Biomedical subjects
Publications and source records attributed to J Jennings.
A 2.5-year-old dog with congenital pulmonary valve dysplasia was treated by percutaneous balloon dilation of the stenotic orifice. Clinical and hemodynamic improvement was apparent immediately and for 9 months after the valvuloplasty procedure.
Skeletal growth factor (SGF) activity was extracted from human bone matrix by demineralization and purified under dissociative conditions using hydroxyapatite, HPLC gel-filtration and HPLC reverse-phase chromatography. Human SGF thus purified was characterized chemically and biologically. Purified human SGF stimulated chick embryo bone cell proliferation at picomolar concentrations (half maximum at 2-3 ng/ml) and had little or no activity on other cell types tested (mouse 3T3 and normal rat kidney fibroblasts, embryonic chick intestinal and human placental cells). Human SGF did not displace 125I-labeled epidermal growth factor binding to normal rat kidney cells and did not stimulate normal rat kidney cell colony formation in soft agar. Human SGF activity was sensitive to trypsin, chymotrypsin, papain, dithiothreitol and performic acid but was resistant to heat (upto 70 degrees C), pH (3-10), cyanogen bromide, alkaline phosphatase and neuraminidase and did not bind jack bean concanavalin A or kidney bean lectin. From our chemical and biological studies it appears that human SGF is different from other known polypeptide growth factors: epidermal growth factor, fibroblast growth factor, insulin, insulin-like growth factor-I, platelet-derived growth factor and transforming growth factor.
Blood and pleural effusion mononuclear cells from thirteen patients were examined for the expression of T lymphocyte differentiation antigens as well as in vitro thymidine incorporation. The ratio of T4 to T8 cells was significantly greater among pleural effusion lymphocytes than among blood lymphocytes. Effusion lymphocyte responses to phytohaemagglutinin were less than those of blood lymphocytes. Unstimulated thymidine incorporation was greater in pleural effusion lymphocytes. Antigen-stimulated lymphocyte reactivity was not consistently greater in either blood or effusion lymphocytes. Lymphocytes from tuberculous effusions all reacted to tuberculin. Pleural effusion lymphocytes, regardless of the etiology of the effusion, possessed the same range of antigenic specificities as did blood lymphocytes. Therefore, effusion lymphocyte responsiveness to tuberculin does not prove the presence of tuberculous pleurisy but does indicate sensitisation to tuberculin.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have compared the stimulation of sulfate and thymidine uptake into 10-day-old embryonic chick cartilage by normal human serum, partially purified somatomedins (Sm) A and B, homogeneous insulin-like growth factors (IGFs) I and II, and several other substances. With the exception of epidermal growth factor, all growth factors ((GFs) were assayed in the absence of other protein. Pelvic rudiments were preincubated in buffer for 6 h and then incubated for 24 h with the GF or serum, with labels added for the final 6 h. Human serum enhanced cartilage uptake of both thymidine and sulfate. There was a dose-dependent stimulation of thymidine uptake by Sm A or B (0.05--2 microgram/ml) and IGF I or II (0.5--20 ng/ml). Unlike serum, neither Sms nor IGFs increased SO4 uptake under these conditions. Bovine GH (10--500 ng/ml), albumin (100-1000 ng/ml), fibroblast GF (1--100 ng/ml), and epidermal GF (1--100 ng/ml) were inactive for both thymidine and sulfate. When a shorter incubation was used (7 h), Sm A enhanced SO4 uptake, and discrimination was increased by preincubation of the rudiments in buffer for 24 h. With this procedure, IGF I (0.5 ng/ml) was nearly equipotent to 5% serum. On a weight basis, IGF I was more active than either Sm A or IGF II. The data suggest that assay conditions are crucial for demonstration of Sm activity. Appropriate conditions may be different for isolated GF than for a complex medium such as serum. The results further suggest that with certain protocols, the responsiveness of chick embryo cartilage is qualitatively similar to that of hypophysectomized rat cartilage.
The embryonic chicken cartilage somatomedin bioassay was modified so that human serum stimulation of simultaneous [3H]methylthymidine and H2[35S]O4 incorporation could be assessed. The assay consisted of a 6 h pre-incubation of 10 day pelvic rudiments in enriched buffer, followed by a 24 h incubation with buffer and low (0.5, 2 and 5% v/v) serum concentrations. Both labels were present for the final 6 h. Other modifications were shortening of washing, elimination of drying and weighing, and simplification of digestion. Normal human serum produced a linear log dose-response with these serum concentrations. Potency ratios in patients with GH deficiency were less than those of normal adults for both thymidine 0.39 +/- 0.05 (mean +/- SEM, n = 16, range 0.22-0.71) vs. 0.90 +/- 0.05 (n = 19, 0.62-1.36, P < 0.001) and for sulphate 0.40 +/- 0.04 (0.15-0.65) vs. 94 +/- 0.05 (0.61-1.29, P < 0.001). Potency ratios for both labels rose following administration of a single dose (0.2 IU/kg im) of hGH to 4 GH deficient children. The reliability of prediction of GH deficiency, reproducibility, and precision were similar to other Sm bioassays. The major advantages of these modifications were the ability to examine 2 cartilage metabolic processes simultaneously and the small amount of serum (350 mul) necessary for patient assays.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of GH on cartilage may be mediated by a variety of serum factors (somatomedins; SM). We have reported (Endocrinology 90: 1086, 1972) stimulation of thymidine incorporation in isolated chicken embryo chondrocytes by normal human serum. This was greater than that caused by serum from patients with hypopituitarism. We have now compared the stimulatory activity estimated by [3H]thymidine incorporation (SMT) with that estimated by [3H]leucine incorporation in 46 sera from children with GH deficiency; with short stature, but normal GH responsiveness; or with normal stature and normal GH responsiveness. These activities were also measured in sera from 9 normal adults and 12 acromegalics. Sera from GH deficient children had reduced SMT activity (.54 +/- .04; (mean +/- SE) P less than .01) compared to normal children (.83 +/- .08) whereas the sera from children with short stature and normal GH responsiveness had higher levels than normal (1.19 +/- .10: P less than .02). Acromegalic adults averaged higher SMT activity than normal adults (1.62 +/- .15 vs. 1.17 +/- .11; P less than .05). In sharp contrast, the leucine incorporation was essentially the same in the different groups of children. These studies have validated the use of the incorporation of thymidine into isolated chicken embryo chondrocytes as an adjunct in the evaluation of children with short stature (82.6% of the samples from children gave results that were consistent with their status as determined by provocative tests for GH). The disparity between the results with thymidine incorporation and those with leucine incorporation is as yet unexplained.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.