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Biomedical subjects

R D Lynch

Publications and source records attributed to R D Lynch.

17 recordsLinked to original sources
PubMed1992

Arterial infections due to Listeria monocytogenes: report of four cases and review of world literature.

Early diagnosis and successful antimicrobial therapy have diminished the frequency of embolomycotic aneurysms, but infected aortic and small vessel aneurysms, arteriosclerotic plaques, and prosthetic grafts are becoming more common. A broad spectrum of pathogens, including Staphylococcus, Salmonella, Enterobacteriaceae, Pseudomonas aeruginosa, and some unusual organisms, are associated with this change. We treated four patients (three with abdominal aortic aneurysms and one with a prosthetic graft) with arterial infections caused by Listeria monocytogenes. Only seven other cases have previously been recorded in the world literature. Infection is suspected when a palpable or radiographically defined aneurysm is present with an otherwise obscure febrile illness. In about one-third of patients, blood cultures have yielded the pathogen. Newer imaging techniques have helped confirm the diagnosis. These infections are best managed by surgical resection in combination with long-term, appropriate antimicrobial therapy with ampicillin or sulfonamides. Unlike other adult listerial infection, except endocarditis, in arterial infection, immunosuppression and malignancy are not predisposing factors.

Aged↗
PubMed1992

Structure, function, and regulation of cellular tight junctions.

The tight junction (TJ) is a dynamic structure that is controlled, in part, by the activity of the cytoskeleton. It has become abundantly clear that, in the presence of Ca2+, assembly of the TJ is the result of cellular interactions that trigger a complex cascade of biochemical events that ultimately lead to the formation of an organized network of TJ elements, the composition of which remains unknown. The TJ functions both as a barrier between two fluid compartments and, to a lesser extent, as a fence between apical and basolateral membrane domains. To meet the many physiological and pathological challenges to which epithelia and endothelia are subjected, the TJ must be capable of a rapid and coordinated response, which depends on complex regulatory mechanisms. The precise characterization of the mechanisms involved in the assembly and regulation of the TJ is an area of current active investigation. However, until the biochemical composition of this structure has been defined and its gene identified, the TJ will continue to be an elusive yet tantalizing challenge to the cell biologist.

Animals↗
PubMed1991

Inhibition of adenine nucleotide synthesis: effect on tight junction structure and function of clone 4 MDCK cells.

The formation and maintenance of tight junctions as a barrier to the diffusion of ions and other water-soluble across epithelia is an energy-dependent process. The administration of N-formyl-hydroxyaminoacetic acid (Hadacidin), an analog of aspartate and a competitive inhibitor of adenylosuccinate synthetase, has been shown to inhibit the multiplication of clone 4 MDCK cells and concomitantly reduce the levels of ATP and cAMP (J. Cell. Physiol. 140, 186-194 (1989)). When added to mitotically quiescent confluent cultures of clone 4 MDCK cells, millimolar concentrations of Hadacidin inhibited the generation of transepithelial electrical resistance (TER). In such cultures passive Na+ permeability was similar to controls indicating that the effect of Hadacidin was not on the transcellular pathway. That these cells were viable was demonstrated by their ability to exclude Trypan Blue, and the fact that they remained competent to develop steady state TER upon removal of the inhibitor. Suppression of TER was completely reversed within 48 h of replacing the Hadacidin-supplemented medium with one containing aspartate. Adenosine, but not aspartate, when added simultaneously with the drug, obviated the latter's effect on TER. A mixture of dibutyryl cAMP (db-cAMP) and theophylline was only partially effective in overcoming the effects of Hadacidin on the development of TER and, in fact, markedly delayed its development in control cultures not treated with the drug. When monolayers with established steady state TER were exposed to Hadacidin, no change was noted during the first 24 h. By 48 h, however, TER had decreased to very low values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1990

Interaction of native and chemically modified albumin with pulmonary microvascular endothelium.

The ability of native and chemically modified bovine serum albumin (BSA) to maintain normal pulmonary microvascular permeability was tested in "bloodless," fluorocarbon emulsion exchange transfused rats. Wet-to-dry weight ratios (W/D) of whole lung and morphometric estimates of the amount of ferritin transported to basement membrane were used to assess changes in water flux and macromolecular transport, respectively. Native and modified BSA in capillary walls were localized by immunogold techniques. Arginine residues of BSA were blocked with cyclohexanedione (CHD-BSA), and lysine residues were modified either by succinylation (Succ-BSA) or reductive methylation. Succinylation and CHD modification of BSA caused alterations in antigenicity and trypsin sensitivity; succinylation reduced the isoelectric point (pI). Whereas administration of either CHD-BSA or Succ-BSA increased the W/D, transport of ferritin to basement membrane was greater in the presence of Succ-BSA than CHD-BSA. By contrast, infusion of reductively methylated BSA in which modified lysines altered neither antigenicity nor pI, resulted in a W/D and amount of ferritin in basement membranes comparable to that of BSA. Binding of CHD-BSA and Succ-BSA to endothelial glycocalyx appeared to be reduced relative to native BSA and reductively methlyated BSA. The lowered pI of Succ-BSA may have contributed to its reduced binding; reductively methylated BSA with an unaltered pI was present in the glycocalyx. These data are consistent with a role for positively charged arginine residues in the interaction of albumin with the glycocalyx. The W/D of animals perfused with BSA was higher than those reported for rats perfused with complete rat serum proteins. This is consistent with the notion that serum factors, in addition to albumin, are required to maintain normal microvascular permeability.

Animals↗
PubMed1989

Reduction of adenine nucleotide content of clone 4 MDCK cells: effects on multiplication, protein synthesis, and morphology.

The antitumor agent hadacidin (N-formyl-hydroxyamino-acetic acid), at 4 mM, inhibited the multiplication of clone 4 Madin Darby canine kidney (MDCK) cells within 24 hr. Growth resumed rapidly upon replacement of hadacidin with aspartate, an observation consistent with the drug's action as a competitive inhibitor of adenylosuccinate synthetase, an enzyme in adenine nucleotide biosynthesis. Data indicate that the drug-treated cells were arrested in S phase of the cell cycle. Accompanying inhibition of multiplication was a 16-fold increase in the area occupied by the cells and a refractoriness to release by treatment with trypsin. None of these changes occurred when 0.5 mM adenosine was included in the incubation mixture containing the inhibitor. Hadacidin decreased the adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) content of the cells as well as the rate at which 3H-leucine was incorporated into protein. In the presence of 1 mM dibutyryl cAMP and theophylline, the drug had no effect on cell division and protein synthesis. The data suggest that, in clone 4 MDCK cells, the effects of hadacidin are mediated by diminishing the level of cAMP.

Adenine Nucleotides↗
PubMed1989

Diagnosis and treatment of pulmonary disorders of patients with the acquired immunodeficiency syndrome (AIDS).

It is apparent that the lung is frequently involved by a number of opportunistic pathogens and neoplasms in AIDS patients. What is even more disconcerting is the fact that often several infections or infection and neoplasm can coexist [236]. At this time, although effective therapy is at hand for most of the disorders mentioned, the patient's underlying immunodeficiency prevents any long-term survival and also usually leads to relapse when treatment is discontinued. Perhaps the use of newer antiviral compounds such as azidothymidine [237] or immunomodulating agents will help to reconstitute the waning immunocompetence and allow more durable responses in these currently fatal complications.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Modulation of tight junction formation in clone 4 MDCK cells by fatty acid supplementation.

Clone 4 MDCK cells, which generate a transepithelial electrical resistance (TER) of greater than 2,000 omega.cm2, were used to examine the role of membrane lipids in the barrier function of tight junctions. Phospholipid acyl groups were modified by supplementing cells grown in serum-free medium with 18:1(n-9), 18:3(n-3), or 18:3(n-6) complexed to albumin. Although both of these polyunsaturated fatty acids depress the melting point of membrane phospholipids, only 18:3(n-6) contributes significantly to eicosanoid production. Saturation indices of the phospholipids of cells supplemented with albumin alone, 18:1(n-9), 18:3(n-3), or 18:3(n-6) were 0.77, 0.78, 1.81, and 1.65, respectively. After trypsinization or removal of Ca2+, cells supplemented with 18:3(n-6) required longer periods of time to reestablish TER than did nonsupplemented cells or those incubated with 18:3(n-3) or 18:1(n-9). In contrast to MDCK strains I and II, clone 4 MDCK cells required continuous protein synthesis not only to reseal preexisting junctions after the addition of Ca2+ to Ca2+-depleted monolayers, but also to maintain steady-state TER. The rate of decay of TER in the presence of 1 microgram/ml of cycloheximide was 1.5 times greater in cells supplemented with either of the two 18:3 isomers than it was in nonsupplemented controls or in cells supplemented with 18:1(n-9). No significant difference was observed in the steady-state TER or selectivity of the tight junctions after fatty acid supplementation. These results suggest that there is a change in the dynamics of junction formation, rather than an alteration in their intrinsic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Inferior vena cava duplication: demonstration by computed tomography.

Two cases demonstrating the computed tomographic (CT) appearance of inferior vena cava (IVC) duplication are presented, and the embryological, clinical, and radiological significance are discussed. Knowledge of caval anomalies can prevent misinterpretation of mediastinal masses, iliac occlusion with venous collaterals, or paravertebral lymph node enlargement. A duplicated IVC can be distinguished from para-aortic lymphadenopathy either by recognition of renal vein drainage or through intravenous contrast enhancement of the venae cavae.

Adult↗
PubMed1977

Decrease in adhesion of cells cultured in polyunsaturated fatty acids.

The addition of long chain unsaturated fatty acids (linoleic, linolenic and arachidonic acids) to BHK cells reduces the cell to substrate adhesion, causes morphological changes and alters the cellular growth properties. The new characteristics are similar to those of transformed cells. The data indicate that the effects are probably due to actual changes in the surface membrane lipids and not due to prostaglandin synthesis.

Arachidonic Acids↗
PubMed1977

Cerebral granulomatous angiitis: case report and literature review.

Granulomatous angiitis is a pathologically distinct central nervous system segmental vasculitis of unknown etiology and pathogenesis which may be indirectly related to herpes zoster infections. The condition primarily affects adults and presents with nonspecific, unexplained progressive neurological dysfunction. The cerebrospinal fluid is often under increased pressure and contains excess protein and white cells, mostly lymphocytes. The necrotizing vasculitis primarily affects the small intracranial arteries and veins and alters vascular permeability, ind,cing cerebral edema. Angiography demonstrates segmental, diffuse, distal vascular irregularity and narrowing, while computed tomography shows poorly defined, diffuse, non-contrast-enhancing low density areas with or without mass effect. In the approprite clinical setting, the angiographic and CT findings should be highly suggestive. The possibility of efficious therapeutic intervention makes early diagnosis important. CT can also be used to monitor therapeutic response.

Aged↗
PubMed1976

Complete retention of phospholipid acyl groups by mammalian cells in culture.

Radiolabeled phosphate, acetate, and glycerol are incorporated into strain L-fibroblast phospholipids. The acetate and glycerol specifically label the fatty acid and glycerol moieties, respectively, of the phospholipids. To study the metabolic fate of the various moieties of phospholipids, cells incubated with the above radiolabeled compounds were transferred to unlabeled medium, and the rate at which phospholipid radioactivity per 10(6) cells decreased was determined. The rate of decrease expected on the basis of cell division alone was estimated either by monitoring increases in cell number, or by measuring the rate at which radiolabeled DNA per 10(6) cells decreased. Both phospholipid phosphorus and glycerol are lost at a rate greater than can be accounted for by cell division alone. By contrast, nearly all phospholipid acyl chains were retained by the cell to the same extent as radiolabeled DNA. While presence of nonradioactive glycerol in the medium increased the rate at which glycerol was lost from phospholipid, the addition of exogenous fatty acid was without effect on the retention of phospholipid acyl groups. The acyl-glycerol bond of phosphatidylcholine is metabolically more labile than that of phosphatidylethanolamine. Together the data suggest that although L-fibroblast phospholipids undergo deacylation-reacylation reactions, the acyl chains do not equilibrate with either extracellular or intracellular pools of unesterified fatty acid.

Acetates↗