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Biomedical subjects

J Stevens

Publications and source records attributed to J Stevens.

At least 325 records · Page 18Linked to original sources

Synthesis and biological evaluation of Tc-99m N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate: a potential replacement for [131I]o-iodohippurate.

A new technetium-chelating agent based on amide and mercaptide donor groups, N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate, was synthesized as an analog of previously described N,N'-bis(mercaptoacetyl)ethylenediamine (DADS). Complexation of Tc-99m with the new chelating group resulted in two components that were separable by high-performance liquid chromatography. The component that eluted first demonstrated high specificity for renal excretion, with over 90% in the urine of rabbits at 35 min, 87% in the urine of mice at 2 hr, and 1.6% or less in the intestines of mice. Excretion was rapid, with the first component equaling or exceeding [131I]o-iodohippurate in the urine of rabbits at all times. The second or latter component demonstrated comparable specificity but slightly slower renal excretion kinetics. Clinical trials with the first component are probably warranted.

Alanine↗

Management of the deformed rheumatoid forefoot. A comparison of conservative and surgical methods.

In a retrospective survey of 65 patients who had rheumatoid arthritis, the late results of excision arthroplasty of the forefoot were investigated and compared with nonoperative management. Subjective assessment of foot shape and severity of pain as well as objective changes in gait and deformity were considered. Surgery relieved pain initially, but the recurrence rate of metatarsalgia was high. In those who wore surgical shoes, lack of cosmesis was the most important factor in determining poor compliance. The operation was recommended at random, and there was little difference in the outcomes of nonoperative and surgical treatments. A long-term randomized prospective trial is required to establish the criteria for selection of a management regime.

Adult↗

Insulin resistance in adipocytes from fed and fasted obese rats: dissociation of two insulin actions.

Adipocytes from 26-week-old Zucker rats (greater than 600 g) and controls of the same strain and age (greater than 400 g) served as models of insulin resistance and obesity. Adipocytes from fatty rats demonstrated insulin resistance of glucose metabolism and resistance to the antilipolytic effect of insulin which was not improved by fasting. Adipocytes from fatty rats were also resistant to the lipolytic action of norepinephrine. Control rats displayed insulin resistance of glucose metabolism and resistance to the antilipolytic effect of insulin. However, fasting for 6.5 days restored the antilipolytic action of insulin without affecting the insulin sensitivity of glucose metabolism. This dissociation of the responsiveness of insulin actions by fasting indicates that there may be at least two mechanisms of insulin resistance in the same cell.

Adipose Tissue↗

Orthopaedic aspects of Paget's disease.

Surgery may be indicated in the management of a patient with Paget's disease for a variety of reasons. These include diagnostic biopsy, correction of deformity of long bones and the treatment of fractures, secondary osteoarthritis and secondary tumours.

Bone Diseases↗

Immunochemical differences between glucocorticoid receptors from corticoid-sensitive and -resistant malignant lymphocytes.

We have explored the possibility of using antibodies against purified rat liver glucocorticoid receptors to study the immunochemical properties of glucocorticoid receptors from murine and human malignant lymphocytes. For this purpose, purified immune immunoglobulin G was covalently linked to Sepharose CL-4B. We then examined the ability of the affinity gel to recognize cytosolic [3H]triamcinolone acetonide-receptor complexes from the corticoid-sensitive (CS) and -resistant strains of mouse lymphoma P1798, from CS lymphocytes of patients with chronic lymphatic leukemia, and from a CS clone of human leukemic lymphoblasts in tissue culture (CH6). Mouse thymus was used as a source of glucocorticoid receptor from normal CS lymphocytes. Whereas the immunoaffinity column retained 70 to 84% of the 58- to 62-A (Stokes radius) [3H]triamcinolone acetonide-receptor complexes characteristic of the CS mouse and human lymphocytes, it failed to recognize the 27- to 28-A (Stokes radius) glucocorticoid receptor present in corticoid-resistant mouse lymphoma P1798 cells. Therefore, under appropriate experimental conditions, it was possible to demonstrate cross-reactivity between the antiserum against rat liver glucocorticoid receptor and the 58- to 62-A (Stokes radius) glucocorticoid receptor from species as diverse as mouse and humans.

Animals↗

Insulin-induced insulin resistance of lipolysis in human adipocytes in organ culture.

Adipose tissue derived from open biopsies was used to develop a system for studying insulin resistance in human tissue in vitro. Subcutaneous adipose tissue obtained from obese donors was incubated in Parker's medium 199 in the absence or presence of insulin for 24 h under sterile conditions. Adipocytes were then isolated by collagenase digestion, washed thoroughly, and incubated for 2 h with multiple insulin concentrations in Krebs-Ringer phosphate buffer with 4% bovine serum albumin. Lipolysis was estimated by measuring glycerol. Basal lipolysis in adipocytes cultured with insulin did not differ significantly from that of adipocytes cultured without insulin (2.49 +/- 0.18 vs. 2.67+/- 0.58 mumol glycerol/mmol triglyceride). The maximum acute response in adipocytes prepared from tissue exposed to insulin during culture was 55% inhibition of basal lipolysis, whereas the maximum response in cells prepared from tissue not exposed to insulin chronically was 80%. Statistical analysis by paired t test showed a significant difference (P < 0.01) in the reaction of the two groups of cells to acute exposure to insulin. The insulin dose required to produce the half-maximal effect was increased from 3 to 24 microU/ml. Thus, after chronic exposure to insulin, adipocytes were not as responsive to the acute antilipolytic action of the hormone. We conclude that chronic exposure to insulin induces insulin resistance in human adipocytes.

Adipose Tissue↗

Malignant hypertension revisited: the role of bilateral nephrectomy.

Hypertension is the leading cause of renal failure in this dialysis and transplant center. When malignant hypertension is encountered, the symptom complex of cachexia and failure to thrive highlights its clinical presentation. The courses of 32 black renal hypertensive patients studied retrospectively demonstrated this symptom complex as well as prolongation of survival, when bilateral nephrectomy and renal transplantation were used as definitive treatment.

Adolescent↗

High-performance liquid chromatographic analysis of emetine after oxidative activation to a fluorescent product.

A clinically useful analytical method is described for monitoring plasma levels of emetine. The drug is initially extracted from plasma with dichloromethane (0.3 volumes). The extract can be analyzed directly by paired-ion reversed-phase high-performance liquid chromatography to levels of 500 ng/ml of plasma by spectrophotometric monitoring of column effluent. For analysis of emetine at lower concentrations, the dichloromethane extracts are subjected to mild mercuric acetate oxidation prior to separation, thereby converting emetine to a fluorescent product. Spectrofluorometric monitoring of the column effluent readily extends the sensitivity of the assay to 10 ng of emetine/ml of plasma. At these levels measurements can be made with a precision of +/- 4%.

Chromatography, High Pressure Liquid↗