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Biomedical subjects

R H Kelly

Publications and source records attributed to R H Kelly.

11 recordsLinked to original sources

Lack of increase in heterozygous alpha 1-antitrypsin deficiency phenotypes among patients with hepatocellular and bile duct carcinoma.

Homozygous alpha 1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous alpha 1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous alpha 1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers. We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. alpha 1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and chi 2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous alpha 1-antitrypsin deficiency. Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus-related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct

Beta 2 transferrin application in otology.

The diagnosis and management of perilymphatic fistula has received considerable attention in recent years. Despite the use of sophisticated technology, the diagnosis of perilymphatic fistula continues to rest primarily upon clinical suspicion and the exclusion of other disorders. In addition, the confirmation of a perilymphatic fistula during surgical exploration is usually based upon the subjective observation of fluid pooling in niches of the middle ear. A sensitive and objective laboratory test for identifying perilymph in the middle ear would be a useful adjunct for the diagnosis and management of perilymphatic fistula. The objective of this paper is to demonstrate the potential utility of beta 2 (beta 2) transferrin assay in the diagnosis of perilymphatic fistula. To accomplish this objective, we confirmed that beta 2 transferrin is present in living human perilymph and is absent in the normal or inflamed middle ear. In addition, the utility of beta 2 transferrin assay in the diagnosis of cerebrospinal fluid otorrhea is presented.

Aged

Lymphocyte migratory pathways in adjuvant disease. II. Distribution of thoracic duct lymph-borne immunoblasts.

Evidence for enhanced extravasation of thoracic duct lymph-borne immuno-blasts within joints of rats during the onset of adjuvant disease was sought by adoptive transfer of cells radiolabeled with (125I)-iodo-2-deoxyuridine. Migratory behavior of cells from normal or adjuvant disease donors, during both inductive and overt stages of the disease process, was contrasted in normal and adjuvant disease recipients. The results provided no evidence to indicate enhanced joint-seeking properties of lymph-borne immuno-blasts obtained from adjuvant disease donors, either during the period preceding overt joint involvement or during the phase of chronic inflammation. The ability of lymph-borne cells to passively transfer the disease thus appears more likely due to systemic actions of these cells, mediators produced by them, or concomitantly passaged antigen upon patterns of inflammatory cell mobilization and/or vascular endothelial cell activation.

Animals

Acute hemorrhagic pancreatic necrosis in mice: lack of a pathogenetic role for complement.

Feeding a choline-deficient diet containing 0.5% DL-ethionine induces an acute hemorrhagic pancreatitis in 100% of young female mice. Evidence for deposition of the third component of complement (C3) on acinar cell plasma membranes was sought, during the inductive stages, by a sandwich immunofluorescence technique. Such a localization could not be demonstrated even though the method is capable of detecting less than 8 x 10(-5) microgram of protein/mm2 of cell membrane. Artifactual binding of immunoglobulin reagents was encountered when goat antisera, with high levels of circulating immune complexes, formed the middle layer in the sandwich technique. This was attributed to the appearance of Fc receptors on the plasma membrane of degenerating acinar cells, and could be avoided by ultracentrifuging acinar cells, and could be avoided by ultracentrifuging the goat antisera prior to sue. In view of the fact that C3 cleavage represents an amplification loop in both the calssical and alternate pathways of complement activation, the lack of demonstrable C3 staining in tbe present experiments strongly suggests that complement plays no role in acinar cell necrosis in this model of pancreatitis.

Acute Disease

Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells.

In the rabbit a number of large mononuclear cells with ruffled surface membranes travel from the skin and superficial tissues of the leg, via the lymphatics, to the popliteal lymph node: they constitute 40-50% of the total cell population in the afferent lymph. About 10% of these cells are actively phagocytic when tested in vitro and about 3% are found to contain Langerhans granules. After isotopic labelling the majority of lymph-borne mononuclear cells can be detected within the regional node for at least 24 hours; most being located in the paracortex and a few in the interfollicular cortex. It is proposed that these cells, including those containing Langerhans granules, belong to the "mononuclear phagocyte system." Possible functions of these lymph-borne cells are discussed with particular reference to antigen transport.

Adenosine

Lymphocyte migratory pathways in adjuvant disease. I. Distribution of 51Cr-labeled thoracic duct lymph-borne.

Evidence for selective extravasation of thoracic duct lymph-borne cells, derived from rats with adjuvant disease, within joints of normal or adjuvant arthritic recipients was sough by adoptive transfer of radiolabeled cells. Control studies were carried out in parallel using thoracic ducts cells from normal donors. No increased homing of lymph-borne cells to inflamed portions of the limbs was detected when cells from adjuvant arthritic donors were compared with those of normal controls. Inflammatory changes, ie, adjuvant-induced disease, in the recipient produced a significant nonspecific enhancement of extravasation; cells from normal and adjuvant arthritic donors responded equally well. One difference in migratory behavior between lymph-borne cells from adjuvant arthritic and normal animals was the increased ability of the former to localize within certain lymph nodes. A possible association between this traffic and the development of chronic inflammatory processes within joints is discussed.

Animals

A comparison of the hematogenous cell infiltrate evoked by lymphokine injection with that of delayed hypersensitivity reactions.

Lymphokine preparations of high potency obtained by in vitro assay were employed in vivo to determine whether they could produce inflammatory responses showing a cellular infiltrate that qualitatively or quantitatively resembled responses of delayed hypersensitivity. Hematogenous cell infiltrates in guinea pig skin were characterized in terms of the number and types of participating cells following intradermal injection of either lymphokines or an antigen (PPD) to which the animals exhibited delayed hypersensitivity. The dose of lymphokine or PPD per skin test site was selected on the basis of comparable ability to enhance vascular permeability. Delayed hypersensitivity responses showed, as expected, a persistent mononuclear cell exudate both in dermis and subcutis, but most notable in the dermis, during the 24 hours following antigen injection. In contrast, the response to lymphokine over the same period was characteristically neutrophilic and principally in the subcutis. There was no pronounced mononuclear cell infiltrate at any time throughout the reaction to lymphokine. It is concluded that preformed lymphokine produces a pattern of increased vascular permeability appropriate to a mediator of delayed hypersensitivity reactions, provided there is sustained secretion of this material. The ability of lymphokine to cause carbon labeling of dermal capillaries is also pertinent to a mediator of delayed hypersensitivity. The absence of significant mononuclear cell accumulation suggests that the in vitro chemotactic activity of lymphokine toward mononuclear cells may be more important for retention of mononuclear cells in the extravascular connective tissue space than for their selective accumulation.

Animals

Functional anatomy of lymph nodes. I. The paracortical cords.

Histological alterations in the paracortical zones of rabbit lymph nodes were produced by the intravenous injection of the acridine dye euchrysin. The paracortical parenchyma was reduced to narrow bands of lymphoid tissue which cuffed and outlined the venules against a distended and cell-filled sinus system. These perivenous lymphocyte cuffs, termed the paracortical cords, represented the basic anatomical unit of the thymus-dependent paracortical area. Both the paracortical cords and sinuses are cell traffic pathways, but during stages of antigen-induced lymphocyte trapping the cords retain more cells than do the sinuses. Proliferation of T cells and differentiation of B cells both occur within these cords in a microenvironment conductive to cellular cooperation.

Acridines

Accelerated cytodifferentiation of antibody-secreting cells in guinea-pig lymph nodes stimulated by sheep erythrocytes and lymphokines.

Lymphokines, produced in response to structurally unrelated antigens, altered the course of a primary anti-sheep erythrocyte plaque-forming cell response within the regional lymph nodes of normal guinea-pigs. Intralymphatic injection of a small dose of lymphokines (0-5-8 mug) 1 day after antigen priming accelerated the rate of indirect plaque-forming cell cytodifferentiation between the 5th and the 9th days of the response. This effect was not related to changes in the level of antigen trapping by lymph node macrophages, but the lymphocyte mitogenic activity may have been important for the response since there was a significant increase in [3H]thymidine incorporation within the lymphokine-treated nodes on the 3rd day following immunization.

Animals