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Biomedical subjects

K B Bacon

Publications and source records attributed to K B Bacon.

67 records · Page 4Linked to original sources
PubMed1990

Lipid lymphocyte chemoattractants in psoriasis.

In view of the evidence that lymphocyte infiltrates are a constant feature of the skin lesions of psoriasis and the demonstration that certain hydroxylated metabolites of arachidonic acid are present in lesional psoriatic skin and possess lymphocyte chemoattractant properties, lipid extracts of samples from lesional and normal skin were assayed to determine which are the predominant lipid lymphocyte chemoattractants in psoriasis. Dilution-related lymphocyte chemoattractant activity was found in lipid extracts of stratum corneum samples from psoriatic lesions, but not in similar extracts of stratum corneum from the heels of normal volunteers, whereas aqueous extracts of the samples from both sources contained equivalent amounts of this activity. Subsequent purification of lesional stratum corneum lipid extracts by straight and reversed phase high performance liquid chromatography (HPLC) revealed the presence of at least two different lipid chemoattractants, one major component being identified as 12-(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12[R]-HETE) by its biological and chromatographic properties. These compounds may play a role in the pathogenesis of the lymphocyte infiltrates in psoriatic lesions.

Adult↗
PubMed1990

Lymphocyte chemoattractants in psoriasis and normal skin.

The local production of lymphocyte attractants may influence both physiologic lymphocyte trafficking in the skin as well as the infiltration of these cells in pathologic states. Recent evidence for the production of acidic lipid lymphocyte chemoattractants, particularly 12[R]-hydroxyeicosatetraenoic acid, in psoriatic lesions is reviewed. Water extractable lymphocyte attractant activity may also be recovered from both normal skin samples and psoriatic lesional stratum corneum, and may be important in the pathophysiology of lymphocyte trafficking. Less than 10 kD activity from normal skin has undergone the most detailed characterization. This has led to the isolation of a novel, as yet unidentified compound from normal skin, which we have termed "plasma-associated lymphocyte chemoattractant" (PALC).

Cell Movement↗
PubMed1990

Leukocyte chemoattractant cytokines of the epidermis.

The constitutive production of interleukin-1 alpha-like material in normal human epidermis, its inflammatory properties, and the mechanism of its inflammatory action are briefly reviewed. The isolation of interleukin-8 from psoriatic lesions, its in vitro production, and leukocyte chemoattractant properties are also described. Available evidence suggests that interleukins-1 and -8 are inflammatory cytokines of major potential importance in the induction of leukocyte infiltrates in human skin.

Chemotactic Factors↗
PubMed1990

Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides.

The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and gamma interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides.

Adult↗
PubMed1990

Potent and selective inhibition of in vitro lymphocyte migration by cyclosporine and dexamethasone.

We have studied the in vitro effects of cyclosporine A (CsA) and dexamethasone on lymphocyte migration, which is considered to play an important role in the pathogenesis of inflammatory and auto-immune disorders. Using a 48-well microchemotaxis assay, dose-related migratory responses of mixed peripheral blood lymphocytes (PBL) to recombinant interleukin (rIL)-1 alpha, rIL-2, leukotriene B4 (LTB4) and zymosan activated plasma (ZAP) were demonstrated. When preincubated with PBL under plasma free conditions and in the presence of undiluted autologous plasma, CsA in the dose range 4 x 10(-13)-1.6 x 10(-7) M caused concentration related inhibition of lymphocyte migration in response to fixed concentrations of rIL-1 alpha and rIL-2. CsA in the same dose range had no effect on the migration of PBL in response to ZAP and LTB4. Under plasma-free conditions dexamethasone (1 x 10(-11)-4 x 10(-6) M) caused concentration related inhibition of PBL migration in response to rIL-1 alpha and LTB4, but had no effect on the responses to rIL-2 and ZAP. These data provide evidence that CsA and dexamethasone are potent and selective inhibitors of in vitro lymphocyte migration, effects which may contribute to their therapeutic efficacy in vivo.

Chemotaxis, Leukocyte↗
PubMed1989

Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists.

The role of calcium in interleukin- (IL) 8-, IL-1 alpha- and IL-1 beta-induced lymphocyte migration has been investigated by using the calcium channel antagonists, verapamil, nifedipine, diltiazem (IL-8) and the optical isomers of the dihydropyridine analogue SDZ 202-791 (IL-8, IL-1 alpha and IL-1 beta). Potent inhibition of IL-8-induced migration was observed in response to nifedipine (IC50 = 10 nM), verapamil (IC50 = 60 nM) and diltiazem (IC50 = 10 nM). The (+)-isomer of SDZ 202-791 was without effect on any of the agonists tested, however, the (-)-isomer induced dose-related inhibition of stimulated migration, IC50 values being 0.1 nM, 10 pM and 1.0 nM, for IL-8-, IL-1 alpha- and IL-1 beta-induced migration, respectively. Reversal of the inhibitory effects of the (-)-isomer was obtained in the presence of increasing concentrations of (+)-isomer. The induction of lymphocyte migration by IL-8, IL-1 alpha and IL-1 beta therefore appears to be a process dependent on calcium channel activation.

Calcium Channel Blockers↗
PubMed1989

Screening and selection process for studies of menstrually-related changes.

The screening process of women who volunteered to participate in "studies of the menstrual cycle" is described. It is demonstrated that in order to arrive at a desired number of subjects who meet criteria for premenstrual changes and are in a good physical and mental status, one should recruit an extremely large number of candidates to start with. The yield of each screening procedure is presented. It is clear that fulfillment of inclusion and exclusion criteria can be obtained by a phone interview while important criteria can be clarified only by prospective monitoring of symptoms and personal structured interviews. Methods and procedures that can improve yield and decrease effort in recruitment are suggested.

Advertising↗
PubMed1989

The normalcy of self-proclaimed "normal volunteers".

Volunteers who claimed they were "healthy and normal" and did not reveal any physical or mental abnormality or medication use during brief structured interviews underwent detailed structured interviews with the Schedule for Affective Disorders and Schizophrenia. Diagnoses were based on the Research Diagnostic Criteria (RDC), and family history was determined with the Family History RDC. Of the 121 volunteers, 16.5% met criteria for diagnoses of current mental disorders. Of the 104 without current DSM-III axis I diagnoses, 35.6% had past histories and 39.4% had family histories of mental illness. These results emphasize the need for thorough assessment of "normal volunteers."

Adolescent↗
PubMed1988

Organ selective conversion of prostaglandin D2 to 9 alpha, 11 beta-prostaglandin F2 and its subsequent metabolism in rat, rabbit and guinea pig.

Cell-free 100,000 g supernatants from liver, kidney, lung and caecum of rat, rabbit and guinea-pig were compared for their ability to transform prostaglandins F2 alpha, D2, E2 and 9 alpha, 11 beta-prostaglandin F2 (11epi-PGF 2 alpha) to metabolic products. Experiments utilized multitritiated substrate PGs, with assessment of biotransformation by TLC, HPLC and GC/MS. PGF2 alpha was converted via the sulphasalazine analogue-inhibitable NAD+-dependent 15-hydroxy-prostaglandin dehydrogenase pathway (15-PGDH), with high activity (greater than 5 pmol/min/mg protein) in all 12 systems except rat and rabbit liver (e.g. guinea-pig kidney and rat caecum both 64 pmol/min/mg; rat liver 0.3 pmol/min/mg), forming 15-keto and 13,14-dihydro-15-keto metabolites as determined by TLC, HPLC and GC/MS. Prostaglandin D2 was not transformed in similar fashion in NAD+- or NADP+-supplemented incubations in any of the 12 cytosolic systems. However, PGD2 was converted to a single product identified by TLC, HPLC and GC/MS as 9 alpha, 11 beta-PGF2 in certain of the systems when supplemented with an NADPH regenerating system, with high activity in guinea-pig kidney (55.0 pmol/min/mg), guinea-pig liver (27.5 pmol/min/mg) and rabbit liver (13.7 pmol/min/mg) and less than 5 pmol/min/mg in 8 of the remaining 9 systems. This stereospecific 11-ketoreductase of rabbit and guinea-pig liver was stable to 10 min heating at 50 degrees, dialysis, storage at -20 degrees and repeated freeze/thawing but was not inhibited by sulphasalazine analogues. The 11-ketoreductase had a markedly different tissue profile from PGE2 9-ketoreductase, which was shown to convert PGE2 stereospecifically to 9 alpha, 11 alpha-prostaglandin F2 (PGF2 alpha) and was present at highest activity in rabbit liver and kidney. Evidence was obtained that 9 alpha, 11 beta-PGF2 was actively transformed by the sulphasalazine-inhitable 15-PGDH pathway at approximately one third of the rate of PGF2 alpha with high activity in several cytosolic systems (e.g. rat caecum, guinea-pig liver and kidney), suggesting that further transformation in vivo of this biologically active product of PGD2 metabolism could be initiated by this route.

Animals↗
PubMed1988

Contrasting in vitro lymphocyte chemotactic activity of the hydroxyl enantiomers of 12-hydroxy-5,8,10,14-eicosatetraenoic acid.

1. The chemotactic activity of 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE), 12(S)-HETE and leukotriene B4 (LTB4) for human mixed peripheral blood lymphocytes has been assessed in a 48-well microchemotaxis assay. Responses to the standard lymphocyte chemoattractants, zymosan-activated plasma, casein and N-formyl-methionyl-leucyl-phenylalanine (fMLP) were also measured. 2. 12(R)-HETE was shown to be chemotactic for lymphocytes over the range 5 x 10(-7) to 5 x 10(-5) M. In contrast, negligible chemotactic responses to 12(S)-HETE were obtained. 3. LTB4 was 200 times more potent than 12(R)-HETE as a lymphocyte chemoattractant, although maximal responses to the two agonists were similar. 4. 12(R)-HETE and LTB4, which are present in extracts of samples from the skin lesions of psoriasis, may be, at least in part, responsible for the lymphocyte infiltrate which is a characteristic feature of this disease.

Cell Movement↗