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Biomedical subjects

W M Burch

Publications and source records attributed to W M Burch.

At least 37 records · Page 2Linked to original sources

Triiodothyronine stimulates cartilage growth and maturation by different mechanisms.

The mechanisms by which triiodothyronine (T3) stimulates growth and maturation of growth-plate cartilage in vitro were studied by incubating embryonic chick pelvic cartilages in serum-free medium in the presence and absence of T3 for 3 days. To determine whether T3 might stimulate production of somatomedins by the cartilage, medium from cartilage incubated with and without T3 was assayed for somatomedin C (Sm-C) by radioimmunoassay. No difference in Sm-C content was found. However, cartilage incubated with T3 and increasing amounts of human Sm-C (0.5-20 ng/ml) weighed more and had greater amounts of glycosaminoglycan than cartilage incubated in the same concentrations of Sm-C without T3, suggesting that T3 enhances the growth effect of somatomedin. We added a monoclonal antibody to Sm-C (anti-Sm-C) to the organ culture to determine whether T3's stimulatory effect on cartilage growth could be blocked. The anti-Sm-C inhibited growth of cartilage incubated in medium alone and blocked the growth response to T3. By using alkaline phosphatase as a biochemical marker to follow maturation, we found that T3 stimulated a 57% increase in alkaline phosphatase activity above cartilage incubated in medium alone and that anti-Sm-C did not inhibit T3's stimulatory effect on alkaline phosphatase activity. We propose two different mechanisms by which T3 affects growth-plate cartilage: T3 promotes cartilage growth primarily through enhancing the effect of somatomedin, and T3 stimulates cartilage maturation possibly by accelerating the normal process of cartilage differentiation from proliferative to hypertrophic chondrocytes.

Animals↗

Distributions of an ultra-fine 99Tcm aerosol and 81Krm gas in human lungs compared using a gamma camera.

A 99Tcm aerosol of particle size 0.12 micron and the gas 81Krm were administered to four normal subjects and to eleven patients with airway disease. Posterior-anterior gamma camera images of erect lungs were compared qualitatively and quantitatively, and 99Tcm clearance rates were measured. Qualitatively the two images were similar in normal subjects but differed in most patients owing to small regions of high count density in the 99Tcm images. In a few patients, regional variations in ventilation were defined more finely by the aerosol. In both groups a significant vertical gradient in 99Tcm count density relative to 81Krm count density was found. Penetration of 99Tcm to the lung periphery relative to the hilar region was similar to that of 81Krm in the normal subjects and less than that of 81Krm in the patients. Possible causes of the differing distributions are discussed. The images obtained with the aerosol in the two groups studied were similar to those reported for larger particle aerosols.

Adult↗

Technegas--a new ventilation agent for lung scanning.

A simple process using technetium-99m generator eluate in a graphite crucible at 2500 degrees C, produces a structured ultra-fine dispersion of labelled carbon. Particle sizes are 5.0 nm (0.005 micron) and less and adhere to the walls of the alveoli on inhalation. Penetration characteristics are gas-like and the radioactivity per litre of carrier argon allows single breath inhalations of a diagnostic dose. Over 190 patients have been studied including 50 within a formal clinical trial with xenon-133. Results of tomography, dynamic inhalation, and image subtraction using this new agent-'Technegas'--are presented.

Carbon↗

Embryonic chick cartilage produces its own somatomedin-like peptide to stimulate cartilage growth in vitro.

Embryonic chick pelvic cartilages increase in size and weight when incubated in a chemically defined medium in the absence of serum. We addressed the question of whether endogenous production of growth factors by the cartilage was responsible for this growth. We found that conditioned medium, in which pelvic cartilages from 9-day-old chick embryos had been incubated for 3 days, increased cartilage dry weight 32% over weights of cartilages incubated in fresh medium. Increasing concentrations of conditioned medium stimulated cartilage weight and proline incorporation in a dose-dependent manner. To determine the molecular size(s) of potential growth-stimulating factors, conditioned medium was dialyzed at acid pH, lyophilized, and fractioned over HPLC-TSK Spherogel 3000. The collections were pooled into five fractions (greater than 100K, 30-100K, 20-30K, 12-20K, 1-12K, and less than 1K). Each fraction was readded to organ culture, and growth was assessed 3 days later. Only the 1-12K fraction stimulated growth above that of control cartilage. We assayed cartilage and conditioned medium for somatomedin-C (Sm-C) by RIA to determine if Sm-like peptides were present. Although Sm-C was not detectable within the cartilage, it was readily measurable in concentrated medium (248 +/- 35 pg/ml). Since Sm-like peptides might play a functional role in the growth process, we used a monoclonal antibody to Sm-C to determine whether immunoneutralization of the Sm-like peptides would inhibit cartilage growth in vitro. Addition of anti-Sm-C to organ culture of chick cartilage prevented increases in cartilage wet and dry weights (only 16% and 0%, respectively, above preincubation weights). The inhibitory effect of anti-Sm-C could be reversed by the addition of high doses of insulin to the medium. These studies suggest that endogenously produced Sm-like peptides have a functional role in promoting cartilage growth and support the hypothesis that growth factors may regulate growth through autocrine mechanisms.

Animals↗

Lung ventilation studies with technetium-99m Pseudogas.

Technetium-99m Pseudogas is an ultrafine near monodisperse aerosol of 0.12-microgram diam particle size. This report describes initial clinical experiences with 27 patients referred for investigation of suspected pulmonary embolism, and in whom Pseudogas ventilation images were compared with a high quality commercial aerosol. An additional group of ten patients with severe COPD was examined in a comparative trial of Pseudogas with 81mKr. Pseudogas was better than a conventional aerosol in reaching a diagnosis of pulmonary embolism using a simple blinded comparison with coded images. In addition, bronchial deposition was minimal unless COPD was severe. Moderately well patients had no difficulty inhaling the necessary activity in one or two breaths, and even severely ill and frail aged persons could accomplish the passive breathing maneuver in less than a minute. Clearance of Pseudogas was directly to the systemic circulation with a half-time of 10 min in normal subjects extending up to 100 min in patients with airways disease.

Adolescent↗

Malignant teratoma in the thyroid gland of an adult: a case report and a review of the literature.

Teratomas in the neck are rare neoplasms. Most occur in the neonate and are benign. In contrast, cervical teratomas in adults are malignant and carry a poor prognosis. Fourteen adult cases have been reported in the world literature, and 11 of these were stated to have arisen in the thyroid gland. A case of a 27-year-old man who presented with a large goiter is reported. A preoperative diagnosis of a malignant thyroid mass was suggested by clinical examination, needle aspiration, and computerized tomography. The patient had a subtotal debulking thyroidectomy. The pathologic specimen confirmed a primary malignant teratoma of the thyroid gland. Despite a combination of radiotherapy and chemotherapy, which were well tolerated, the patient died 2 months after surgery.

Adult↗

Phosphotyrosine and phosphoprotein phosphatase activity of alkaline phosphatase in mineralizing cartilage.

We used embryonic skeletal cartilage known to have high levels of alkaline phosphatase activity to determine whether growing cartilage has phosphotyrosine phosphatase activity and phosphotyrosinyl histone phosphatase activity at physiologic pH. Embryonic chick pelvic cartilage and fetal pig scapular growth-plate cartilage were assayed using phosphotyrosine as substrate at pH 7.5 and the amount of tyrosine generated measured. Both cartilage models had Km for phosphotyrosine between 6 to 24 mus mol/L. Phosphotyrosine phosphatase activity correlated with alkaline phosphatase activity as assessed by (1) distribution of histologic staining for alkaline phosphatase within the cartilages, (2) hormonal stimulation of cartilage alkaline phosphatase activity in vitro, (3) comparison of alkaline phosphatase and phosphotyrosine phosphatase activities in the presence of known inhibitors (vanadate, levamisole, homoarginine, and zinc), and (4) assaying chick epiphyseal cartilage alkaline phosphatase purified to homogeneity for phosphotyrosine phosphatase activity. Areas of cartilage with elevated alkaline phosphatase activity also had raised phosphotyrosine phosphatase activity. Triiodothyronine, a known stimulator of cartilage alkaline phosphatase, increased chick cartilage alkaline phosphatase activity 88% and phosphotyrosine phosphatase activity 106%, and stimulated porcine growth-plate cartilage alkaline phosphatase activity 91% and phosphotyrosine phosphatase activity 145% after 3 days of in vitro incubation. Each of the inhibitors block alkaline phosphatase and phosphotyrosine phosphatase activities. The purified alkaline phosphatase had a Km for phosphotyrosine of 18 mus mol/L and Vmax of 5700 nmol tyrosine/mg protein/h, which is well over 1000-fold higher than the phosphotyrosine phosphatase activity found in the above preparations of pelvic and scapular cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Calcitonin stimulates maturation of mammalian growth plate cartilage.

To determine whether calcitonin (CT) might effect maturation of mammalian growth plate cartilage, we administered salmon CT (sCT) to young rats and used the growth plate from the distal metatarsal as our in vivo growth plate model. Growth plate alkaline phosphatase activity and histological examination were assessed after 3 days of sCT treatment. Alkaline phosphatase activity, a marker of hypertrophied chondrocytes, increased 85%, and the zone of maturation enlarged in rats receiving sCT. In addition, sCT treatment was associated with an increased growth plate 35SO4 incorporation 84% above animals receiving buffer alone. We tested whether this might be a direct effect of CT by using an in vitro model, the growth plate from the fetal pig scapula. Organ culture of these cartilages in serum-free medium with and without sCT (1 U/ml) was performed for 3 days. sCT stimulated alkaline phosphatase activity 49% above growth plates incubated in medium alone. Furthermore, sCT treatment increased the number of hypertrophied chondrocytes leading to widening of the zone of maturation. These studies suggest that CT might have a role growing mammals by promoting maturation of growth plate cartilage.

Alkaline Phosphatase↗

Homologous and heterologous growth hormones fail to stimulate avian cartilage growth in vitro.

Recent reports that GH has a direct effect on growing cartilage have raised questions as to the role of somatomedins (Sm) in cartilage growth. To test the hypothesis that GH directly stimulates cartilage growth, we added homologous and heterologous GHs to organ cultures of embryonic chick pelvic cartilage. Pelvic rudiments from 9-day-old chick embryos were incubated in serum-free medium for 3 days in medium alone or medium containing chicken GH, turkey GH, bovine GH, human GH, and bovine GH produced by recombinant DNA methodology. None of the GH preparations studied stimulated avian cartilage growth in vitro. However, cartilage wet weight increased in response to sera from normal and growth hormone-treated hypophysectomized rats. In addition, 20 ng/ml purified Sm-C caused a 78% increase in cartilage weight above that of cartilage incubated in medium alone. Insulin also caused an increase in cartilage weight, but in concentrations 50,000-100,000 times that of Sm-C. Our studies demonstrate that homologous and heterologous GH have no effect on growing avian cartilage and support the hypothesis that Sm directly mediate cartilage growth.

Animals↗

Cushing's disease. A review.

Cushing's syndrome continues to tax the most discerning clinician. I review pituitary-dependent adrenal hyperplasia (Cushing's disease), including recent experiences with Cushing's disease at Duke University, Durham, NC, and relate these observations to the current ideas as to pathophysiology, etiology, and management of Cushing's disease. Transsphenoidal microsurgery (TPS) performed by an experienced neurosurgeon offers selective removal of corticotropin (ACTH)-secreting adenoma, immediately cures the hypercortisolism, preserves pituitary function, and is associated with minimal morbidity. Postoperative hypoadrenalism appears to be the best marker of surgical cure. Transsphenoidal surgery has revolutionized our thoughts as to etiology and treatment of Cushing's disease, yet failures with TPS and uncertainty of recurrences leave room for radiotherapy, adrenalectomy, and adjunctive drug therapy in the management of this entity.

Adenoma↗

Hormonal stimulation of avian embryonic cartilage growth in vitro: histologic and ultrastructural features.

We studied the histologic and ultrastructural features of embryonic chick cartilage after the cartilage had been incubated in serum-free medium that contained hormones and growth factors known to stimulate in vitro cartilage growth. Pelvic cartilages from 9 d chick embryos were incubated in BGJb ( Fitton -Jackson modification) medium alone (control) or medium containing one of the following: N6 monobutyryl cyclic AMP 0.5 mM, forskolin 100 microM, triiodothyronine (T3) 10 nM, insulin 45 nM, or somatomedin C 0.67 nM. At the end of 3 d of incubation the cartilages were fixed in buffered formalin. Significant growth (increases in size, wet and dry weight) was seen with each treatment group. N6-Monobutyryl cAMP treated cartilage had an increased number of flattened immature chondrocytes with large nuclei and prominent nucleoli. The histologic and ultrastructural features of forskolin treated cartilage were indistinguishable from N6-monobutyryl cAMP treatment. The T3 treated cartilage contained large hypertrophic chondrocytes with prominent lacunar typical of mature cartilage. T3 treated cartilage had considerable vacuole formation and dilated endoplasmic reticulum. Insulin and somatomedin treated cartilage had histologic appearance similar to control cartilage. Thus, the effects of various hormones on embryonic cartilage growth in vitro can be separated as to whether growth is the result of chondrocytic hyperplasia (cyclic AMP mediated), chondrocytic hypertrophy with maturation (T3), or a combination of both hyperplasia and hypertrophy (insulin and somatomedin-C).

Animals↗

Technetium-99m 'pseudogas' for diagnostic studies in the lung.

Combustion of a flammable aerosol of 99Tcm generates an ultrafine aerosol of approximately 0.06 micron particle radius with a narrow log-normal distribution (omega g typically 1.25), close to monodisperse. Particles with this dimension do not settle out, but diffuse in a gas-like manner without aggregation. The name 'Pseudogas' has been given to this agent, to identify its unique characteristics. The technique for Pseudogas production is described and its physical properties analysed. Predicted behaviour is verified and illustrated by a clinical example. Small-airways retention of Pseudogas in normal lungs has an estimated half-time of about ten minutes, clearing to the systemic blood stream, but considerably extended regional and total times have been observed (up to 100 min) in some patients.

Aerosols↗

Calcitonin stimulates growth and maturation of embryonic chick pelvic cartilage in vitro.

To determine whether calcitonin (CT) affects the growth of avian embryonic skeletal tissue, pelvic cartilages from 9-day-old chick embryos were incubated in a serum-free medium containing CT for 3 days. Porcine CT (PCT), salmon CT (SCT), and human CT (HCT) stimulated increases in cartilage wet weight that were dependent upon the concentration of CT within the medium. Maximal growth was seen with PCT (1.0 U/ml), which increased cartilage wet weight 107% and dry weight 53% above those of cartilage incubated in medium alone. SCT (1.0 U/ml) and HCT (1.0 U/ml) stimulated a 55% increase in cartilage wet weight and a 20% increase in cartilage dry weight over those of cartilage incubated in medium alone. The reason for PCT's apparent potency was due to trace contamination of thyroid hormone in the PCT preparation, since synthetic PCT caused an increase in cartilage wet weight equivalent to those produced by SCT and HCT. Although each calcitonin increased wet and dry cartilage weights, the DNA content was not changed. Alkaline phosphatase activity, a marker of cartilage maturation, was found to be stimulated by CT. SCT, HCT, PCT, and synthetic PCT increased alkaline phosphatase activity over 2-fold above that in cartilage incubated in medium alone. Histological sections of CT-treated cartilage showed large round nuclei, vacuolated cytoplasm with lacuna formation, and an increased amount of cartilage matrix compared to those of cartilage incubated in medium alone. Thus, CT stimulates cartilage growth primarily through cellular hypertrophy and matrix formation. This study demonstrates that CT is a growth and maturation factor for avian embryonic cartilage in vitro.

Alkaline Phosphatase↗

Ia+ T cells in new onset Graves' disease.

The Ia (immune-associated, DR) antigen is a cell surface glycoprotein which is absent on normal circulating T lymphocytes but present on activated T lymphocytes. We studied the expression of this antigen on circulating T lymphocytes from patients with untreated hyperthyroid Graves' disease. All patients (n = 33) with recent onset hyperthyroid Graves' disease studied had an increased percentage and number of circulating Ia+ T cells. Patients with non-Graves's hyperthyroidism or Graves' disease patients more than 1 yr after thyroid ablation had normal values for Ia+ T cells. Other cell surface activation antigens, recognized by monoclonal antibodies 4F2 and 5E9, were not present on circulating T cells in patients with Graves' disease. The 100% positivity for increased numbers of Ia antigen-bearing T cells in hyperthyroid Graves' disease contrasts with our finding of 70% positivity in another HLA-DR-associated disease, recent onset type I diabetes mellitus. The pathogenic significance of these cells is not known, but they seem to represent selective activation of the immune system in patients with untreated hyperthyroid Graves' disease.

Adolescent↗