Biomedical subjects

J Goff

Publications and source records attributed to J Goff.

At least 19 recordsLinked to original sources

PubMed2002

Dose ranging pharmacokinetic trial of high-dose alicaforsen (intercellular adhesion molecule-1 antisense oligodeoxynucleotide) (ISIS 2302) in active Crohn's disease.

BACKGROUND AND AIMS: To evaluate the safety, pharmacokinetics and clinical efficacy of the intercellular adhesion molecule-1 antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) at 250-350 mg in Crohn's disease. METHODS: : Patients (> 50 kg) with active Crohn's disease (Crohn's disease activity index > or = 220) were assigned by gender, randomly, to two alicaforsen treatment groups: 300 or 350 mg, infused intravenously three times a week for 4 weeks. All patients weighing 36-50 kg received 250 mg of alicaforsen. Background aminosalicylates, antibiotics, immunosuppressives and corticosteroids were permitted, but tumour necrosis factor-alphainhibitors were prohibited. The primary end-point was clinical remission (Crohn's disease activity index < or = 150). RESULTS: Twenty-two patients were enrolled with a mean baseline Crohn's disease activity index of 304. Steroids were used by 27%, 5-aminosalicylic acid by 68% and immunosuppressives by 27%; 23% had previously received infliximab. Five subjects withdrew after one to three infusions for infusion-related symptoms. Nine patients (41%) experienced clinical remission. Fifty-three per cent of the evaluable subjects receiving more than three infusions experienced remission (18% at week 8; 29% at week 12). The overall response, using a minimum decrease of 70 in the Crohn's disease activity index, was 41-47% for the evaluable group, at weeks 8 and 12. The median duration of remission was 14 weeks. Plasma pharmacokinetic results showed overlapping levels (Cmax, AUC) for the three doses. The infusion-related reaction profile consisted of fever, chills, headache, nausea, emesis or arthralgias, typically occurring 2-4 h after completion of the first infusion. Reactions were less frequent in patients receiving background corticosteroids. The 2-4-h transient post-infusion partial thromboplastin time prolongation values, a class effect of phosphorothioate oligonucleotides, were 18, 21 and 23 s for 250, 300 and 350 mg, respectively. CONCLUSIONS: Alicaforsen (ISIS 2302), at fixed doses of 300 and 350 mg, achieved the desired drug exposure and may be an effective therapy for Crohn's disease. Infusion-related reactions were observed less frequently in patients on corticosteroids, and with decreasing frequency with continued treatment.

Adolescent↗

PubMed2002

Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease.

BACKGROUND AND AIMS: To evaluate the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) in Crohn's disease. METHODS: Active (Crohn's disease activity index (CDAI) 200-350), steroid dependent (prednisone 10-40 mg) Crohn's patients were randomised into three treatment groups: placebo versus ISIS 2302 (2 mg/kg intravenously three times a week) for two or four weeks. Patients were treated in months 1 and 3, with steroid withdrawal attempted by week 10. The primary end point (steroid free remission) was a CDAI <150 off steroids at the end of week 14. RESULTS: A total of 299 patients were enrolled, with a mean baseline CDAI of 276 and steroid dose of 23 mg/day. Rates of steroid free remission were equivalent for the two and four week ISIS 2302 groups (20.2% and 21.2%) and the placebo group (18.8%). At week 14, steroid withdrawal was successful in more ISIS 2302 patients compared with placebo treated patients (78% v 64%; p=0.032). Steroid free remission was highly correlated with exposure (p=0.0064). Other clinical responses were correlated with exposure, with significant results versus placebo being observed in the highest area under the curve subgroup. CDAI scores decreased by 136 (112) at week 14 versus 52 (107) for placebo (p=0.027) and inflammatory bowel disease score questionnaire improved by 43 (31) versus 15 (36) for placebo (p=0.027). CONCLUSIONS: Although the primary outcomes failed to demonstrate efficacy, pharmacodynamic modelling suggests that alicaforsen (ISIS 2302) may be an effective therapy for steroid dependent Crohn's disease.

Adolescent↗

PubMed2002

Metabolic responses of transition Holstein cows fed anionic salts and supplemented at calving with calcium and energy.

The objective of this study was to determine the concentrations of plasma Ca, P, Mg, nonesterified fatty acids (NEFA), 3-hydroxybutyrate (BHBA), and glucose in transition cows fed anionic salts prepartum and provided with calcium and energy supplements at calving. The study was conducted on a Florida Holstein dairy farm from November to December 1997. Treatments consisted of no treatment (n = 30); 60 g of Ca as calcium chloride, orally (n = 30); 110 g of Ca as calcium propionate 510 g plus 400 g of propylene glycol, orally (n = 30); two doses of 60 g of Ca as calcium chloride, one at calving and the second 24 h later, orally (n = 30); and 10 g of Ca as borogluconate, intravenously (n = 30). Treatments were administered within 12 h after parturition. Blood samples were collected at d 1 (parturition), 2, 3, 6, 9, and 12 after calving. Plasma total Ca, P, Mg, NEFA, BHBA, and glucose were measured. There were no differences in the concentrations of the blood metabolites among treatments.

3-Hydroxybutyric Acid↗

PubMed2001

The prevalence of occult carotid artery stenosis in patients with head and neck squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Risk factors for atherosclerotic carotid artery disease (ASCAD) and squamous cell carcinoma of the head and neck region (HNSCCA) are similar. This study was conducted to determine whether patients with HNSCCA have an increased rate of occult ASCAD compared with the general population. STUDY DESIGN: A cross-sectional study was performed to identify the prevalence of clinically significant ASCAD in the specific population of patients with a diagnosis of HNSCCA using noninvasive color flow duplex imaging. In addition, the demographic variables and risk factors for head and neck cancer and for carotid disease, as identified in the literature, were recorded with the use of a questionnaire. METHODS: Forty-nine patients with a diagnosis of HNSCCA completed the questionnaire and then had a duplex screening examination. RESULTS: The most common risk factor identified was tobacco smoking in 41 of 49 patients (84%). ASCAD was identified in one patient (2%). The stenosis in that patient was less than 60%. CONCLUSIONS: We conclude from this study that even though patients with HNSCCA usually have risk factor(s) associated with ASCAD, the rate of occult ASCAD was not different from that found in the general population. Thus, routine screening of patients with HNSCCA with color flow duplex imaging to detect occult ASCAD is not warranted.

Adult↗

PubMed2001

Accuracy and modifying factors of the sonographic estimation of fetal weight in a high-risk population.

There have been a number of reviews assessing the accuracy of different methods of sonographic estimation of fetal weight, without identifying any clearly superior equation. In order to optimise accuracy in a high-risk population, we decided to compare some of the most popular early equations with the newer volume-based equations, and to try and identify factors that affect the ability of these equations to estimate fetal weight accurately We collected the scan and delivery details of 192 fetuses born within one week of a sonographic estimation of fetal weight. We then applied three of the most popular equations and two newer volume-based equations to the recorded fetal biometric parameters to assess the performance of each equation overall, and under varying maternal, fetal, and scan conditions. The equations of Shepard, Hadlock A, Hadlock B and Combs produced similar results with systematic (mean) errors in the range 1.2-1.9% and random error characterised by one standard deviation in the range of 8.6-9.5%. Dudley's volume-based equation produced a significant systematic error in the form of a mean error of 7.4%, which corresponds to a mean birthweight (BW) which is 7.4% above the mean estimated fetal weight (EFW). When we stratified the study group by birthweight, Combs' equation produced significant differences in the mean error, (p < 0.00001), that ranged from a mean overestimation in fetal weight of 8.5% for babies with BW < 1000 g to a mean underestimation in fetal weight of 6.2% for babies with BW > 3000 g. Oligohydramnios resulted in a trend towards an increased mean error for all equations which was only statistically significant for Hadlock B. The equations Shepard and Hadlock A performed best in our high-risk population. They produced the smallest systematic errors across the entire study group and were not adversely affected by variations in birthweight, liquor volume, or fetal presentation. The newer, volume-based equations were disappointing, producing large systematic errors. Large random errors in all equations continue to be the Achilles' heel that limit the value of sonographic EFW.

Biometry↗

PubMed2000

Malignant carotid body tumor: a case report.

Carotid body tumors (CBTs) have an unpredictable history with no correlation between histology and clinical behavior. Of reported cases since 1891, local and distant metastases appear in approximately 10% of cases and remain the hallmark of malignancy. Currently, there are not enough data to support a single treatment regimen for malignant CBTs. The reported case demonstrates some unanswered issues with regard to malignant CBTs to include lymph node dissection, the need for carotid resection, and the role of radiation therapy. A 46-year-old pathologist underwent a resection of a Shamblin I CBT, to include jugular lymph node sampling, without complication. There was lymph node involvement, and tumor cells were found on the margins of the pathologic specimen. Subsequent carotid resection with reversed interposition saphenous vein graft and modified neck dissection were performed again without complication. Follow-up at 4 years has been uneventful. Diagnosis of CBTs with the use of magnetic resonance angiography, magnetic resonance imaging, color flow duplex scanning, and the role of arteriography are reviewed. The current treatment options are discussed with reference to primary lymph node sampling, carotid resection, and neck dissection in malignant cases. This case demonstrates that the unpredictable nature of CBTs and their malignant potential warrant aggressive initial local treatment to include jugular lymph node sampling and complete tumor resection.

Carotid Body Tumor↗

PubMed1998

Aluminum and acid effects on calcium and phosphorus metabolism in young growing chickens (Gallus gallus domesticus) and mallard ducks (Anas platyrhynchos).

Acidification is associated with increased mortality, reduced growth, and bone abnormalities in birds. Associated with acid deposition is an increase in aluminum availability due to solubilization from soil and other sources. (Conversely, experimental diets containing aluminum sulfate have much reduced pHs.) The present studies compare the effects of two levels of dietary acid (sulfuric acid) (0.122 and 0.56 mol H+ per kg feed; 0.056 and 0.277 mol sulfate per kg feed) and dietary aluminum (aluminum sulfate at 0.1 and 0.5%; sulfate at 0. 056 and 0.277 mol sulfate per kg feed) on bone growth, mineralization, and phosphorous/calcium homeostasis in growing birds (chickens and mallard ducks). Growth was reduced by the high acid (chicken) and aluminum (ducks and chickens) diets. A reduction in bone mineralization was observed in birds receiving aluminum-containing diets [low aluminum diet: decreased tibia ash, calcium, and phosphorus (chickens); high aluminum diet: decreased tibia dry weight, % of ash and mg; ash, calcium (chickens, ducks as % of ash), and phosphorus (chickens mg/duck, % of ash)]. Moreover, plasma concentrations of inorganic phosphate were reduced in chicks on the high aluminum diet. There were also marked decreases in bone growth and mineralization [tibia weight, ash (mg), calcium (mg), phosphorus (mg)] and plasma concentrations of 1,25-dihydroxy vitamin D3 in chicks on the high acid diet compared to those on a control diet. These changes were probably due to reduced feed intake; changes in bone indices being of a greater or similar magnitude in pairfed control. There was little change in bone indices, growth rate or feed consumption in ducklings receiving either the low or high acid diets. It is concluded that aluminum directly adversely affected bone mineralization whereas acid effects are mediated in part by changes in feed consumption.

Acids↗

PubMed1997

Prevention of duodenal ulcer recurrence with 15 mg lansoprazole: a double-blind placebo-controlled study. The Lansoprazole Study Group.

Although eradication of Helicobacter pylori cures duodenal ulcer, some patients are not infected and others are treatment failures. This randomized, double-blind, placebo-controlled study assessed the value of treatment with low-dose lansoprazole in preventing duodenal ulcer recurrence. One hundred eighty-six patients with endoscopic documentation of healed duodenal ulcer received 15 mg/day lansoprazole or placebo for 12 months or until ulcer recurred. Endoscopy results, symptom assessment, and fasting serum gastrin levels were obtained at multiple time points. Densities of E, EC, and G cells were assessed by biopsy when the ulcer recurred or at the final visit. Time to ulcer recurrence was significantly longer (P < 0.001) in the lansoprazole group (median >12 months) compared to placebo (median <3 months), and patients taking lansoprazole were asymptomatic longer (P < 0.05). Maintenance therapy with lansoprazole 15 mg/day suppresses acid and controls recurrence of duodenal ulcer disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1997

Constitutive mRNA and immunoreactivity for IL-2 in human nasal mucosa.

BACKGROUND: The nasal mucosa is the initial site in the upper airway of host defence against antigenic challenge in the form of airborne allergens, irritants, toxins and infectious agents, and yet little is known about nasal mucosal cytokine expression and function. We hypothesized that IL-2 might play a role in immunocompetence of the upper airway. METHODS: IL-2 immunoreactivity was measured by ELISA in nasal secretions and by Western blot. Immunohistochemistry and electron microscopy were performed on turbinated tissue. mRNA for IL-2 was evaluated by RTPCR and Southern hybridization. RESULTS: IL-2 immunoreactivity was demonstrated by Western blot and quantitated by an enzyme immunoassay. Immunohistochemical and electron microscopy analysis of turbinate tissue revealed interstitial staining for IL-2. By RTPCR, IL-2 message was evident in 5/5 atopics and 5/5 non-atopics. IL-2 message was expressed in all subjects by Southern hybridization to an internal probe after PCR. CONCLUSION: This study has demonstrated constitutive expression of IL-2 protein and mRNA in the upper airway of healthy individuals. The further characterization of cytokines in the upper airway could provide useful insights into immune regulation at the mucosal level.

Base Sequence↗

PubMed1995

Prospective multicenter evaluation of an initially placed button gastrostomy.

Eight-six patients were prospectively evaluated following placement of the One-Step gastric button. Placement problems, most commonly caused by the stoma measurement device, were noted in 17%. In an additional 30% of patients, peristomal infection, leakage, or migration developed within the first 90 days of placement. The authors conclude that although this gastric button can be placed in the majority of patients, potential design and placement problems may produce significant intraprocedural and postprocedural complications.

Gastrostomy↗

PubMed1995

Selecting a bedside glucose monitor for outpatient clinics.

The purpose of this study was to determine the accuracy of two bedside capillary blood glucose monitors that were being considered for purchase for an adult outpatient clinic. Participants were 101 patients 18 years or older with a diagnosis of diabetes mellitus who were attending medical service outpatient clinics. Participants were randomly assigned to two groups for bedside glucose measurement. Clinic nurses trained for the study did the bedside glucose readings and all venous blood samples were analyzed in the hospital's clinical laboratory. Results of t tests indicate a statistically significant difference between the bedside capillary and venous glucose levels for the total sample (p < or = 0.001). The difference between bedside capillary glucose and venous glucose within monitor groups for bedside capillary glucose and venous glucose was also statistically significant (p < or = 0.001) for both groups. The mean percentage difference between the venous (reference) readings and bedside capillary glucose reading was 8.3% for the Accu-Easy and 12.4% for the Glucometer Encore. This between-monitor group percentage difference was statistically significant (p < or = 0.001). Regression equations generated from patient data then used to predict venous glucose values from bedside capillary glucose values indicate variability in the accuracy of the monitors, especially in the higher ranges, which could result in undertreatment of hyperglycemia.

Bias↗

PubMed1994

Utilization and cost analysis of bedside capillary glucose testing in a large teaching hospital: implications for managing point of care testing.

PURPOSE: To study the use and cost of bedside capillary glucose testing in a large teaching hospital. PATIENTS AND METHODS: In a prospective study of 40 inpatient units and 10 outpatient units at Massachusetts General Hospital, records were maintained by each unit of the date, time, operator, and results of patient and quality control tests. Cost analysis was performed using data from time studies, test tallies in logbooks, and hospital administration records. RESULTS: The number of glucose meters in the hospital increased from 10 to 54 over a 2-year period. In 1992, 67,596 tests were performed by the bedside method, representing 30.7% of all glucose measurements performed in the institution. The majority of tests (94.7%) were performed on inpatients, and 10.2% of all hospital admissions underwent bedside glucose testing. The impact on the number of glucose tests performed in the clinical laboratories was minimal, indicating that bedside glucose testing was added as an extra test rather than as a substitute for laboratory-based glucose measurements. The cost of bedside glucose testing was $4.19 per test compared with $3.84 in the clinical laboratory. The cost varied from one unit to another (median $5.52, range $3.08 to $48.16), an effect largely attributed to the difference in the volume of tests performed by different units. In seven high-volume units the cost per test was lower than the corresponding value in the laboratory. The cost of bedside glucose testing included labor (80.2%) and supplies (19.8%). The percent of costs attributed directly to patient testing was 57.7%, whereas the costs for all other related activities (training, quality control, and quality assurance) was 42.3%. CONCLUSIONS: Bedside capillary glucose testing is a rapidly expanding technology and is performed on a significant percentage of hospital admissions. Bedside glucose testing is not inherently more expensive than centralized laboratory measurements but implementation on inefficient care units with low utilization can add substantially to the cost. Much of the excess cost of the bedside method can be attributed to the high costs of quality control and quality assurance, training, and documentation.

Blood Glucose↗

PubMed1994

Double-blind comparison of lansoprazole, ranitidine, and placebo in the treatment of acute duodenal ulcer. Lansoprazole Study Group.

OBJECTIVES: To study in a double-blind controlled manner the effects of lansoprazole 15 mg or 30 mg daily compared with ranitidine 300 mg once daily and placebo in the relieving of symptoms and healing of acute duodenal ulceration. METHODS: Two hundred eighty patients with duodenal ulcer entered in to the study from 30 centers. They were randomized in a double-blind manner into four groups with 80 patients entered into each active treatment group and 40 patients into the placebo group. Endoscopy was performed at 2- and 4-wk intervals to assess healing. Symptom relief was recorded, serum gastrin levels were measured, and gastric mucosal biopsies were obtained to evaluate for the presence of acute and chronic inflammation, the presence of neoplasia, and the extent of gastric endocrine growth at the time of endoscopy. RESULTS: After 4 wk of treatment using per protocol analysis, 19 of 40 (47.5%) patients receiving placebo had healed compared with 55 of 78 (70.5%) receiving ranitidine (p < 0.05 vs. placebo), 61 of 76 (80.3%) receiving lansoprazole 30 mg (p < 0.05 vs. placebo), and 72 of 78 (92.3%) receiving lansoprazole 15 mg (p < 0.05 vs. placebo and ranitidine). In patients with evaluable data, lansoprazole 30 mg and ranitidine produced greater relief of night-time symptoms and lansoprazole 15 mg produced greater relief of both day- and night-time symptoms than did placebo after 4 wk of treatment. Ranitidine increased fasting serum gastrin levels (22%; p < 0.05 vs. placebo), whereas both lansoprazole regimens produced more marked rises in serum gastrin (54% and 60%; p < 0.05 vs. placebo and ranitidine). Lansoprazole 15 mg and 30 mg also increased the density of antral G-cells (105.8% and 128.80%; p < 0.05 vs. baseline) and greater curvature Grimelius-positive cells (20.33% and 28.8%; p < 0.05 vs. baseline); there were no increases in the density of antral EC- or D-cells, and there was no alteration of gastric endocrine growth as judged by the Solcia classification. Both ranitidine and lansoprazole were associated with decreased antral Helicobacter pylori density accompanied, in the lansoprazole groups, by decreased antral inflammation scores. All antisecretory regimens were associated with increased inflammatory scores in the greater curvature. CONCLUSIONS: In acute duodenal ulceration, treatment with lansoprazole 15 and 30 mg produced 4-wk healing rates and symptom relief superior to those produced by placebo and the 15-mg dose similar to those produced by placebo. The 15-mg dose of lansoprazole was also superior to ranitidine in healing duodenal ulcer after 4 wk of therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1992

Airway epithelial cell mucin release: immunologic quantitation and response to platelet-activating factor.

Mucus production is an integral component of airway mucosal inflammation. Platelet-activating factor (PAF) is a phospholipid mediator implicated in the pathogenesis of many inflammatory processes, including airway inflammation. PAF functions as a mucus secretagogue when mucus is quantitated as radiolabeled glycoconjugates released from airway organ cultures. To more directly assess the interaction of PAF and airway epithelial mucous cell secretion, we used primary feline tracheal epithelial cell cultures and an immunoassay for a specific mucous cell secretory vesicle component. Cultured tracheal epithelial cells were shown to synthesize and secrete glycoconjugates with mucin characteristics. These mucin-type glycoconjugates were immunoreactive with a mucous cell-specific antibody. Localization of this antibody to components of the secretory vesicles of cultured epithelial cells was confirmed by electron microscopic immunogold labeling. Using this monoclonal antibody, an immunoassay was developed to quantitate release of immunoreactive material into cell culture media. Exposure of cultures to PAF produced a concentration-dependent, prompt release of immunoreactive material. Concentration-dependent inhibition of this effect was demonstrated by coincubation with the PAF receptor antagonists, WEB 2086 and Ro 19-3704. A component of the signal transduction pathway for PAF effects was studied in cultured tracheal epithelial cells by coincubation of PAF with nordihydroguaiaretic acid (NDGA), a combined lipoxygenase and cyclooxygenase inhibitor, or p-bromophenacyl bromide (BPB), an inhibitor of cellular arachidonic acid release. Both NDGA and BPB blocked PAF-stimulated mucin release in a concentration-dependent manner. These studies demonstrate a direct airway epithelial mucous cell secretagogue effect that appears to be dependent upon airway epithelial PAF receptors and altered cellular lipid metabolism. These findings suggest a direct and potent mechanism for goblet cell secretion during airway inflammation.

Animals↗

PubMed1991

Distribution of type X collagen in tibiotarsi of broiler chickens with vitamin D deficiency.

Type X collagen is a significant component of the extracellular matrix of the hypertrophic zone of physeal cartilage, but its precise role in endochondral ossification has not been determined. The concentration of type X collagen increases in physeal cartilage in chicks with vitamin D deficiency. The purpose of our study was to determine whether defective endochondral ossification due to vitamin D deficiency was associated with abnormalities in the distribution of type X collagen in the proximal tibiotarsus of chicks. To accomplish this, we induced vitamin D deficiency in broiler chicks and sequentially evaluated the pattern of type X collagen immunoreactivity in the proximal tibiotarsus using a monoclonal antibody specific for chicken type X collagen. Type X collagen immunoreactivity was present in the matrix of the prehypertrophic zone, hypertrophic zone, cartilage cores of the primary spongiosa, and within the chondrocytes of the prehypertrophic and early hypertrophic zones in vitamin D-deficient and D-replete chicks. However, rachitic chicks exhibited two consistent differences in type X collagen immunoreactivity: hypertrophic chondrocytes in the late hypertrophic zone and primary spongiosa contained intracellular type X collagen; and type X collagen was concentrated into laminated aggregates in the pericellular and territorial matrices in the late hypertrophic zone and primary spongiosa.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗

PubMed1991

The relationship of early versus two-minute recovery echocardiographic values following maximal effort resistance exercise.

Two-dimensionally directed M-mode echocardiography was used to measure left ventricular systolic function following maximal dynamic resistance exercise (RE). Upright measurements were made from the long axis parasternal view at rest, 20 seconds post-exercise, and two minutes post-exercise. Thirty-two successful studies were recorded from a total of 37 trained and untrained male subjects who were heterogeneous as to mode and level of training. Resistance-trained men averaged 3.8 +/- 2.4 yrs of training for 9.7 +/- 3.0 hr/wk, and endurance-trained men averaged 6.4 +/- 3.9 yr of training at 202.5 +/- 112.6 km/wk of cycling, running, and swimming. The trained men competed at the state or regional level. The RE protocol (knee extensions) was performed as follows: Set 1 (10 s rest) Set 2 (10 s rest) Set 3 60% 1-RM@8 reps 60% 1-RM@8 reps 60% 1-RM to fatigue. The RE protocol produced significant post-exercise reductions in end-systolic diameter (p less than 0.0002) and significant post-exercise increases in fractional shortening (p less than 0.0001) and velocity of circumferential fiber shortening (p less than 0.0002). The inotropic variables were still significantly different at two minutes post-exercise compared to the 20 second measure, suggesting that early recovery is a better approximation of maximal values. Velocity of circumferential fiber shortening at 20 seconds and two minutes was significantly correlated (r = 0.39) and fractional shortening was not (r = 0.34) at these serial measurement times.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Substance P and neurokinin A in human nasal mucosa.

The tachykinins substance P (SP) and neurokinin A (NKA) were studied in human inferior turbinate nasal mucosa by radioimmunoassay, immunohistochemistry, and autoradiography and for their effect upon mucus release in an in vitro culture system in order to infer their potential functions in the upper respiratory tract. Similar amounts of SP (1.03 +/- 0.12 pmol/g wet weight; mean +/- SEM; n = 26) and NKA (0.76 +/- 0.23; n = 7) were found. NKA and SP immunoreactive nerve fibers were found in the walls of arterioles, venules, and sinusoids and as individual fibers in gland acini, near the basement membrane, and in the epithelium. [125I]SP bound to arterioles, venules, and glands. [125I]NKA bound only to arterioles. In short-term explant culture of fragments of human nasal mucosa, both 1 microM SP and 1 microM NKA stimulated release of [3H]glucosamine-labeled respiratory glycoconjugates. These results indicate that SP and NKA have similar distributions in nociceptive sensory nerves in human nasal mucosa. The distribution of [125I]SP binding sites is consistent with a role for SP as a vasodilator and mucous secretagogue. The presence of [125I] NKA binding sites on vessels suggests a primary role for NKA in regulating vasomotor tone.

Amino Acid Sequence↗

PubMed1991

Use of a monoclonal antibody enzyme-linked immunosorbent assay to measure human respiratory glycoprotein production in vitro.

High-molecular-weight glycoprotein from human airway cultures was used to generate murine monoclonal antibodies, one of which recognizes a high-molecular-weight, hyaluronidase-resistant glycoprotein localized by immunofluorescent microscopy and immunogold electron microscopy to the secretory granules of human airway submucosal gland mucous cells and goblet cells. This monoclonal antibody was used to develop an enzyme-linked immunosorbent assay (ELISA) that was adapted to the study of respiratory glycoprotein secretion from human airways in vitro. Using the assay, the effect of a known mucus secretagogue, the cholinergic agonist methacholine, was studied on explant cultures of tissue from human bronchus or from human nasal mucosa. In studies of human bronchus explants, methacholine, 100 and 10 microM, stimulated increased secretion of respiratory glycoprotein (RGP) by 109 +/- 8% (n = 14; P less than 0.001) and 96 +/- 14% (n = 9; P less than 0.001), respectively, above control values. In studies of human nasal turbinate mucosal explants, methacholine, 100 and 10 microM, stimulated increased secretion of RGP by 75 +/- 28% (n = 7; P less than 0.01) and 70 +/- 21% (n = 4; P less than 0.01) above control values. An ELISA for the measurement of RGP secretion may provide a sensitive and more specific method for the performance of in vitro studies of RGP secretion from human tissues.

Animals↗