Transforming growth factor ß (TGF ß) is a multifunctional growth regulator with diverse biological effects, including promotion and inhibition of fibroblastic and epithelial cell growth, respectively (1, 2), chemotaxis of dermal fibroblasts and monocytes (3, 4), facilitation of extracellular matrix remodeling by fibroblastic cells (5-7), and effects on proliferation and function of T and B lymphocytes (8-10). These cellular responses appear pertinent to development and/or maintenance ofthe synovial panmus in inflammatory arthritis. Furthermore, subcutaneous injection of purified TGFP into newborn mice results in a multicellular response over 48-72 h (11), which is histologically similar to the synovial panmus seen in rheumatoid arthritis (RA). These findings led us to examine synovial effusions for the presence of TGFß.Volume 169 January 1989 291-296 Materials and Methods Brief Definitive ReportSynovial Fluids . Synovial fluids from the knees of 16 patients seen in the Vanderbilt University Rheumatology Clinic were collected by needle aspiration into heparin-free plastic syringes . Diagnoses determined by a rheumatologist included nine patients with RA, four with osteoarthritis, two with gout, and one patient with avascu1ar necrosis .Most fluids were routinely centrifuged at 1,200 g for 10 min at 4°C to remove cells . Some fluids were subjected to a more rigorous collection procedure involving centrifugation in plastic tubes at 5,000 g in a Sorvall high-speed centrifuge for 20 min, in order to minimize the possibility of contamination with platelet products released in vitro. The cell-and platelet-free supernatants were then collected with a glass pipette that was left in the tube at 37°C . Clotted material that formed around the glass pipette was discarded . The fluids were stored at -70°C until assay.Assaysfor 7GF--ß . A radioreceptor assay for TGF ß was performed using a previously described procedure (12) . Briefly, AKR-2B fibroblasts were plated in six-well culture plates at 1-2 x 105 cells per well using McCoy's 5A medium with 5% FCS . The next day, cells were washed three times with PBS and incubated for 2 h in the presence of 0 .25 ng of '2'I TGF p in 1 .0 ml of binding medium, with or without further additions. Nonspecific binding was determined by the addition of 1 gg of 50% pure unlabeled TGFP .After a 2-h incubation at room temperature with rocking, the cells were washed, released from the plate with collagenase, and cell-bound 125 1TGF-ß was measured in a gamma counter. Results were expressed as nanograms per milliliter TGF0 calculated from a standard curve (see Fig . 1) . The concentrations of TGF ß-competing activity in synovial fluids (Table I) were derived from triplicate determinations at a final dilution that would yield a 40-60% inhibition of binding.Two cell lines were also used in soft agar assays for TGF-ß . AKR-2B cells were assayed in the presence of serum as previously described (13) . Base layers of 0 .8% agar in McCoy's

The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

In a number of clinical conditions the response of the level of blood sugar to a given dosage of insulin is less than that obtained in normal individuals. This phenomenon is commonly termed insulin resistance. Soon after the discovery of insulin numlerous investigators described

No abstract

No abstract

No abstract

Electrolyte changes were studied during artificial respiration and hypothermia in dogs which had been equilibrated with K42, Na24 or B82. In the hypothermic animals potassium in plasma, potassium and sodium in skeletal muscle and potassium in auricle decreased, whereas bromide in the auricle increased. In normothermic animals anoxia produced an increase of bromide in the skeletal muscle and of sodium in the auricle; potassium increased in the plasma and decreased in the myocardium. Anoxia during hypothermia resulted in a loss of potassium from the contracting heart as the only significant change. Potassium to sodium ratios decreased more in the auricle than in the skeletal muscle in both hypothermia and anoxia. Thus, increased myocardial irritability during hypothermia and anoxia is caused or accompanied by a loss of potassium and an inability to extrude sodium.

A substance causing prolonged pressor effects in the rat has been demonstrated in crude protein-free extracts of hypertensive arterial blood (1). This material formed picrates which upon hydrolysis were further purified. Preliminary experiments indicated that a majority of the extracts of arterial blood taken from human hypertensive patients were pressor, while in only a few samples of blood taken from normotensive patients was such activity demonstrated. The present report is concerned with further demonstration of the presence of this vasoactive material and with the type of case in which it occurs (2-5), based upon experience with about 175 samples of blood. Subsequent reports will deal with methods of purification and analysis of chemical structure. The vasoactive substance was present in appreciable quantities in almost every case of hypertension having a nephrogenic component, was found in smaller amounts in cases of "neurogenlc" and "endocrine" hypertension, and was usually absent in cases of "malignant" hypertension. The finding that the "amine" level in hypertensive blood extracts is usually increased (1) has been confirmed.Because the substance differs from other known pressor agents and may represent a new naturally occurring compound of great activity, it has been accorded a name--pherentasin t (¢~po = hold up or bear up;~vra~ = pressure). Until chemical identification has been completed, pherentasin is defined as a substance detected by assay in rats, which induces a prolonged pressor response, contains an amine and a carbonyl group necessary for activity, is nonprotein in nature, and can be procured from the arterial blood of many hypertensive patients at concentrations of 1 to 20 ~ per liter.