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Biomedical subjects

W Moore

Publications and source records attributed to W Moore.

At least 73 records · Page 4Linked to original sources

Clonal growth of immunocytochemically identified islet beta and alpha cells in culture.

The proliferative capacity of individual immunocytochemically identified islet beta cells was investigated in tissue culture. The pancreatic digest was filtered through a 20-micron filter to eliminate partially digested tissue fragments and islets; it was then cultured at low density to allow assessment of single cells. The type of cell was identified immunocytochemically by reaction with antibody to insulin or glucagon, and DNA synthesis was estimated from autoradiographs after incorporation of tritiated thymidine. Single immunocytochemically reactive beta or alpha cells attached to the culture substratum and then proliferated, directly proportional to time in culture. Single beta cells did not incorporate thymidine after 1 day in culture; nonendocrine cells, presumed to be mainly fibroblasts, readily incorporated thymidine. Beyond the first day, about 10% of the beta cells incorporated thymidine. The number of radioactively labeled, immunocytochemically reactive beta cells increased for 5 days in culture and then remained at the elevated level until experiments were terminated at 12 days. DNA synthesis in beta cells occurred in two waves separated by about 3 days, suggesting a generation time of about 3 days for immunocytochemically identified beta cells. Fetal calf serum was found to be an essential culture medium ingredient to sustain thymidine incorporation; horse serum was found to be an unsuitable substitute. Mitotic figures were recorded in differentiated beta and alpha cells. These studies conclusively show that differentiated beta and alpha cells can proliferate in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of a totally implantable access device for chemotherapy (Port-A-Cath) and long-term percutaneous catheterization (Broviac).

Because of the difficulty in maintaining vascular access in patients receiving aggressive parenteral chemotherapy, a growing number of patients have had implantation of either percutaneous or subcutaneous devices allowing permanent intravenous access. In our study, between July 1980 and July 1985, 110 patients had placement of a Broviac catheter, while 100 patients had placement of a subcutaneous device via a subclavian venous approach. Both groups of patients were identical regarding age, primary malignancy, chemotherapy, and nutritional status. Catheter-related sepsis occurred in 15% and thrombotic occlusion in 22% of those patients with Broviac catheters, compared with 3% and 1%, respectively, in patients having subcutaneous reservoirs. Although the initial cost of the subcutaneous reservoir is greater, overall cost of maintenance of the percutaneous catheter far exceeds that of the reservoir because of the need for daily catheter care and heparin flushing of the Broviac device, which is unnecessary for the subcutaneous port. Our experience favors the use of the subcutaneous reservoir in patients receiving prolonged chemotherapy.

Antineoplastic Agents

Inactivation of gamma-glutamylcysteine synthetase, but not of glutamine synthetase, by S-sulfocysteine and S-sulfohomocysteine.

The reactions catalyzed by gamma-glutamylcysteine synthetase and glutamine synthetase are thought to proceed via enzyme-bound gamma-glutamyl phosphate intermediates. We investigated the possibility that S-sulfocysteine and S-sulfohomocysteine might act as analogs of gamma-glutamyl phosphate or of the associated putative tetrahedral intermediates. The D- and L-enantiomers of S-sulfocysteine and S-sulfohomocysteine were found to rapidly inactivate rat kidney gamma-glutamylcysteine synthetase but to be reversible inhibitors of sheep brain glutamine synthetase. Inactivation of gamma-glutamylcysteine synthetase does not require ATP and is associated with noncovalent binding of close to 1 mol of inactivator/mol of enzyme. The findings indicate that the S-sulfo amino acids are transition-state analogs, and that binding of S-sulfo amino acid to the enzyme induces formation of a very stable enzyme-inactivator complex. The data suggest that stabilization of the enzyme-inactivator complex results from interactions involving the sulfenyl sulfur atom of the S-sulfo amino acid and the active site thiol group of the enzyme.

Animals

Interval gangrene occurring after successful lower-extremity revascularization.

Four patients experienced a rare but devastating complication of peripheral vascular reconstructive surgery in which gangrene occurred in the presence of a functioning graft and palpable pulse. Three patients underwent bypass procedure for limb-threatening ischemia. Despite a "satisfactory" postoperative result of a well-perfused distal extremity and strongly palpable pulse, each of these patients developed progressive ischemic gangrene in an area proximal to the distal anastomosis and eventually required amputation. These patients demonstrate the importance for maintaining collaterals to perfuse bypassed segments of the lower extremities. In a patient with inadequate collateral circulation or in whom the profunda perigeniculate collateral pathway has been disrupted or is absent due to disease, it is necessary to revascularize sequential vascular beds.

Aged

Islet neoformation in tissue culture.

We have devised a tissue culture system that permits de novo formation of islets. Neonatal rat pancreata are enzymatically dissociated into single cells. The cell suspension is filtered through polyester cloth with 20 microns pores to exclude cell aggregates as well as preformed islets and a single cell suspension is then plated into tissue culture dishes at a density precluding reaggregation. Pancreatic cells proliferate forming numerous colonies of epithelioid cells. After a confluent monolayer, cells proliferate into a third dimension, the space occupied by the culture medium. Third dimensional proliferation occurs from basal monolayers of epithelioid colonies. At about 9 days in culture, numerous hillocks are visible that are spaced at about 1 mm from one another. Islets are observed to bud from the hillock surfaces. In 1 micron-thick sections, secretion granules are detected with the light microscope in some islet cells. With the electron microscope three basic cell types are seen. One peripherally located cell type is sparsely granulated and appears to be a precursor cell. The other peripherally located cell type shows a homogeneous population of secretion granules characteristic of A-cells. The third cell type is found in the interior of islets containing granules characteristic of B-cells. Islet cells, but not hillock cells, react immunocytochemically for insulin and glucagon. The cultures secrete 2 to 10-fold the amounts of glucagon present in fresh medium. It is concluded that differentiation of A- and B-cells occurs in neoformed islets.

Animals

Optimal proximal anastomosis/tunnel for axillofemoral grafts.

The proximal anastomosis of the axillofemoral graft may be optimally placed with standard "cobra-head" technique at an oblique angle to the axillary artery if a subpectoralis minor course of the graft into the anterior-inferior axilla is used. Theoretical advantages of such an anastomosis include improved flow characteristics, decreased tendency to pseudoaneurysm formation, and a decreased tendency to axillary artery thrombosis or brachial artery embolus.

Axillary Artery

Is pain crisis a cause of death in sickle cell disease?

It has been a matter of controversy as to whether patients with sickle cell disease die of crisis or merely in crisis. The authors reviewed the 74 patients with sickle cell disease autopsied at The Johns Hopkins Hospital. From clinical review, there were 20 (27%) who died with pain crisis, 51 (69%) who died without pain crisis, and 3 (4%) for whom documentation was insufficient. On pathology review, death was attributable to infection in 19 (26%), uremia in 9 (12%), sequestration crisis in 9 (12%), necrotic bone marrow emboli in 7 (9%), and miscellaneous causes in 14 (19%); in 16 (22%) patients no cause of death could be identified. Death was explained in 47/51 (92%) patients without pain crisis; but only in 11/20 (55%, P less than 0.01) patients dying in pain crisis. The disproportionately large number of patients dying in pain crisis with an unexplained cause of death suggests that pain crisis may account for the death of some patients with sickle cell disease.

Adolescent

Powassan viral encephalitis: a review and experimental studies in the horse and rabbit.

Powassan virus strain M794, a member of the Flavivirus genus known to infect man and animals in Canada, was inoculated intracerebrally into rabbits and horses. No clinical signs were observed in rabbits, but widespread encephalitis resulted, characterized by lymphoid perivascular cuffing, lymphocytic meningitis, and lymphocytic choroiditis. In horses, eight days after inoculation, prominent neurological signs occurred and lesions were those of non-suppurative encephalomyelitis, neuronal necrosis, and focal parenchymal necrosis. The virus could not be reisolated from the rabbit or horse brains. Pathologic features, useful in separating some of the common North American equine neurological diseases, are discussed.

Animals

Iatrogenic vascular injury during peripheral revascularization.

Iatrogenic vascular injury may occur during peripheral revascularization procedures secondary to the application of vascular occlusive devices. This review summarizes the known mechanical causes of such injury, relates this to clamp design, and suggests methods to minimize such injury by appropriate selection and handling of vascular occlusive clamps.

Animals

Rehabilitation for lower extremity amputation.

The results of rehabilitation for lower-extremity amputation were analyzed to assess the impact of a center that used a coordinated team combined with modern surgical and prosthetic techniques. Data for group 1 patients (amputated between July 1, 1975, and June 30, 1977) demonstrated a healing rate of 63%, a mean rehabilitation time of 128 days, a mean hospitalization time of 68 days, and a rehabilitation rate of 69% for those who could walk prior to amputation. Data for group 2 (amputated between July 1, 1977, and July 30, 1979) demonstrated an amputation healing rate of 97%, an average rehabilitation time of 30.8 days, a mean hospitalization time of 38 days, and a rehabilitation rate of 100% for those patients who could walk before amputation. There was no difference between groups 1 and 2 in surgical mortality; all other variables, however, showed significant improvement for group 2 patients. Comparison within the same institution of the results of rehabilitation for lower-extremity amputation before and after the initiation of a dedicated amputation center clearly demonstrated the superiority of the center concept.

Adult

Assessment of lipopolysaccharide and outer membrane of Bacteroides fragilis by an antibody-inhibition enzyme-linked immunosorbent assay in physiologic fluids and infected animals.

LPS antigen of Bacteroides fragilis (CDC strain 5462) was measured in vitro in physiologic buffer and undilute human sera by using an antibody-inhibition ELISA system. Other studies were performed to assess detection of the outer membrane antigen from this organism. LPS was repetitively detected at 20 to 50 ng/ml dry weight, and outer membranes were detected at 200 ng/ml total protein in physiologic buffers and human membranes were detected at 200 ng/ml total protein in physiologic buffers and human sera. LPS of other type strains was also detected. Prior incubation of the reagent antibody with multiple whole Enterobacteriaceae organisms and Pseudomonas aeruginosa did not alter test results. Bacteremic rats were easily separated into those with B. fragilis (N = 15) and Escherichia coli (N = 14) bacteremias. Sera from rats in which subcutaneous abscesses were produced with 18 strains of Enterobacteriaceae inhibited detection antibody significantly less than did sera from 30 rats in which abscesses were produced with 11 strains of b. fragilis (p less than 0.01). Although values from the group of animals challenged with B. fragilis were significantly different from the group challenged with Enterobacteriaceae, the present results lack significant sensitivity and specificity for clinical application.

Abscess