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Biomedical subjects

K M Brown

Publications and source records attributed to K M Brown.

At least 73 records · Page 4Linked to original sources
PubMed1994

Superimposing spatially coherent electromagnetic noise inhibits field-induced abnormalities in developing chick embryos.

Living cells exist in an electrically noisy environment. This has led to the so-called "signal-to-noise" problem whereby cells are observed to respond to extremely-low-frequency (ELF) exogenous fields that are several orders of magnitude weaker than local endogenous fields associated with thermal fluctuations. To resolve this dilemma, we propose that living cells are affected only by electromagnetic fields that are spatially coherent over their surface. The basic idea is that a significant number of receptors must be simultaneously and coherently activated (biological cooperativity) to produce effects on the biochemical functioning of the cell. However, like all physical detection systems, cells are subject to the laws of conventional physics and can be confused by noise. This suggests that a spatially coherent but temporally random noise field superimposed on a coherent ELF signal will defeat the mechanism of discrimination against noise, and any observed field-induced bioeffects would be suppressed. An experimental test of this idea was conducted using morphological abnormalities in developing chick embryos caused by electromagnetic field exposure as the endpoint. At an impressed noise amplitude comparable to the ELF field strength (but roughly one-thousandth of the thermal noise field), the increased abnormality rate observed with only the ELF field present was reduced to a level essentially the same as for the control embryos.

Abnormalities, Radiation-Induced↗
PubMed1994

Vitamin E supplementation suppresses indexes of lipid peroxidation and platelet counts in blood of smokers and nonsmokers but plasma lipoprotein concentrations remain unchanged.

Smokers incur a sustained free radical load that may increase their vitamin E requirement. Erythrocytes of male smokers from a Scottish population with a habitually low vitamin E intake were more susceptible to hydrogen peroxide-stimulated peroxidation than were those from nonsmokers (P < 0.001). Plasma concentrations of lipid peroxides, thiobarbituric acid reactive substances, and conjugated dienes were also elevated in smokers compared with nonsmokers (P < 0.05). These indexes of oxidative stress were markedly decreased (P < 0.001) in the smokers and nonsmokers after consumption of 280 mg dl-alpha tocopherol acetate/d for 10 wk. Platelet numbers in serum of both smokers and nonsmokers were also decreased by vitamin E supplementation (P < 0.02). Although the clinical significance of the results is unclear, elevated indexes of lipid peroxidation are associated with the pathogenesis of atherosclerosis, and platelets are involved with fibrinolysis. Therefore, both smokers and non-smokers may benefit from increased vitamin E intakes.

Blood Platelets↗
PubMed1992

Isolated ascending colon ulceration in a patient with chronic renal insufficiency.

Chronic renal hemodialysis or transplantation may be accompanied by a myriad of gastrointestinal problems. Ischemic bowel disease, spontaneous perforation diverticulitis, appendicitis, fistulae, and angiodysplasia have all been reported in the literature. Isolated colonic ulcerations have been described as a cause of both massive hemorrhage and spontaneous perforation. The exact predisposing factors are unknown. Ischemia, immunosuppression, and cytomegalovirus may play important roles in pathogenesis. This article describes a case of both hemorrhage and spontaneous colonic perforation accompanying end-stage renal disease in a patient who was not undergoing long-term dialysis or posttransplantation immunosuppression.

Aged↗
PubMed1991

Thymic stromal cells in culture. 2. Binding of normal thymocytes to a cloned thymic stromal cell line.

Thymic stromal cell line TS-9 was found to selectively bind a subpopulation of normal murine thymocytes. Selective binding allowed the isolation and phenotypic characterization of the adherent and nonadherent subpopulations of thymocytes. Flow cytometric analysis of fluorescently labeled thymocytes revealed that the adherent and nonadherent populations differ in maturity, with the adherent population enriched in immature thymocytes of the PNAhi, Thy-1hi, CD3-/lo, and CD4+/CD8+ double positive surface phenotype. A quantitative microwell assay was developed to measure the binding of thymocytes to TS-9. Thymocytes labeled with vital DNA stain Hoechst 33342 were allowed to bind to TS-9 in microwells and the intense fluorescence of this label was readily detected with a scanning fluorometer. The binding was trypsin-sensitive and hyaluronidase and PI-PLC resistant. The binding was also temperature dependent and sensitive to cytochalasin B. A panel of monoclonal antibodies to cell surface antigens including CD2, LFA-I/ICAM-I, and Thy-1 was screened in a quantitative binding assay for their ability to inhibit the binding of thymocytes to TS-9. The binding was partially inhibited by the C3C12 monoclonal antibody which recognizes the recently identified and apparently unique gp23,gp45 complex expressed on murine stromal cells.

Animals↗
PubMed1991

Thymic stromal cells in culture. I. Establishment and characterization of a line which is cytotoxic for normal thymocytes and produces hematopoietic growth factor(s).

Lines of thymic stromal cells have been established. One of these, designated TS-9, has been cloned and studied extensively. This line expresses both acid and alkaline phosphatases. Despite repeated cloning, TS-9 cells remain morphologically heterogeneous. The origin of these cells is not clear. They express low levels of immunologically identifiable cytokeratins, produce laminin, a basement membrane protein, but express antigens typically found on bone marrow stromal cells. The TS-9 cells are MHC Class I+ but Class II-. They express the Thy-1, Pgp-1, and Mac-2 antigens but not other lineage markers of T cells or macrophages. Coculturing TSC with normal thymocytes or with the CTLL-1 cell line leads to a profound inhibition of lectin-induced and/or IL-2 induced T cell proliferation. This requires direct cell-cell contact and ultimately results in the death of the bound lymphocytes. It cannot be reproduced by culturing the thymocytes with TSC culture supernatants. These supernatants do contain hematopoietic growth factor(s) which augment the growth of some T lineage cells and support the growth of monocytic colonies in semi-solid culture medium. Both normal thymocytes and a variety of T cell tumors bind to TSC but only the normal cells are killed as a consequence of this interaction. Neither the binding nor the killing appear to be MHC restricted. We suggest that this killing may provide a model for the effector mechanism of the negative selection imposed by the thymus on developing T cells.

Animals↗
PubMed1990

A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type I TAX1 with a responsive element in the viral long terminal repeat.

The human T-cell leukemia/lymphoma virus type I (HTLV-I) trans activator, TAX1, interacts indirectly with a TAX1-responsive element, TRE-2, located at positions -117 to -163 in the viral long terminal repeat. This report describes the characterization of a 36-kilodalton (kDa) protein identified in HeLa nuclear extract which mediates the interaction of TAX1 with TRE-2. Purification of the protein was achieved by zinc chelate chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The renatured 36-kDa protein bound specifically to a TRE-2 oligonucleotide but not to nonfunctional base substitution mutant probes in a gel retardation assay. Renatured proteins of differing molecular weights were unable to form this complex. In addition, the 36-kDa protein specifically activated transcription from the HTLV-I promoter in vitro. Purified TAX1 protein formed a complex with the TRE-2 oligonucleotide in the presence of the 36-kDa protein, suggesting that indirect interaction of TAX1 with the viral long terminal repeat may be one of the mechanisms by which HTLV-I transcription is regulated.

Cell Nucleus↗
PubMed1989

Baseline characteristics in the Hypertension Prevention Trial. Hypertension Prevention Trial Research Group.

The Hypertension Prevention Trial (HPT) was a randomized, controlled, multicenter (four clinics, four resource centers) trial designed to test the feasibility of achieving and sustaining dietary changes in the intake of calories, sodium, and potassium and to assess the effect of those changes on blood pressure in a normotensive population. The trial involved 841 men and women (plus a test cohort of 78) who, at the first baseline (BL) examination were in the age range of 25-49 years and had diastolic pressure (DBP) greater than or equal to 76 but less than 100 mm Hg (average of two readings), and at the examination prior to randomization (BL 2), had DBP greater than or equal to 78 but less than 90 mm Hg (also averaged). Participants were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary treatment groups involving counseling designed to reduce calorie intake; reduce sodium intake, reduce sodium and calorie intake, and reduce sodium and increase potassium intake. This chapter presents HPT baseline characteristics by weight stratum, clinic, and treatment group for various demographic, medical history, and nutritional characteristics, for several physiologic variables used in monitoring treatment compliance, and for blood pressure. The degree of comparability observed among treatment groups was within the range expected for the randomization procedure used.

Adult↗
PubMed1989

[3H]serotonin binding to blastula, gastrula, prism, and pluteus sea urchin embryo cells.

1. The presence of serotonin binding sites in blastula, gastrula, prism, and pluteus embryos of the sea urchin, Arbacia punctulata, was investigated by the binding of radiolabelled serotonin to dissociated embryo cells. 2. [3H]serotonin binding sites were identified in prism, early pluteus, and advanced pluteus larvae, but not in blastula or gastrula embryos. 3. The ontogeny of [3H]serotonin binding activity closely parallels that of serotonin content as previously reported in Paracentrotus lividus embryos (Toneby, 1977a). 4. Results of this study support a regulatory role of serotonin in developmental processes in postgastrula sea urchin embryos.

Animals↗
PubMed1987

Augmentation of IL 1-induced fibroblast PGE2 production by a urine-derived IL 1 inhibitor.

IL 1, a monocyte-derived cytokine, has potent biologic effects in a variety of target tissues. The existence of naturally occurring inhibitors of IL 1 activity has been recently described; these inhibitors blocked one IL 1 effect: stimulation of thymocyte responses to mitogens. We examined the effect of one well-characterized inhibitor of IL 1, isolated from the urine of febrile patients, on a second IL 1 effect, stimulation of fibroblast PGE synthesis. In this system, purified preparations of the urinary inhibitor that completely blocked murine thymocyte proliferative responses to mitogen failed to block PGE synthetic responses to IL 1. Rather, inhibitor preparations markedly enhanced fibroblast PGE synthetic responses to IL 1. When partially purified inhibitor preparations were fractionated by ion exchange chromatography, inhibitory activity for the IL 1 effect on thymocytes and PGE stimulatory activity co-eluted. Augmentation of the IL 1-induced PGE response was seen with both low (1:1 unit) and high (400:1) ratios of inhibitor to IL 1. Inhibitor preparations alone did not stimulate fibroblast PGE synthesis. The augmentation of fibroblast PGE synthesis by inhibitor preparations was not due to contaminating endotoxin. Active inhibitor preparations contained less than 15 pg of endotoxin/U activity, and the PGE stimulatory effect was not blocked by the addition of polymyxin B, whereas polymyxin B reversed the effects of exogenous endotoxin. It appears that the inhibition of IL 1 effects by naturally occurring inhibitors may have target cell and/or functional specificity.

Cells, Cultured↗
PubMed1987

Mechanism of action of a human interleukin 1 inhibitor.

The urine of febrile humans contains a 30- to 35-Kda glycoprotein (febrile inhibitor) that inhibits interleukin 1 (IL-1)-induced proliferation of murine thymocytes. In the present investigation, the mechanism of action of this febrile inhibitor was analyzed. The inhibitor was not cytotoxic for thymocytes and it did not act by inhibiting the uptake or incorporation of [3H]TdR. The effects of the inhibitor were not blocked by indomethacin, suggesting that it was not acting by a prostaglandin-mediated pathway. The inhibitor appeared to be acting at a later stage of the cell activation sequence, since it was still effective when added as late as 48 hr after the addition of IL-1. However, it did not block the ability IL-1 to bind and activate thymocytes but did block the proliferation of IL-1-primed cells. The inhibitor did not suppress the activation of thymocytes induced by concanavalin A, but did block the augmentation of this response by IL-1. These results suggest that the target of the febrile inhibitor is on IL-1-primed thymocytes, and that it acts at a stage after the initial activation of the cell by IL-1.

Animals↗
PubMed1987

Inositol phosphates accumulation in ovarian granulosa after stimulation by luteinizing hormone.

Accumulation of inositol phosphates by granulosa cells from medium follicles of porcine ovaries was studied to determine if hydrolysis of phosphoinositides is stimulated by luteinizing hormone (LH). Although follicle-stimulating hormone (FSH), D-alanine-gonadotropin-releasing hormone (D-ala-GnRH), and dibutyryl cyclic adenosine 3',5'-monophosphate (dbcAMP) had no effect, LH increased accumulation of inositol phosphate (IP), -bisphosphate (IP2), and trisphosphate (IP3) by severalfold. Furthermore, 0.01 microgram LH/ml increased IP3 accumulation threefold, while 0.1 microgram/ml stimulated accumulation of all inositol phosphates. Compared to untreated cells, LH-treated granulosa cells produced approximately twice as much progesterone in 30 min. Preincubation of cells with lithium chloride (LiCl) was necessary to measure IP accumulation, but not IP2 and IP3 accumulations. However, IP2 and IP3 accumulations were higher in LH-treated granulosa after pretreatment with LiCl. Maximal increases in IP3 and IP2 accumulations occurred approximately 15 min and 30 min, respectively, after LH stimulation, whereas the effect of LH on IP accumulation continued for at least 60 min. Granulosa, made permeable to IP3 with saponin treatment, did not hydrolyze [3H]IP3 to [3H]IP2 or [3H]IP. Thus, it is hypothesized that LH stimulates phosphoinositide hydrolysis in granulosa cells, thereby generating putative second messengers.

Animals↗
PubMed1986

Uromodulin, an immunosuppressive protein derived from pregnancy urine, is an inhibitor of interleukin 1.

Uromodulin, an 85-kDa glycoprotein isolated from pregnancy urine, has been shown to inhibit antigen-induced proliferation of human lymphocytes in vitro. The present investigation was undertaken to determine its mechanism of action. Uromodulin was found to be a potent inhibitor of interleukin 1 (IL-1)-induced thymocyte proliferation. Uromodulin was compared to a previously described 30- to 35-kDa IL-1 inhibitor isolated from urine of febrile patients (febrile inhibitor). Uromodulin and the febrile inhibitor blocked the effects of both human IL-1 and recombinant murine IL-1, but the activity of uromodulin was greater than that of the only partially purified febrile inhibitor preparation. However, in contrast to the febrile inhibitor, uromodulin markedly enhanced interleukin 2-induced thymocyte proliferation. Antigenic analysis of the two preparations by ELISA and immunoblot analysis demonstrated that the febrile inhibitor did not cross-react with uromodulin using monoclonal or polyclonal antisera. These findings indicate that uromodulin is a potent IL-1 inhibitor that is probably distinct from the IL-1 inhibitor derived from the urine of febrile individuals. Whether this IL-1 inhibitory activity underlies its immunosuppressive activity on human lymphocytes remains to be established.

Antibodies, Monoclonal↗
PubMed1986

Effect of macrophage activation on phagocyte-Plasmodium interaction.

We investigated the effect of both immune and normal sera on the binding of free Plasmodium berghei by resident and activated macrophages. Resident macrophages bound plasmodia to a greater extent than did activated macrophages, regardless of treatment. Resident macrophages bound free plasmodia, predominantly trophozoites, in the presence of normal serum by a mechanism inhibited by N-acetylglucosamine and N-acetylmannosamine. Macrophages activated through treatment with Propionibacterium acnes ("Corynebacterium parvum"), on the other hand, did not bind free plasmodia in the presence of normal serum through systems inhibited by N-acetylmannosamine or N-acetylglucosamine. The binding of free plasmodia by activated macrophages was greatest in the presence of immune serum and could be inhibited by immune complexes but not by N-acetylmannosamine or N-acetylglucosamine. These results suggest that a receptor for a carbohydrate component of a normal serum opsonin mediates initial adherence of plasmodial antigen onto resident macrophages, triggering both the immunological cascade and macrophage activation. After activation, the macrophages no longer have the carbohydrate-specific receptor but do have functional Fc receptors which mediate the adherence of immune-serum-opsonized plasmodia.

Animals↗
PubMed1985

Extrahepatic portal venous thrombosis: frequent recognition of associated diseases.

Twelve patients with obstruction of the extrahepatic portal venous system were seen at the Tufts-New England Medical Center between 1970 and 1979; a cause for the portal vein thrombosis was detected in 11. These included pancreatic disease (4); hematologic disorders (2); postoperative complications of laparotomy (3); transhepatic gelfoam embolization of the portal vein (1); and exchange transfusion via the umbilical vein (1). Clinical features included frequent self-limited episodes of bleeding from esophageal or gastric varices; and no characteristic or clinically helpful laboratory findings. The diagnosis was usually made in patients by identifying clots in the portal vein on selective angiography of the celiac and/or superior mesenteric arteries in which the venous phase was examined. Attempts at surgical correction were largely unsuccessful. Further thrombotic episodes occurred in three patients, and led to death in one. Two patients were given chronic anticoagulation with Coumadin and Persantin for 1 and 11/2 years, respectively without further thrombosis or gastrointestinal bleeding. However, it not yet possible to assess the risks and benefits of such therapy.

Adolescent↗