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Biomedical subjects

S K Young

Publications and source records attributed to S K Young.

At least 37 records · Page 2Linked to original sources
PubMed1996

Induction of Th1 cytokine responses by mycobacterial antigens in leprosy.

Twelve mycobacterial antigens were compared for induction of gamma interferon (IFN-gamma) secretion by human blood mononuclear cells of patients with leprosy. Fractionated Mycobacterium leprae antigens containing cell wall proteins or cytosolic and membrane proteins induced good IFN-gamma responses in tuberculoid leprosy patients. Lipoarabinomannan from M. tuberculosis Erdman and M. leprae mycolylarabinogalactan peptidoglycan were the poorest IFN-gamma inducers.

Antigens, Bacterial↗
PubMed1996

Tumors of minor salivary glands and the analysis of 106 cases.

This study is based on 106 cases of predominantly minor salivary gland tumors which were received at the University of Oklahoma College of Dentistry Department of Oral Pathology Biopsy Service from 1972 to 1995. (In this study), 55% of the cases were benign and 45% were malignant. Benign tumors include pleomorphic adenoma (68%), monomorphic adenoma (10%), oncocytoma/oncocytosis (7%), papillary cystadenoma (14%), and myoepithelioma (2%). Of the malignant tumors, 34% were mucoepidermoid carcinoma, 17% adenoid cystic carcinoma, 21% adenocarcinoma, not otherwise specified (N.O.S.), 21% polymorphous low-grade adenocarcinoma, and 6% malignant mixed tumors. There was no difference in relative incidence of benign or malignant tumors between males and females. The 7th decade was the peak occurrence age for both benign and malignant and the palate was the most frequent location.

Adolescent↗
PubMed1995

Divergence in macrophage insulin-like growth factor-I (IGF-I) synthesis induced by TNF-alpha and prostaglandin E2.

Increased synthesis of insulin-like growth factor I (IGF-I), a fibroblast growth factor, is induced in murine macrophages by TNF-alpha. TNF-alpha also induces macrophages to express cytocidal activity, but only during costimulation with IFNs. Since prostaglandin E2 (PGE2) is known to inhibit macrophage cytocidal activity, its possible reciprocal enhancement of IGF-I synthesis was examined. PGE2 or dibutyryl cyclic AMP (dbcAMP) stimulated the synthesis of IGF-I similarly to TNF-alpha in magnitude and time course. TNF-alpha did not increase IGF-I synthesis by first inducing PGE2 synthesis, because indomethacin was unable to block the effect of TNF-alpha. PGE2 did not stimulate IGF-I synthesis by first inducing TNF-alpha production, because 1) anti-TNF-alpha Ab did not block PGE2-induced IGF-I synthesis, and 2) PGE2 down-regulated TNF-alpha mRNA levels and did not affect levels of the cytokine in supernatants. Moreover, the difference in the induction of IGF-I was observed at the level of signal transduction, in that PGE2 and dbcAMP increased cAMP-dependent protein kinase (PKA) activity, whereas TNF-alpha stimulated the mitogen-activated protein (MAP) kinase pathway. Divergence between the two pathways was also noted in the regulation of IGF-I at the mRNA level, and an additive effect on IGF-I synthesis was observed when cells were incubated with the combination of TNF-alpha plus PGE2 or dbcAMP. Collectively, these data suggest that TNF-alpha and PGE2 stimulate IGF-I synthesis in macrophages by two separate pathways, and that PGE2 acts as a positive stimulus for IGF-I synthesis through a cyclic AMP/PKA pathway.

Animals↗
PubMed1995

Paradoxic effect of ibuprofen on neutrophil accumulation in pulmonary and cutaneous inflammation.

Evidence exists to suggest that the local accumulation of neutrophils in pulmonary inflammation occurs by a different mechanism than in other microvascular beds. In the present study, this suggestion was investigated using the nonsteroidal antiinflammatory drug ibuprofen. This drug was used because in addition to inhibiting cyclooxygenase, it prevents several aspects of neutrophil function, including adhesion. Local inflammation in the lung and skin of the same rabbits was induced by the administration of C5a, and the effect of intravenous injection of ibuprofen on the accumulation of neutrophils at these two sites was examined. In the skin, neutrophil accumulation was inhibited by ibuprofen, and this appeared to be independent of cyclooxygenase blockade. A possible mechanism was prevention of neutrophil adherence to endothelium in postcapillary venules, and in vitro experiments showed that ibuprofen could entirely prevent neutrophil adherence, in addition to suppressing azurophil granule secretion and superoxide anion generation. However, the effect on adherence appeared to be independent of expression of the CD11/CD18 adhesion complex on the neutrophil. By contrast, in the pulmonary circulation of the same rabbit, C5a-induced neutrophil accumulation was enhanced by ibuprofen treatment. This was suggested to result from the prevention of thromboxane production, which normally serves to decrease local pulmonary blood flow to diminish delivery of neutrophils to the inflammatory site. Ibuprofen had no effect on retention of neutrophils in filters (models of pulmonary capillaries), suggesting that the drug was not enhancing the retention of neutrophils in capillaries on the first pass through the lung. Thus, it was possible that enhancement in the lung was caused by an increase in neutrophil supply. Because the accumulation of neutrophils in the skin is known to be dependent on the adherence phenomena, the paradoxic effects of ibuprofen on inflammation suggest that mechanisms responsible for the accumulation of neutrophils in cutaneous and pulmonary microcirculations are different.

Animals↗
PubMed1995

Agriculture-related injuries in the parkland region of Manitoba.

OBJECTIVE: To review a series of farm injuries in the parkland region of Manitoba, compare the collected data to similar studies, and provide a baseline for deriving effective preventive measures for the local community. DESIGN: Retrospective case study involving review of hospital charts. SETTING: The population studied was derived from the catchment area for Dauphin General Hospital, a referral centre servicing an agricultural region of 57,000 people. PATIENTS: Seventy-two patients were admitted to hospital between January 1981 and December 1991 after being injured by agricultural machines, farm animals, herbicides or other chemicals, and fertilizers. Four fatalities were identified through a review of local medical examiner records, for a total of 76 cases. MAIN OUTCOME MEASURES: The following data were abstracted for each case: sex, age, time and date of injury, cause, type of injury, and body part involved. RESULTS: Most cases involved men, between the ages of 20 and 69, during the afternoon and early evening with a seasonal peak in late summer. More than 60% of injuries were caused by agricultural machinery, followed by animal-related injuries (25%). Grain augers were the most common type of machine causing injury (35%). All patients younger than 9 years were female, and 75% of their injuries involved farm animals. A decreasing annual frequency of farm injuries was noted over the 11-year period. Fewer accidents involving farm machinery appear most responsible for this trend. CONCLUSIONS: Many agriculture-related injuries occur in the parkland region of Manitoba. The type and pattern of injuries observed resembles those documented in other studies. With effective education and preventive measures, most injuries and fatalities could be prevented. Physicians are obliged to encourage and support educational programs in their communities and to review safety practices with patients.

Adolescent↗
PubMed1994

Disparate role of the beta 2-integrin CD18 in the local accumulation of neutrophils in pulmonary and cutaneous inflammation in the rabbit.

The leukocyte adhesion glycoprotein complex CD11/CD18 has been shown to be important in mediating neutrophil accumulation at sites of inflammation in many experimental models. The exception is the lung, where neutrophil accumulation into the airspaces can be CD18-dependent and -independent, according to the stimulus used to induce pulmonary inflammation. By using the anti-CD18 mAb 60.3, this study examined the role of CD18 on neutrophil accumulation in the lungs of rabbits induced by a local intrabronchial instillation of C5a or interleukin-1 alpha (IL-1 alpha) into the upper lung lobes. For comparison, cutaneous inflammation was induced in the same animals by intradermal injection of the same mediators. Pretreating rabbits with 60.3 abolished accumulation of 111In-labeled neutrophils in skin induced by both C5a and IL-1 alpha. In contrast, in the same animals, C5a-induced accumulation of neutrophils in the lung was not significantly affected by 60.3, while neutrophil accumulation in response to IL-1 alpha showed a significant, but not absolute, dependency on CD18. External gamma scintigraphy of 111In-labeled neutrophils demonstrated that the kinetics of cell retention in the lung was similar for both C5a and IL-1 alpha. In summary, accumulation of neutrophils to sites of inflammation in cutaneous inflammation shows an absolute dependency on CD18, while migration of these cells to sites of inflammation in the lung can be largely independent of this adhesion molecule. These data indicate that the mechanisms responsible for accumulation of neutrophils in cutaneous and pulmonary inflammation are different.

Animals↗
PubMed1992

Engineering design of vascular prostheses.

The replacement and bypass of arteries of diameter greater than 6 mm with textile vascular prostheses has proved very successful since they were first introduced forty years ago. Although manufacturers continue to improve their products and make them of consistent quality for increased safety and performance and to facilitate their use by surgeons, most of the research work in this area is concerned with the development of small-diameter prostheses. Current expanded PTFE and textile prostheses do not perform satisfactorily when their diameters are reduced to less than 6 mm. For the small-diameter prostheses it will be necessary to develop less thrombogenic materials and to design the structure of the prostheses more closely to match the mechanical properties of the natural arteries. The purpose of this paper is to discuss the design requirements and to review the development of large- and small-diameter vascular prostheses.

Biocompatible Materials↗
PubMed1991

In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus.

Twenty-one papillomas, 23 ordinary benign keratoses, 13 smokeless tobacco keratoses, 10 verrucous hyperplasias, 10 verrucous carcinomas, 17 squamous cell carcinomas, 3 epithelial dysplasias, and 6 lichen planus lesions were evaluated for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/35, with biotinylated double-stranded DNA probes by in situ hybridization. Sixty-two percent (13/21) of oral squamous papillomas were positive for HPV DNA. HPV DNA types 6 and 11 demonstrated the strongest reactivity. Of the 13 cases, 10 also showed some reactivity with HPV-16/18 and -31/33/35. None of the cases of keratoses, epithelial dysplasia, squamous cell carcinoma, verrucous hyperplasia, verrucous carcinoma, or lichen planus were positive for HPV DNA. This study confirms the consistent and frequent finding of HPV DNA in oral squamous cell papillomas and the inconsistency of being able to identify HPV DNA in keratotic, premalignant, or cancerous lesions of the oral mucous membranes.

Carcinoma, Papillary↗
PubMed1991

Factors related to failure of structural bone grafts in acetabular reconstruction of total hip arthroplasty.

Structural bone grafts in acetabular reconstruction of total hip arthroplasty have come into more common usage with the increasing number of revision arthroplasties. The authors present the outcome of 40 bone grafts with follow-up periods of 2-8 years. Primary and revision arthroplasties with both cemented and noncemented fixation are included. Factors that had a statistically significant relationship to failure of the bone graft included fit and fixation of bone graft to host, fit and fixation of prosthesis to host, union of bone graft to host, and the presence or absence of the confluence of the anterior and posterior columns of the acetabulum. Other findings of interest were a higher failure rate of multiple grafts as compared to a single graft and freeze-dried femoral heads. Migration of the socket of more than 3 mm is statistically related to failure of the socket.

Acetabulum↗
PubMed1991

Biophysical properties and microfilament assembly in neutrophils: modulation by cyclic AMP.

The microfilament lattice, composed primarily of filamentous (F)-actin, determines in large part the mechanical (deformability) properties of neutrophils, and thus may regulate the ability of neutrophils to transit a microvascular bed. Circulating factors may stimulate the neutrophil to become rigid and therefore be retained in the capillaries. We hypothesized that cell stiffening might be attenuated by an increase in intracellular cAMP. A combination of cell filtration and cell poking (mechanical indentation) was used to measure cell deformability. Neutrophils pretreated with dibutyryl cAMP (db-cAMP) or the combination of prostaglandin E2 (PGE2, a stimulator of adenylate cyclase) and isobutylmethylxanthine (IBMX, an inhibitor of phosphodiesterase) demonstrated significant inhibition of the n-formyl-methionyl-leucyl-phenylalanine (fMLP)-inducing stiffening. The inhibition of cell stiffening was associated with an increase in intracellular cAMP as measured by enzyme-linked immunoassay (EIA) and an increase in the activity of the cAMP-dependent kinase (A-kinase). Treatment with PGE2 and IBMX also resulted in a decrease in the F-actin content of stimulated neutrophils as assayed by NBD-phallacidin staining and flow cytometry or by changes in right angle light scattering. Direct addition of cAMP to electropermeabilized neutrophils resulted in attenuation of fMLP-induced actin assembly. Neutrophils stimulated with fMLP demonstrated a rapid redistribution of F-actin from a diffuse cortical location to a peripheral ring as assessed by conventional and scanning confocal fluorescence microscopy. Pretreatment of neutrophils with the combination of IBMX and PGE2 resulted in incomplete development and fragmentation of the cortical ring. We conclude that assembly and redistribution of F-actin may be responsible for cell stiffening after exposure to stimulants and that this response was attenuated by agents that increase intracellular cAMP, by altering the amount and spatial organization of the microfilament component of the cytoskeleton.

1-Methyl-3-isobutylxanthine↗
PubMed1990

The subcellular distribution of platelet-activating factor in stimulated human neutrophils.

Exposure of human peripheral blood neutrophils to a variety of phagocytic and soluble stimuli is known to induce the synthesis and secretion of platelet-activating factor (PAF), a unique ether-linked phospholipid. It has recently been observed in this laboratory, that whereas some PAF is secreted to the exterior of the cell, the majority of the newly synthesized PAF is retained intracellularly. This observation led us to investigate the subcellular distribution of intracellular PAF in stimulated human neutrophils, and to question the possible intracellular role of this molecule. Approximately 2 x 10(8) neutrophils were exposed to either the phagocytic stimulus, opsonized zymosan particles (25 particles/cell), the soluble stimulus, Ca2(+)-ionophore A23187 (5 micrograms/ml), or were left unstimulated for up to 30 min. After disruption, the cells were fractionated into nuclei, phagolysosomes, specific granules, azurophil granules, membranes, and cytosol. Fractions were analyzed for representative organellar markers, as well as for total protein, total phospholipid phosphorous, and PAF. In cells that had been exposed to opsonized zymosan particles, the majority of the PAF was localized to the phagolysosomal fraction, with lesser amounts being detected in the membranous and granular fractions of the cells. In neutrophils that had been exposed to A23187, the major portion of the PAF was detected in the membranous fractions with smaller amounts being seen in fractions corresponding to the specific granules. On the basis of these data, combined with the known physicochemical properties of PAF, it is speculated that the PAF detected at discrete intracellular locations in stimulated human neutrophils may play an important role in the endocytic and/or secretory functions of neutrophils.

Calcimycin↗
PubMed1990

Medium-chain-triglyceride lipid emulsion: metabolism and tissue distribution.

The utilization and distribution of radioactively labeled lipid emulsions were evaluated in Sprague-Dawley rats. Animals received one of three lipid emulsions. Group 1 received [14C]medium-chain-triglyceride (MCT) lipid emulsion, group 2 received a 75%:25% (vol:vol) admixture of [14C]MCT: unlabeled long-chain-triglyceride (LCT) lipid emulsion, and group 3 received only [14C]LCT. The radioactive dose appearing in expired carbon dioxide and various body tissues was monitored over a 24-h period. Results indicate that MCT is oxidized more rapidly and completely than in LCT; approximately 90% of the MCT is converted to carbon dioxide with in 24 h compared with 45% for LCT. When MCT and LCT are administered together, the metabolism of MCT is slowed but remains more rapid than that of LCT. Removal of MCT from the blood was more rapid than was removal of LCT, and tissue radioactivity was lower.

Animals↗
PubMed1990

Interaction between chemoattractants and bacterial lipopolysaccharide in the induction and enhancement of neutrophil adhesion.

Chemotactic peptides in the circulation stimulate neutrophils to become sequestered in the pulmonary vasculature, and low concentrations of bacterial lipopolysaccharide (LPS) enhance and prolong this effect. This interaction of neutrophils with the vascular endothelium is thought to involve, in part, the increase in adhesiveness induced in neutrophils by such stimuli. In this study, the binding of albumin-coated latex beads to neutrophils was used to determine whether the enhancement seen with LPS results from an increase in the number of adhesive cells, from the enhancement of the adhesiveness of individual neutrophils, or both. Chemotactic peptides alone and LPS alone induced an increase both in the adhesive population and in the number of beads bound per individual neutrophil. The number of beads bound per cell increased over a very wide range of stimulus concentrations, showing that the degree of adhesiveness of an individual cell in the population varies over a considerable range. Trace concentrations of LPS (10 ng/ml or less), i.e., levels close to those measurable in vivo, had little effect on the proportion of neutrophils that were stimulated by chemotactic factor to become adhesive but did significantly enhance the number of beads bound to each individual neutrophil. The enhancement may require the presence of the CD11/18 glycoprotein complex, but was not further upregulated by LPS. No evidence could be obtained to suggest that the effect of LPS involved release of tumor necrosis factor (TNF) from the numbers of monocytes in the preparation, and the observations are consistent with a direct effect of LPS on the neutrophils. It is suggested that this increase in adhesive sites on the cell could explain the persistence of the sequestration of neutrophils in the microvasculature seen in the presence of both chemoattractants and LPS by enhancing the "strength" of the adhesion to endothelial cells. The increased adhesion may also set the stage for enhanced endothelial injury.

Antigens, CD↗
PubMed1990

Control of bleeding in cemented arthroplasty.

Bleeding from cancellous bone causes lamination within bone cement and at its prosthetic interfaces, and weakens the fixation of joint replacements. We examined the effects of anaesthesia and blood pressure on bleeding in human cancellous bone, and investigated the local response to freezing saline, 1:200,000 adrenaline and hydrogen peroxide. Spinal anaesthesia reduced cancellous bleeding by an average of 44%, local freezing saline by 24%. Saline at room temperature, adrenaline solution and hydrogen peroxide each reduced it by 14%. The effects of spinal anaesthesia and of freezing saline were additive: used together they reduced bleeding by 56%. The reduction of blood contamination of cement and its interfaces should contribute to better prosthetic fixation.

Anesthesia, Conduction↗
PubMed1989

Familial gigantiform cementoma: classification and presentation of a large pedigree.

Very few cases of gigantiform cementoma have been reported, and those associated with a positive family history are especially rare. Confusion exists about the relationship of gigantiform cementoma to florid osseous dysplasia, cementifying fibroma, and diffuse chronic sclerosing osteomyelitis. It has been unclear whether gigantiform cementoma should be accorded the status of a separate entity. In this article, we report our findings on a family that, over five generations, has exhibited clinical, radiographic, and/or histologic findings consistent with the designation familial gigantiform cementoma. This pedigree consists of 55 members. Significant heterogeneity in expression of this trait was noted. The pattern of occurrence of the trait is consistent with an autosomal dominant mode of inheritance with variable expressivity of the phenotype. We suggest that familial gigantiform cementoma should be recognized as a separate entity.

Cementoma↗
PubMed1989

Competitive effects of long-chain-triglyceride emulsion on the metabolism of medium-chain-triglyceride emulsions.

This study was conducted to assess the potential metabolic competitive interactions of intravenous medium-chain-triglyceride (MCT) and long-chain-triglyceride (LCT) lipid emulsions. To assess this competition increasing concentrations of LCT emulsion were added to an intravenous dose of MCT emulsion of 3.0 g/kg body wt up to a maximum dose of 3.0 g LCTs/kg body wt. Blood samples were assessed for competitive interactions by analyzing the following metabolites: glucose, insulin, lactate, pyruvate, ketones (acetoacetate, beta-hydroxybutyrate), elimination of triglycerides, and free fatty acids. Evaluation of the data showed a strong competitive interaction between the MCT and LCT emulsions. This competition was evident as soon as LCTs were added to the MCT infusions and appeared to favor LCTs for removal and metabolism over MCTs. This appears to indicate that there is a peripheral, strong affinity site for LCT removal and metabolism and a shared peripheral site and specific visceral site for MCT removal and metabolism.

Animals↗