Search PubMed⌕ Search

Biomedical subjects

M D Stevens

Publications and source records attributed to M D Stevens.

17 recordsLinked to original sources
PubMed1994

Biological and kinetic characterization of recombinant human macrophage inflammatory peptides 2 alpha and beta and comparison with the neutrophil activating peptide 2 and interleukin 8.

We examined the biological and kinetic characteristics of two new members of the intercrine family of cytokines. Human macrophage inflammatory peptides 2 alpha and beta (huMIP-2 alpha and beta) were compared to human interleukin 8 (huIL-8), neutrophil activating peptide 2 (huNAP-2), and N-formyl-L-methionyl-L-phenylalanine (fMLP). The huMIP-2 peptides were the least potent cytokine tested in triggering neutrophil degranulation. They were also less potent neutrophil chemotaxins than fMLP or huIL-8. However, they were more effective than NAP-2 in stimulating chemotaxis of neutrophils. The binding studies showed that huMIP-2 peptides could interact with specific receptors on human blood neutrophils. Moreover, huMIP-2 peptides competed for up to 60% of the huIL-8 binding sites on neutrophils whereas huIL-8 competed for almost 100% of either of the huMIP-2 peptide binding sites. These data suggest the huMIP-2 peptides have little or no affinity for 40% of the huIL-8 receptors. In addition, detectable amounts of mRNA for huMIP-2 alpha were found in samples from human alveolar macrophages stimulated with Staphylococcus aureus, toxic shock syndrome toxin-1 (TSST), but not in samples stimulated with S. aureus enterotoxin A (SEA) or Escherichia coli endotoxin (lipopolysaccharide = LPS). In conclusion, huMIP-2 alpha and beta are weak neutrophil stimulating agents, which may increase inflammation in diseases such as toxic shock syndrome.

Bacterial Toxins↗
PubMed1993

Neutrophil-activating peptide-2 in patients with pulmonary edema from congestive heart failure or ARDS.

We carried out studies to determine whether the neutrophil-activation peptide-2 (NAP-2) plays a role in the recruitment and/or degranulation of neutrophils into the lungs of patients with the adult respiratory distress syndrome (ARDS) or congestive heart failure (CHF). NAP-2 precursors plus NAP-2 (beta-thromboglobulin-like antigen) were measured in lung fluids and plasmas with a radioimmunoassay, and NAP-2 was separated from its precursors by high-performance liquid chromatography. Pulmonary edema fluids (PEFs) from patients with CHF contained higher concentrations of the beta-thromboglobulin-like antigen than PEFs from patients with ARDS, and bronchoalveolar lavage fluids (BALs) from patients with ARDS contained higher concentrations of beta-thromboglobulin-like antigen than BALs from normal subjects. beta-Thromboglobulin-like antigen concentration was 4.1-fold greater in PEFs from patients with CHF than in their plasmas. Chemotactically active NAP-2 was also demonstrated in PEFs but not in plasmas from patients with CHF and ARDS. These data suggest that significant platelet degranulation occurred into the lungs of the patients with CHF and that NAP-2 and other platelet constituents may contribute to fluid formation in patients with CHF.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Generation of the neutrophil-activating peptide-2 by cathepsin G and cathepsin G-treated human platelets.

The neutrophil-activating peptide-2 (NAP-2) is a cytokine that is generated by the proteolytic cleavage of a precursor protein and that causes neutrophil degranulation and chemotaxis. NAP-2 precursors are produced in platelets and are normally found in the circulation. We showed that NAP-2 is generated by the action of neutrophil cathepsin G on two of the precursors, the connective tissue-activating peptide-III (CTAP-III) and beta-thromboglobulin (beta-TG). However, neutrophil elastase degraded the precursors to inactive peptides. The specific binding of cathepsin G to platelets caused the platelets to secrete NAP-2, and cathepsin G bound to the platelets could still generate NAP-2 from its precursor proteins. In addition, activated neutrophils in the presence of platelets generated NAP-2 from its precursors and caused platelets to secrete NAP-2. These studies demonstrate a unique mechanism for the activation of neutrophils through the interaction of neutrophils, platelets, and NAP-2 precursors that are released either by activated platelets or are present in circulation. It is therefore possible that NAP-2 may be generated at sites where aggregations of neutrophils and platelets occur in vessels such as pulmonary capillaries in patients with the adult respiratory distress syndrome and coronary arteries in patients with evolving myocardial infarctions.

Blood Platelets↗
PubMed1989

Search for drugs that may reduce the load of neutrophil azurophilic granule enzymes in the lungs of patients with emphysema.

Neutrophil elastase and myeloperoxidase probably play an important role in the development of pulmonary emphysema. We have analyzed drugs from the major classes of agents that alter neutrophil function to determine if there are drugs in use today that can reduce the load of neutrophil elastase or myeloperoxidase in the lungs of smokers. Eleven representative drugs were tested for their ability to inhibit chemotaxis and degranulation. None of the drugs inhibited chemotaxis in a dose-response fashion at concentrations achievable in human plasma. Sulfinpyrazone, phenylbutazone, and auranofin completely inhibited the release of azurophilic granules (myeloperoxidase) and tertiary granules (beta-D-glucuronidase) when formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) was used as the stimulant, and inhibited azurophilic granule release by 69%, 19%, and 64% respectively, but not tertiary granule release when macrophage-conditioned media was used as the stimulus. In conclusion, none of the drugs tested are inhibitors of chemotaxis; however, three are excellent inhibitors of azurophilic granule enzyme release. Of these three, sulfinpyrazone, a drug that is not currently used clinically for its antiinflammatory effects, is the least toxic and should be considered as a potential drug to reduce the elastase and myeloperoxidase load in the lungs of smokers who are developing emphysema.

Anti-Inflammatory Agents↗
PubMed1987

Maintenance of normal circulating levels of delta 4-androstenedione and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates: evidence for a servo-control mechanism.

To study the effect of obesity on the metabolism of adrenal androgens not bound to testosterone-estradiol-binding globulin, the MCRs of delta 4-androstenedione (A) and dehydroepiandrosterone (DHEA) were determined using constant infusion of unlabeled steroids to steady state in 8 normal weight and 19 obese nonhirsute eumenorrheic women. The blood production rates (PR) were calculated as the product of the MCR and the 24-h integrated serum concentrations (IC). The mean MCR and PR of A and DHEA were significantly higher in the obese women than in the normal weight women. There was, however, no difference in the mean IC of each androgen in the 2 groups. The MCR and PR of A and DHEA were each correlated with the body mass index (BMI; kilograms per m2). The MCR and PR of A and the MCR of DHEA were also correlated with the ratio of waist circumference to hip circumference (WHR). However, the PR of DHEA was not correlated with WHR. There was no correlation between the IC of either androgen and BMI or WHR. However, partial correlation analysis revealed that correction of the BMI for WHR resulted in a significant negative correlation between BMI and IC of A. We conclude that the MCR and PR of A and DHEA were increased in obese nonhirsute eumenorrheic women; there was a strong correlation between BMI and the MCR and PR of A and DHEA; upper segment obesity, as measured by WHR, was correlated with the MCR and PR of A and the MCR of DHEA, but not with the PR of DHEA; and circulating DHEA and A were maintained at normal levels in the obese eumenorrheic women despite an increase in the MCR, which suggests that a servo-mechanism is operative which registers the body size and adjusts the PR according to the MCR.

Adult↗
PubMed1986

Relative sensitivity and responsivity of serum cortisol and two adrenal androgens to alpha-adrenocorticotropin-(1-24) in normal and obese, nonhirsute, eumenorrheic women.

The alpha ACTH-(1-24) threshold dose and the response slope were determined for cortisol (F), delta 4-androstenedione (A), and dehydroepiandrosterone (DHEA) in 10 normal and 16 obese eumenorrheic nonhirsute women matched for age. Each woman received 1 mg dexamethasone at 2300 h and again at 0700 h the next morning. At 0700 h, a continuous alpha ACTH-(1-24) infusion was begun at an initial dose of 30 ng/1.5 m2 body surface area X hr. The ACTH infusion rate was doubled every hour for 5 consecutive h to a maximum dose of 480 ng/1.5 m2 X h. Blood samples were collected for steroid assays before the infusion and at the end of each hour. The ACTH threshold dose was defined as the dose that produced a steroid response significantly above the basal level. The ACTH threshold dose for serum F and DHEA stimulation was not different between the groups, but the threshold dose for A was significantly lower in the obese women. Basal and stimulated serum DHEA to F ratios were significantly higher in the obese women. In both groups, the mean F response slope was significantly higher than that for DHEA, which in turn, was significantly higher than that for A. The mean DHEA response slope was significantly greater in the obese women. The F and A response slopes were not different between the groups. We conclude that the relative responsivity of the steroids to ACTH was the same in both groups: F greater than DHEA greater than A; in the obese women, the ACTH threshold dose for F stimulation was lower (greater sensitivity) than for DHEA or A stimulation; and in the obese women, the ACTH threshold dose for A was significantly lower (increased sensitivity) and the slope of the DHEA response to ACTH was steeper (greater responsivity) than in normal women.

Adrenal Cortex Function Tests↗
PubMed1984

Specific receptor for ceruloplasmin in membrane fragments from aortic and heart tissues.

Membrane fragments from aortic and heart tissues of immature chicks were observed to bind highly purified, 125I-labeled chick ceruloplasmin. The binding reaction exhibited a linear Scatchard plot for both tissues and showed for each an apparent dissociation constant (Kd) of about 10(-8) M. On the basis of Scatchard analyses, aorta contained 1.5 pmol of receptors/mg of membrane protein, whereas receptors in the membranes from heart tissue were at least 5 times more dense. The binding of chick ceruloplasmin to aorta membranes was trypsin sensitive and neuraminidase insensitive, and showed both saturation and reversibility. Various sialoglycoproteins in 500 molar excess had very little effect on the binding. The asialo derivatives of these proteins likewise did not inhibit the binding. Human ceruloplasmin was found to bind very weakly to the chick membranes. Asialo chick ceruloplasmin bound with the same efficacy as native chick ceruloplasmin. Heat-denatured chick ceruloplasmin, however, was very ineffectual in displacing native 125I-ceruloplasmin from the membranes. These studies provide the first evidence for a homologous membrane receptor for native ceruloplasmin in the plasma membranes of animal cells.

Animals↗
PubMed1982

Autoradiographic evidence for a calcitonin receptor on testicular Leydig cells.

Previous studies have indicated that there is a relation between testicular function and adequate concentrations of zinc in testicular cells, and that calcitonin alters cellular zinc transfer in the testis. The present studies provide autoradiographic evidence that calcitonin binds in vivo to the cell membrane of testicular Leydig cells. The data thus confirm the presence of the testicular cell membrane calcitonin receptors that were previously demonstrated indirectly by Scatchard analysis of data collected from binding studies.

Animals↗
PubMed1980

Influence of parathyroid hormone and calcitonin on tissue zinc homeostasis in the rat.

Tissue zinc accumulation kinetics and compartmental analysis models were evaluated in thyroparathyroidectomized (TPTX) rats treated with parathyroid extract or calcitonin. The animals were injected with 65Zn and studied at multiple time intervals. SAAM-25 was utilized to generate models from the plasma specific activity decay curves. Calcitonin had a marked effect to decrease the fractional influx and efflux transfer coefficients in the model and inhibit tissue zinc accumulation in several, but not all, tissues. Parathyroid extract increased accumulation in all tissues studied, but had minimal effects on the model. It is concluded that parathyroid hormone acts nonspecifically and that calcitonin appears to have specific influences on zinc homeostasis.

Animals↗
PubMed1979

Tumor-host responses to various nutritional feeding procedures in rats.

Parenteral and enteral nutrition are being used as adjuncts to cancer therapy. A liquid diet formulation containing a 27% solution of glucose and 3.9% crystalline amino acids with electrolytes and vitamins was given continuously for a week via parenteral (iv), and via intragastric (ig) routes and also was given ad libitum via the oral or per os (po) route to groups of Buffalo rats with and without a Morris No. 7777 transplantable hepatoma to find out how these feeding procedures affect tumor-host interactions. Other groups of rats with and without the hepatoma were given solid food ad libitum. The following parameters were examined: mortality, carcass and organ weights, body and tumor growth, nitrogen balance, energy intake, fluid balance, urinalysis, hematology values, and serum protein levels. The results are considered with respect to the influence of the tumor on the host and the influence of the feeding procedure on the animal with and without a tumor. The presence of the hepatoma was associated with: higher mortality, a decrease in carcass mass, leucocytosis, anemia, a decrease in serum IgG, transferrin and albumin, and an increase in serum alpha fetoprotein. The iv and ig feeding procedures alone resulted in some mortality which was exacerbated by the presence of the tumor. Mortality was especially high in the tumorous rats on the ig feeding procedure. The degree of positive nitrogen balance and carcass mass was similar in non-tumorous rats fed the same liquid diet formula when given iv, ig, or po. Tumorous rats fed the liquid diet ad libitum showed anorexia and a significantly lower nitrogen balance. The iv and ig feeding of tumorous rats at a level which was well above those of the tumorous rats given solid or liquid diet ad libitum maintained the same degree of positive nitrogen balance as non-tumorous rats. Even though the iv feeding of tumorous rats maintained about the same degree of positive nitrogen balance as non-tumorous rats, these tumorous rats still suffered loss of carcass mass. It appears that the large rapidly growing hepatoma has priority for available nutrition over the host. It is further suggested that the rapidly growing hepatoma places an ever increasing demand on the available nutrients. Thus, a point is eventually reached where even supplemental nutritional support can no longer meet the needs of the growing hepatoma and the host.

Animals↗
PubMed1976

Comparative analysis of community health planning: transition from CHPs to HSAs.

With the implementation of the National Health Planning and Resources Development Act, comprehensive health planning is moving into a new phase. In search of lessons to guide future planning efforts on the part of the Health Systems Agencies (HSAs) established by the act, this paper reviews organizational and operational characteristics of ten relatively "successful" local comprehensive health planning agencies. Several problems are delineated that HSAs will likely share with their predecessors and strategies for confronting these problems are suggested.

Community Participation↗
PubMedDate not supplied

Satellite digital display for the Clinac-18.

A satellite digital display of the gantry and collimator positions has been mounted on the Clinac-18 console. This module provides simultaneous digital readout of the gantry angle, collimator rotation angle, upper-jaw position, and lower-jaw position. Continuous display of these parameters during the treatment is important in minimizing patient treatment errors.

Data Display↗
PubMedDate not supplied

Computer interface for a linear accelerator.

A computer interface for the Clinac-18 linear accelerator has been developed, using a standard CAMAC interface plus buffer amplifiers to isolate the CAMAC from the accelerator electronics. Buffer amplifiers are employed because direct connection of the CAMAC system to the accelerator was found to affect accelerator operation. The total interface accommodates the four gantry position analog signals and thirteen digital signals describing all available treatment options. The interface also allows the computer to inhibit beam operation.

Computers↗