PubMed Health⌕ Search

Biomedical subjects

S H Allen

Publications and source records attributed to S H Allen.

At least 37 records · Page 2Linked to original sources

Longstanding hyperprolactinemia associated with systemic lupus erythematosus: possible hormonal stimulation of an autoimmune disease.

OBJECTIVE: To describe 4 women in whom hyperprolactinemia was associated with the development of systemic lupus erythematosus (SLE). METHODS: Clinical assessment and followup (2 cases). Chart review and interviews with the attending rheumatologist (2 cases). Detailed review and reassessment of multiple imaging studies of the pituitary. RESULTS: One patient had idiopathic hyperprolactinemia, and 3 had pituitary microadenomas. Serum 17 beta-estradiol concentrations were normal in all women, but serum testosterone was suppressed in 2. SLE flares occurred in 2 individuals, one and 6 months after bromocriptine therapy was discontinued, and reinstitution of bromocriptine therapy in a patient who refused corticosteroids resulted in resolution of her SLE disease activity. CONCLUSION: Hyperprolactinemia, which has the potential to exacerbate autoimmunity, may coexist with SLE. In these instances, bromocriptine may afford therapeutic benefit.

Adult↗

Purification of alpha-fetoprotein from human cord serum with demonstration of its antiestrogenic activity.

Alpha-fetoprotein (AFP) was purified from pooled human cord serum to determine whether it would be similar to purified mouse AFP in its ability to be transformed into an antiestrogen by incubation with estradiol (E2). Greater purity was attained with a three-step purification procedure of chromatofocusing, Blue-Sepharose chromatography and immunoaffinity chromatography than with a two-step procedure of polyacrylamide gel electrophoresis followed by Blue-Sepharose chromatography. Nevertheless, both procedures rendered AFP in a form that was transformable by E2 to an antiestrogen, although the product of the three-step procedure afforded more consistent biological activity. Removal of albumin from AFP was crucial for transformation of AFP to an antiestrogen. Thus, human AFP is similar to mouse AFP in being transformed to an antiestrogen upon incubation with E2, even though there is only 66% structural homology between the two proteins, and human AFP lacks the high-affinity binding site for E2 present in the mouse AFP molecule.

Animals↗

Primary osteoporosis. Methods to combat bone loss that accompanies aging.

Osteoporosis is a major public health problem in the United States. The key to its management is prevention by ensuring adequate amounts of calcium, vitamin D, and protein and exercise throughout life. When a significant amount of bone mass has been lost, therapeutic interventions are aimed at preventing further loss with use of antiresorptive agents (ie, estrogen, progestin, calcitonin, and bisphosphonates). Use of pharmacologic agents that stimulate bone formation is still in experimental stages. Research efforts focusing on prevention, diagnosis, and treatment of osteoporosis are in progress and should provide improved strategies in the future.

Adult↗

Regulation of the Bacillus subtilis acetate kinase gene by CcpA.

The Bacillus subtilis gene encoding acetate kinase was identified on the basis of sequence similarity to the Escherichia coli ackA gene and to a second E. coli gene closely related to ackA. Insertional inactivation of this region of the B. subtilis chromosome resulted in the disappearance of acetate kinase enzyme activity in cell extracts. The ackA gene was mapped to a site close to the ccpA gene, at 263 degrees. The transcriptional start site for B. subtilis ackA was located 90 bp upstream from the start of the coding region, and expression was increased by growth in the presence of excess glucose. Growth of the AckA- mutant was inhibited by glucose, suggesting that acetate kinase is important for excretion of excess carbohydrate. The stimulation of ackA expression by glucose was blocked in a CcpA- mutant, indicating that CcpA, which is required for glucose repression of certain carbon source utilization genes, including amyE, may also be involved in activation of carbon excretion pathways. Two sequences resembling the amyO operator site were identified upstream of the ackA promoter; removal of this region resulted in loss of glucose activation of ackA expression.

Acetate Kinase↗

Effect of exercise on the bone mineral density and bone remodelling indices in women with rheumatoid arthritis: 2 case studies.

Two premenopausal women with rheumatoid arthritis of 16 years' duration were enrolled in a one year conditioning exercise program consisting of walking and low impact aerobics. The effect of exercise on the markers of bone formation (serum bone specific alkaline phosphatase and osteocalcin), bone resorption (urinary calcium/creatine and serum tartrate resistant acid phosphatase), and vertebral bone mineral density as determined by dual photon absorptiometry are discussed.

Absorptiometry, Photon↗

Calcinosis and metastatic calcification due to vitamin D intoxication. A case report and review.

Vitamin D, a fat-soluble vitamin, can be associated with significant morbidity when prescribed in large doses. We describe a hypoparathyroid patient with vitamin D intoxication who developed painful periarticular calcinosis, nephrocalcinosis with hypertension and chronic renal failure in addition to band keratopathy and hearing loss. He was treated with combination therapy including prednisone, phosphate-binding antacid, phenytoin and disodium etidronate. After 20 months of follow-up there was a significant reduction of periarticular calcinosis, but no improvement in renal function, band keratopathy or hearing loss and possible calcification of the ossicles. The clinicopathologic features of metastatic calcification and the various treatment modalities are reviewed.

Adult↗

Purification and characterization of human bone tartrate-resistant acid phosphatase.

Tartrate-resistant acid phosphatase (TRAP) is a histochemical marker for osteoclasts, the multinucleated bone resorbing cell. This type 5 acid phosphatase has been purified 500-fold from human bone by three chromatographic steps: cation exchange, gel filtration, and HPLC cation exchange. Like most other TRAPs isolated, it is a basic glycoprotein of a molecular weight about 33,000. Its pH optimum Km, and Vmax for p-nitrophenyl phosphate are 5.7, 0.8 mM, and 12 units/mg, respectively. Human bone TRAP hydrolyzes aryl phosphates, nucleoside di- and triphosphates, pyrophosphate, and phosphoproteins. It is activated by mild reducing agents but inhibited by molybdate, fluoride, arsenate, phosphate, and dithionite. Its activity is not inhibited by tartrate, a feature that distinguishes it from other acid phosphatases. Sodium etridonate, the bisphosphonate used clinically to reduce bone resorption, is a relatively poor inhibitor of bone TRAP. Human bone TRAP is immunologically related to the porcine uterine secretory TRAP, uteroferrin. Monospecific rabbit antibodies to the bone TRAP have been immunopurified by using affinity chromatography with uteroferrin immobilized on Sepharose and can be used to detect low amounts of the enzyme in a simple dot-blot assay.

Acid Phosphatase↗

The role of magnesium and potassium ions in the molecular mechanism of ribosome assembly: hydrodynamic, conformational, and thermal stability studies of 16 S RNA from Escherichia coli ribosomes.

In an attempt to understand the role of magnesium ion in ribosome assembly in vitro, the hydrodynamic shape, conformation, and thermal stability of ribosomal 16 S RNA were studied systematically as a function of Mg2+ concentration by sedimentation velocity, intrinsic viscosity, circular dichroism, and difference ultraviolet absorption spectroscopy. These results were then compared with the corresponding parameters obtained for 16 S RNA under the optimal conditions of reconstitution, i.e., at 37 degrees C, 20 mM Mg2+, an ionic strength equal to 0.37, and pH 7.8 [S. H. Allen, and K.-P. Wong (1978) J. Biol. Chem. 253, 8759-8766]. When the 360 mM KCl required for reconstitution of 30 S ribosomes is added to the medium, only subtle conformational changes are observed, consistent with the destabilization of the conformation, thus making the RNA molecule more "open" and accessible to protein binding. However, when the concentration of Mg2+ is lowered from 20 to 1 mM, the hydrodynamic parameters indicate that the 16 S RNA is partially unfolded, while thermal denaturation studies suggest that the amount of base-stacking and base-pairing is not concomitantly altered. Further removal of the Mg2+ by dialysis against a pH 7.8 buffer containing no Mg2+ results in a drastic decrease of secondary structure and indicates that the Mg2+ is required for maintenance of the pairing, stacking, and stability of the nucleotide bases, in addition to the long range interactions which result in a compact structure. The results suggest that the 20 mM Mg2+ is required for the 16 S RNA molecules to assume the proper secondary and tertiary structure containing the protein-binding sites, while the high K+ concentration (360 mM KCl) is needed for "loosening up" the RNA, making the protein binding sites more accessible to the ribosomal proteins for molecular recognition and binding as well as for the conformational changes that occur during ribosome assembly.

Circular Dichroism↗

Antepartum reversal of hematologic abnormalities associated with the HELLP syndrome. A report of three cases.

The "HELLP syndrome" refers to the occurrence of thrombocytopenia, elevated liver enzymes and, at times, hemolysis in patients with preeclampsia. Although uncontrolled series have reported a reversal of thrombocytopenia and elevated liver enzymes with aspirin and colloid infusion, most authors recommend that delivery be done soon after the diagnosis is made. The abnormal laboratory parameters of the HELLP syndrome may be reversed completely with bed rest alone, and with preterm gestations, conservative management may be possible.

Adult↗

Propionyl-coenzyme A carboxylase of Mycobacterium smegmatis. An electron microscopic study.

Propionyl-CoA carboxylase has been purified to homogeneity and examined in electron microscope. The native carboxylase presents a profile with a large central subunit to which smaller subunits are attached. The central subunit has two prominent profiles, one circular (100 A) with a central hole and the other rectangular (70 X 100 A). The six polypeptides of this subunit appear to be arranged in a cylindrical structure. Six spherical (50 A) biotin-containing peripheral subunits are attached in sets of three to the two opposite circular faces of the central subunit. A model of the 18-S carboxylase is presented.

Carboxy-Lyases↗

Metabolic alterations in trauma: lactate and pyruvate levels after aortic surgery.

Arterial lactate and pyruvate concentrations were measured in five patients undergoing abdominal aneurysmectomy. In all cases, a bimodal rise and fall in both lactate and pyruvate levels were observed. Hemodynamic data indicated that cardiac output as well as oxygen delivery and consumption were constant throughout this period. The first lactate peak which was initially related to the cross-clamping of the aorta, but which continued for a period of 5 h after removal of the clamp, was characterized by elevated lactate to pyruvate ratios indicating an anaerobiosis. A transient hyperglycemia was also present during this lactate peak. Ten to 15 h later, when lactate and pyruvate levels were returning to normal levels, a second peak occurred in both lactate and pyruvate lasting 10 h in all five patients. A relatively large increase in pyruvate levels also occurred during this second peak so that the lactate to pyruvate ratios remained normal. This suggests that the second peak was characterized by aerobic metabolism and may have been due to a defect in pyruvate metabolism.

Aorta, Abdominal↗

Purification and subunit structure of propionyl coenzyme A carboxylase of Mycobacterium smegmatis.

Propionyl-CoA carboxylase (EC 6.4.1.3) has been purified from Mycobacterium smegmatis. It has a molecular weight of about 500,000. On sodium dodecyl sulfate gels it dissociates into two subunits with molecular weights of 64,000 and 57,000. There are 3.8 mol of biotin/500,000 g of protein. The biotin is associated entirely with the heavier subunit. The enzyme also used acetyl-CoA as a substrate. No other acetyl-CoA carboxylase could be detected in this organism.

Acyl Coenzyme A↗

The binding of ribosomal protein S4 does not change the gross conformation of the 16 S RNA.

The binding of ribosomal protein S4 to the 16 S RNA does not result in a large shape or conformational change in the 16 S RNA under the conditions of reconstitution. The sedimentation coefficient, frictional coefficient ratio, and effective hydrodynamic radius of the 16 S RNA.protein S4 complex are very similar to those obtained for the 16 S RNA free in solution. Only subtle conformational differences were obtained in the comparison of the complex and free 16 S RNA by circular dichroism. Thus, extensive organization of the 16 S RNA by ribosomal protein S4 is not a step in the process of self-assembly of the 30 S subunit.

Circular Dichroism↗