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Biomedical subjects

J B Hay

Publications and source records attributed to J B Hay.

At least 91 records · Page 5Linked to original sources

Changes in mixed lymphocyte culture-reactive lymphocytes following alloimmunization of single lymph nodes in sheep.

When an "isolated" single lymph node is challenged with irradiated allogeneic lymphocytes, there is a change in the reactivity of the lymphocytes flowing out of the node when they are cultured in vitro in unidirectional mixed lymphocyte cultures (MLC) against the immunizing lymphocytes. These changes in the reactivity of the recipient lymphocytes are shortlived, follow a set time sequence in relation to the cell traffic changes accompanying the immune response, are the property of small lymphocytes and not blast cells, are exhibited by surface Ig-negative cells, and they are specific for the donor lymphocytes. It is suggested that antigen causes the selective retention of antigen-specific lymphocytes within the stimulated node followed by the proliferation and differentiation of large numbers of antigen-specific cells, which then leave the lymph node as small lymphocytes.

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Kinetics of prostaglandin production in various inflammatory lesions, measured in draining lymph.

Efferent lymph was collected over long periods via catheters surgically placed in popliteal and prefemoral lymph nodes of sheep. Prostaglandin (PG) E and F equivalents were measured with a radioimmunoassay. After stimulation with heat-killed Escherichia coli, PG levels rose dramatically in the efferent lymph but were undetectable in the contralateral control lymphatics or in the systemic circulation. When E coli were infused directly into a lymph node, the PG levels in the effluent lymph were inhibited with indomethacin. Carrageenan, delayed hypersensitivity, and lymphocyte transfer reactions were also studied. In the classic acute inflammations (caused by E coli and carrageenan) the PG levels rose early in the response (first 4 to 6 hours) compared with delayed production in the immune reactions. With PPD, PG levels peaked between 10 and 20 hours after injections, while PG rose 127 hours after allogeneic lymphocytes were injected. These results are discussed in relation to the role of PG in inflammation, and the use of the sheep lymphatic model in PG research is emphasized.

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Distribution of androgen metabolizing enzymes in isolated tissues of human forehead and axillary skin.

The distribution of androgen metabolism in human skin was studied using tissues isolated either by direct dissection of axillary skin or by dissection of collagenase-digested forehead and axillary skin. All tissues (epidermis, sweat glands, sebaceous glands, hair follicles and dermis) were found to contain 17beta-, 3beta- and 3alpha-hydroxysteroid dehydrogenase (HSD) activities, 3beta-hydroxysteroid dehydrogenase-delta4--5 isomerase (delta5-3beta-HSD) activity and 5alpha-reductase activity. All tissues converted testosterone into 5alpha-dihydrotestosterone. In confirmation of previous histochemical studies, over 90% of the delta5-3beta-HSD of forehead skin was found in the sebaceous glands. In forehead skin, 40--66% of the 5alpha-reductase activity was in the sebaceous glands, while in axillary skin 50--70% was in the sweat glands, especially the apocrine glands. There was a more even distribution of 17beta-HSD activity in skin tissues than histochemical studies have indicated previously. Knowledge of the distribution of these enzymes has helped in the understanding of the function of androgen metabolism in skin.

Adult↗

Blood flow in rabbit eyes after keratectomy and corneal transplantation.

We used radio-labelled microspheres to study the distribution of blood flow in different regions of rabbit eyes with inflamed corneas resulting from trauma or allograft reaction. The blood flow in the cornea, the anterior uvea and the regional lymph nodes draining it was increased, but total flow in the eye did not increase. More blood went to the anterior uvea at the expense of the rest of the eye. Blood flow at the limbus was higher in the inflamed corneas than in the controls.

Animals↗

The flow of blood to lymph nodes and its relation to lymphocyte traffic and the immune response.

The blood flow to individual lymph nodes of sheep and rabbits has been determined with 85Sr-labeled microspheres. A popliteal node of the sheep received 0.014% of the cardiac output and a comparable node in the rabbit 0.011%. A sheep lymph node weighing 1 g received an average of 24 ml/h of blood. It was calculated that there was a highly selective removal of lymphocytes by the node and that an equivalent to one in every four lymphocytes that entered a normal lymph node migrated out of the blood, through the substance of the node, and into the efferent lymph. During the immune response to either allogeneic lymphocytes or tuberculin, the blood flow to sheep lymph nodes, even without considering the increase in node weight, increased an average of fourfold. During the primary immune response in the rabbit to keyhole limpet hemocyanin, the blood flow increased threefold. The increase in blood flow preceded the antigen-induced increase in lymphocyte traffic recorded in the efferent lymph. The early phase of increased blood flow was considered to be due to hyperemia, whereas the latter phase had a significant angiogenesis component. It was calculated that an equivalent to 60% of the entire mobilizable pool of lymphocytes could pass through an average lymph node in the blood during an immune response lasting 5 days.

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A study of the in vitro metabolism of androgens by human scalp and pubic skin.

The metabolism of dehydroepiandrosterone, androstenedione and testosterone was compared in vitro in human scalp, forehead, pubic and axillary skin biopsies. Conversion of testosterone to the metabolite 5alpha-dihydrotestosterone, believed to be the active form of androgen, occurred in all tissues; however 17-oxosteroids such as androstenedione, 5alpha-androstanedione and androsterone were also formed from testosterone and were the major metabolites of scalp and forehead skin. While 17beta-hydroxy steroid dehydrogenase activity was present in every skin sample, it was evident there were differences in the direction of operation of this enzyme in skin from different body sites. Axillary skin readily metabolised androstenedione and dehydroepiandrosterone to active 17beta-hydroxy steroids such as testosterone and 5alpha-dihydrotestosterone, but these compounds were minor metabolites of androstenedione and dehydroepiandrosterone in forehead and scalp skin despite their activity in 17beta-oxidation of testosterone. Pubic skin was intermediate between axillary and scalp skin in its ability to form 17beta-hydroxy products from androstenedione and dehydroepiandrosterone. It is suggested these patterns of metabolism may reflect differences in androgen sensitivity.

Adult↗

The role of hyperemia in cellular hypersensitivity reactions.

The three physiological processes vascular permeability, blood flow and lymphocyte migration were all enhanced in tuberculin reactions induced in guinea pigs and sheep and also in normal lymphocyte transfer reactions in sheep. Microspheres labelled with 85Sr were used to measure blood flow to dermal sites and it was found that cellular hypersensitivity reactions had blood flows 7-25 times that of normal skin at the reaction peak. Vascular permeability was measured as an increase in the flow rate of afferent lymph or, in guinea pigs, as the enhanced leakage of intravascular 125I-albumin. When the permeability-inducing peptide bradykinin was injected directly into tuberculin reaction, the resulting permeability was greater than the sum of the tuberculin and bradykinin permeability taken individually and it was concluded that the hyperemia enhanced the permeability-inducing capacity of bradykinin. When the traffic of lymphocytes through hypersensitivity lesions was measured in sheep by cannulating the regional afferent lymph vessels and continuously collecting the lymph, the increase in lymphocyte traffic was of the same order of magnitude as the increase in blood flow. It is suggested than the antigen-induced enhancement of blood flow caused the increase in lymphocyte traffic and that the mechanism was similar to that occurring within lymph nodes during the immune response to all antigens.

Animals↗

Comparison of the blood supply to diethylnitrosamine-induced hyperplastic nodules and hepatomas and to the surrounding liver.

Intravascular injection of radionuclide-labeled microspheres was used to compare the blood supply to diethylnitrosamine-induced hyperplastic liver nodules and hepatomas with the blood supply to the surrounding, histologically normal liver. Microspheres injected into the heart or portal vein lodged in the organs of control and diethylnitrosamine-treated rats providing a quantitative index of blood supply to the microvascular bed. The blood supply is expressed as percentage of cardiac output (arterial) or cpm (portal) per organ, lobe, g tissue, etc. The fraction of the cardiac output received by lung, kidneys, spleen, and liver was similar in control and carcinogen-treated animals. The arterial blood supply of 23 nodules and hepatomas was variable [1.17 +/- 0.22% (S.E.) cardiac output per g, fixed weight], but it was similar to the arterial supply to the surrounding tissue (1.12 +/- 0.21% cardiac output per g, fixed weight). In contrast the portal blood supply to 25 selected lesions wa 39 +/- 6% that of the surrounding liver tissue. There was no apparent relationship between blood supply and lesion size or histological appearance. While only 0.13 +/- 0.04% of the microspheres injected via the portal system were recovered in the lungs of control rats, approximately 100 times this number bypassed or escaped the liver containing nodules and hepatomas and lodged in the lungs. Such alterations in blood flow could contribute to biological diversification of hepatic lesions in successive stages of cancer evolution and could facilitate metastasis from the liver.

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Studies on the glycolipids of sheep thymus and of normal and concanavalin A-stimulated sheep peripheral lymphocytes.

The neutral glycolipids and gangliosides of sheep thymus and of sheep peripheral lymphocytes were compared. The patterns of both of these major classes of glycolipids were more complex in thymus than in the lymphocytes. The incorporation of radioactivity from D-[1-14C]galactose into the individual glycolipids of control and concanavalin A-stimulated sheep peripheral lymphocytes was also studied. A marked enhancement of incorporation into trihexosylceramide and an alteration of the pattern of incorporation into gangliosides were noted in the mitogen-treated cells. The results suggest that significant alterations of glycolipid composition and metabolism may occur during at least certain stages of lymphocyte differentiation.

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The modulation of enhanced vascular permeability by prostaglandins through alterations in blood flow (hyperemia).

The enhanced vascular permeability induced by histamine or bradykinin in the skin of the guinea-pig and rabbit was significantly augmented by small amounts of prostaglandins of the E type. When injected alone these prostaglandins had little effect on vascular permeability. Furthermore, E type prostaglandins were found to be more potent at inducing hyperemia than either histamine or bradykinin. Prostaglandin F2alpha did not enhance the vascular permeability induced by histamine or bradykinin nor did it produce hyperemia in the skin. In the rat, prostaglandins alone enhanced vascular permeability but they also increased the effect of histamine, serotonin and bradykinin. Using 85Sr-microspheres to measure blood flow a correlation was found between the degree of hyperemia produced by prostaglandins and the degree to which they augmented enhanced vascular permeability due to histamine, serotonin or bradykinin. Prostaglandins therefore can directly mimic the hyperemia of the inflammatory process and can also modulate the changes in vascular permeability caused by other mediators of inflammation.

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