed (mean maximal value 23.8 mumol FFA/ml/h) was significantly higher than after a tube feed (19.1 mumol FFA/ml/h). It is suggested that substantial triglyceride hydrolysis takes place in the stomach due to lingual lipase, and sucking seems to enhance enzyme production.

Dietary Fats↗
PubMed1986

Characterization of the airway response to inhaled leukotriene D4 in normal subjects.

To better understand the role of leukotriene D4 (LTD4) in the pathogenesis of airway hyperreactivity, we administered aerosolized LTD4 on multiple occasions to 6 normal subjects and measured specific airway conductance (SGaw) by body plethysmography and the flow rate at 30% of vital capacity from partial forced expiratory maneuvers (V30P). Dose-response curves generated from standard bronchoprovocation tests revealed that LTD4 was 280 to 590 times more potent as a bronchoconstrictor than was methacholine. The airway response to single bronchoconstricting doses of LTD4 administered on separate days was reproducible for SGaw (r = 0.86, p less than 0.05) and V30P (r = 0.95, p less than 0.005). The response to 3 consecutive single-dose LTD4 challenges performed on the same day, allowing SGaw and V30P to return to greater than 90% of the control value between challenges, demonstrated tachyphylaxis: the response to the third dose was significantly less than the response to the first dose for SGaw (p less than 0.001) and for V30P (p less than 0.01). A single bronchoconstricting dose of LTD4, given before a standard methacholine dose-response challenge, lowered the concentration of methacholine needed to decrease V30P 30% (p less than 0.05) and SGaw 35% (p = 0.09). A single bronchoconstricting dose of methacholine preceding a standard methacholine challenge did not have this effect. LTD4 and methacholine demonstrated a cumulative dose-effect when progressively higher concentrations were inhaled. In summary, the airway response to LTD4 is reproducible, exhibits tachyphylaxis, and a cumulative dose-effect occurs. As well, LTD4 increases the responsiveness of normal airways to methacholine.

Adult↗
PubMed1986

Hyperoxic lung injury in mice: a possible protective role for prostacyclin.

Arachidonic acid metabolites have biologic properties that can mimic the pulmonary changes produced by hyperoxic exposure, but little information is available regarding their importance in this setting. The role of prostacyclin (PGI2) and thromboxane (Tx) A2 in oxygen-induced lung injury was evaluated by exposing mice to 100% oxygen for up to 4 days and measuring plasma and bronchoalveolar lavage (BAL) fluid concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of PGI2, and TxB2, a metabolite of TxA2. To determine whether a relationship exists between changes in these arachidonic acid metabolites and the severity of the lung injury, we also measured mortality, BAL protein concentration, BAL angiotensin-converting enzyme (ACE) activity, and plasma lactate dehydrogenase activity, and we examined lung sections by light and electron microscopy. After 3 days of exposure to 100% oxygen, microscopic and biochemical changes consistent with mild lung damage were found, but there was no increase in either plasma or BAL 6-keto-PGF1 alpha concentration. On day 4, severe lung damage was present. and BAL 6-keto-PGF 1 alpha level increased threefold (P less than 0.001). The level of TxB2 in BAL fluid did not change on any day. Twice-daily administration of either a high (5 mg/kg) or a low (1 mg/kg) dose of indomethacin reduced BAL concentrations of 6-keto-PGF1 alpha, and it resulted in increased mortality and higher BAL protein concentration and BAL ACE activity. These data suggest that TxA2 has little if any role in the pathogenesis of oxygen-induced lung injury, whereas prostacyclin may play a protective role.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Comparison of cutaneous and bronchial reactivity to leukotriene D4 in humans.

To establish whether a relationship exists between cutaneous and bronchial reactivity to leukotriene D4 (LTD4), endpoint cutaneous reactivity and bronchial reactivity were determined in six patients with asthma, six patients with seasonal allergic rhinitis, and six nonatopic men. In all subjects, increasing doses of LTD4 produced decreases in specific airway conductance (SGaw) and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (V30P). Intracutaneous injections of LTD4 and histamine resulted in immediate wheal and erythema reactions in all patients. Serial 10-fold dilutions of LTD4 and histamine were injected to establish the lowest dose capable of producing a 4 mm wheal with erythema. Endpoint cutaneous reactivity to LTD4 ranged from 1 mumol to 100 pmol in controls and from 100 nmol to 1 fmol in patients with asthma, but statistically significant differences between groups were not apparent even with inclusion of six additional subjects. No meaningful correlations were found between the quantity of LTD4 producing the threshold cutaneous reaction and the dose of inhaled LTD4 that produced a 35% decrease in SGaw and 30% decrease in V30P. In contrast to the bronchi, where subjects in all three groups were 264 to 840 times more sensitive to LTD4 than to methacholine, 11/18 subjects (3/6 with asthma) were less sensitive to LTD4 than to histamine in terms of endpoint cutaneous reactivity. However, seven of 18 subjects who were more sensitive to LTD4 than to histamine had relative potencies ranging from 5 to 500,000.

Asthma↗
PubMed1986

Comprehensive immunization delivery in conjunction with influenza vaccination.

All patients and employees presenting for influenza A and B vaccination were studied for the need for other immunizations or tests, based on criteria of the Immunization Practices Advisory Committee. More than 72% of patients and employees needed at least one other vaccine or test. During a 4 1/2-month period, 1,353 doses of influenza virus vaccine, bivalent, types A and B, were prescribed. Health care providers ordered doses of diphtheria and tetanus toxoids (adult) for 36.8% of these recipients, pneumococcal vaccine, polyvalent 23, for 42.1%, and a tuberculin skin test for 36.3%. Determinations of hepatitis B titers or hepatitis B vaccine doses were ordered for 140 individuals. Patients older than 60 years needed additional immunizations with greater frequency. Rates of delayed adverse reactions (35.9%) and subsequent self-medication (11.7%) were recorded. The systemic adverse reaction rate was 17.3%. Annual influenza vaccination programs are valuable public health opportunities to determine immunizations needed by patients who might not otherwise receive a comprehensive, individualized review of the status of their immunization protection.

Adolescent↗
PubMed1985

Normal ranges of hip motion of infants between nine and 24 months of age.

The means and standard deviations were obtained for hip extension limitation, internal rotation, external rotation and abduction at nine, 12, 18 and 24 months of age from a sample of 86 normal, healthy children. Statistically significant changes were found for three of the four motions tested. Hip extension limitation decreased from 10 degrees at nine months to 3 degrees at 24 months. At nine months external rotation was greater than internal rotation in all cases, but with increasing age the mean values for the two motions began to approximate each other. There was a statistically significant positive correlation between infants with the greatest hip extension limitation and the degree of external rotation. There was also a significant negative correlation between the least hip extension limitation and greater abduction.

Child Development↗
PubMed1985

The effect of inhaled leukotriene D4 in humans.

Leukotriene D, (LTD4) is a potent bronchoconstrictor that may play an important role in asthma. To better characterize the effect of LTD4 on human airways, normal, rhinitic, and asthmatic subjects underwent inhalation challenge tests with LTD4 and methacholine. In all subjects increasing concentrations of LTD4 produced a parallel decrease in specific airway conductance and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (V30P). These changes occurred independent of any decrease in FEV1 or increase in functional residual capacity. The airway response to LTD4 was maximal within 2 to 3 min, persisted for approximately 30 min, and resolved over 1 to 3 h. Late effects were not seen. Rhinitic subjects were 3 to 5 times (p less than 0.01) and asthmatic subjects were 25 to 100 times (p less than 0.001) more sensitive than were normal subjects to LTD4. All 3 groups of subjects were 250 to 850 times more sensitive to LTD4 than to methacholine. Significant correlations were found between the concentration of LTD4 and the concentration of methacholine that produced a 35% decrease in specific airway conductance (r = 0.874; p less than 0.006) and a 30% decrease in V30P (r = 0.751; p less than 0.04). These results confirm that LTD4 is a potent bronchoconstrictor in humans, with a rapid onset of action and a prolonged effect. In contrast to previous reports, we found that LTD4 has an equal effect on both large and small airways and that both asthmatic and normal subjects have the same degree of increased sensitivity to LTD4 as to methacholine.

Adult↗
PubMed1985

Changes in dentin appositional rates during pregnancy and lactation in rats.

Dentin appositional rates were determined in pregnant and lactating rats and compared with those in non-pregnant, age-matched controls. Appositional rates were calculated from measurements of distance between fluorescent mineralized tissue markers. There were significant increases in dentin apposition during pregnancy, with the greatest increases seen in the first two weeks. Dentin appositional rates decreased significantly during mid-lactation. These results indicate that homeostatic changes during pregnancy and lactation affect mineralized tissue accretion.

Animals↗
PubMed1985

Evaluation of the risks of anticoagulation therapy following experimental craniotomy in the rat.

The risk of hemorrhagic complications with anticoagulation therapy in patients following intracranial surgery has prevented investigation of the potential use of heparin in the early postoperative period. The authors have evaluated the safety of anticoagulation therapy following experimental craniotomy in male Holtzman rats. The dose and schedule of heparin administration, which elevated and maintained the activated partial thromboplastin time (APTT) within the therapeutic range of 1 1/2 to 3 X control APTT, was alternating doses of 400 and 500 IU/kg injected subcutaneously every 6 hours. This schedule was initiated 2, 4, 7, 10, and 14 days after craniotomy and was continued for 72 hours thereafter. The results demonstrated that the incidence of intracerebral hemorrhage declined as the postoperative interval prior to initiation of anticoagulation increased. If anticoagulation therapy was initiated during the first 7 postoperative days, the risk of intracerebral hemorrhage was high (mean 14.7%): however, if an additional 3 to 7 days elapsed prior to initiation of anticoagulation, the incidence of intracerebral hemorrhage dropped significantly (mean 0%) (p less than 0.05). These results suggest that anticoagulation therapy can be safely initiated 10 to 14 days after craniotomy.

Animals↗
PubMed1985

Hyperoxic lung injury: biochemical, cellular, and morphologic characterization in the mouse.

Controversy exists over the mechanism by which oxygen produces lung damage. This study was designed to characterize the biochemical, cellular, and morphologic responses of mice exposed to 100% oxygen and thereby provide the basis for investigating the mechanisms producing the lung damage as well as for evaluating treatment strategies. After 1 day of exposure, plasma lactate dehydrogenase (LDH) activity and LDH isoenzyme 1, 2, and 3 concentration increased, whereas the level of isoenzyme 1 recovered from the lung, heart, and kidney decreased. On day 2, the level of these plasma isoenzymes increased further, whereas isoenzyme 1 concentration remained decreased only in the lung. In addition, the number of cells obtained by bronchoalveolar lavage (BAL) doubled, and electron microscopy revealed type 1 cell and endothelial cell damage. On day 3, the amount of BAL protein doubled, BAL angiotensin-converting enzyme (ACE) activity increased sevenfold, plasma ACE activity decreased 39%, and electron microscopy revealed extensive cell damage. On day 4, the injury was much worse and was associated with a 10-fold increase in the number of BAL cells, nearly all of which were polymorphonuclear leukocytes (PMNs). On day 5, greater than 65% of the mice were dead. The data suggest that in mice (1) an increase in plasma LDH activity and a shift in its isoenzyme pattern are sensitive markers of hyperoxic lung damage, (2) the initial injury produced by oxygen is independent of PMNs, and (3) the damage to alveolar epithelial cells and endothelial cells is severe and occurs at the same time. Studies using this well-characterized model can now be designed to further define the mechanisms that initiate hyperoxic lung damage and that contribute to its progression.

Animals↗
PubMed1985

Production of heterologous antibodies specific for murine B-cell leukemia (BCL1) immunoglobulin by immunization with synthetic peptides homologous to heavy chain hypervariable regions.

Three peptides homologous to each heavy chain hypervariable region expressed by murine B-cell leukemia, BCL1, were synthesized in vitro by solid phase peptide synthesis. All three synthetic peptides elicited responses in rabbits which were immunized with synthetic peptide or synthetic peptide conjugated to the carrier keyhole limpet hemocyanin. Six individual rabbits were immunized, five of which responded by producing antisera which react specifically in radioimmunoassay with the synthetic peptide used as immunogen. One antiserum has specificity for the peptide homologous to the first hypervariable region, three antisera have specificity for the peptide homologous to the second hypervariable region, and one has specificity for the peptide homologous to the third hypervariable region. The five antisera with high titers of antibody recognizing synthetic peptide also specifically recognize native immunoglobulin M secreted by BCL1 tumor cells as demonstrated by immunoprecipitation followed by sodium dodecyl sulfate: polyacrylamide gel electrophoresis and autoradiography. These five antisera do not show reactivity with immunoglobulin secreted by spleen cells from normal BALB/cAn mice or by B-cells from unrelated tumors and cell lines. However, as determined by absorption experiments, the majority of antibodies in each antiserum are directed against the respective synthetic peptide, and only a small portion are reactive with native immunoglobulin M. Nonetheless, these results indicate use of synthetic peptides as a potential alternative source of immunogen for production of antitumor antibody.

Amino Acid Sequence↗
PubMed1985

Long term treatment with clonidine during the development of hypertension in spontaneously hypertensive rats.

Chronic administration of clonidine in the drinking water of spontaneously hypertensive (SH) rats from 11 through 17 weeks of age prevented the further development of hypertension in this model. A dosage adjustment (from about 0.1 to 0.5 mg/kg) was required to maintain a stable systolic pressure of about 200 mmHg. After six weeks of treatment clonidine was withheld for 48 hrs during which time blood pressure increased to a level similar to that of untreated controls.

Animals↗