Biomedical subjects
J Watson
Publications and source records attributed to J Watson.
Professional identity crisis--is nursing finally growing up?
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Tympanometric changes after total maxillary osteotomy.
With the frequency of orthognathic surgery increasing each year, more is being learned about this surgical art. Although techniques are improving, more acute and chronic complications are being reported after orthognathic surgery. In our institution, it has been noticed that approximately 25% to 30% of our patients experience unilateral or bilateral otalgia after total (Le Fort I) maxillary osteotomy. Recently, two patients with maxillary osteotomies. In both patients acute otitis media developed postoperatively and myringotomies for relief of symptoms were required. This paper reports changes observed in preoperative and postoperative tympanograms of patients who undergo total maxillary osteotomy and offers a possible explanation for these middle ear changes, which are accompanied by otalgia.
Interleukin-2 induction of hapten-specific cytolytic T cells in nude mice.
In light of i) increasing evidence that the thymus guides the development and antigen recognition repertoire of cytotoxic T cells (CTL) and ii) the capacity of purified interleukin 2 (IL-2) to allow for the in vitro generation of CTL from nude mice, we investigated the ability of IL-2 to influence the in vitro generation of hapten-specific cytotoxicity from nude mouse spleen cell cultures. We found that stimulation of nude mouse splenocytes with trinitrophenol (TNP)-derivatized autologous or allogeneic spleen cells in the presence of IL-2 generated hapten-specific CTL. EFfector cells harvested from IL-2-supplemented cultures killed only TNP-derivatized target cells; however, the cytotoxicity observed was not restricted to a particular target histocompatibility type. This study confirms our previous observations that IL-2 has the capacity to induce growth of CTL from pre-T cell populations in the total absence of thymic influence. However, it is clear that the generation of H-2 restricted killing (recognition and lysis of cells bearing antigen presented solely in association with "self" H-2) probably requires further processing of pre-killer T cell populations by a thymus-derived differentiation signal. In addition, these studies provide further evidence that a major role of the thymus, in addition to programming effector T cell antigen recognition repertoire, may be its function to provide essential differentiation of the IL-2 producer T cell.
Biochemical and biologic characterization of lymphocyte regulatory molecules. VIII. Purification of interleukin 2 from a human T cell leukemia.
The ability of interleukin 2 (IL 2) to stimulate and maintain growth in IL 2-dependent cell lines distinguishes this substance from interleukin 1 and other T cell lymphokines. Jurkat-FHCRC, a human T cell leukemia cell line, has been shown to produce relatively high quantities of IL 2 after stimulation with the T cell mitogens phytohemagglutinin or concanavalin A. In this paper we describe techniques used to isolate human IL 2 from Jurkat supernatants and the biochemical properties of the resulting material. IL 2 produced by this cell line is eluted from a DEAE-Sephacel ion-exchange column with 0.05 M NaCl and has a m.w. determined by AcA54 gel chromatography in the range of 9000 to 18,000. Isoelectric focusing yields active material with a pI value of 7.75. Elution of IL 2 from a SDS-polyacrylamide gel shows it to have a m.w. of approximately 13,500. This material is capable of stimulating mouse as well as human IL 2-dependent cell lines.
Purification of murine helper T cell-replacing factors.
Humoral factors secreted by T lymphocytes and macrophages appear to play a role in cell communication leading to the triggering of immune responses. A factor has been purified from the culture supernatants of concanavalin A(Con A)-activated murine spleen cells with lymphokine activity in four assay systems. 1) stimulation of antibody responses to erythrocyte antigens in BALB/c.nu spleen cultures 2) amplification of production of cytotoxic T cells in thymocyte cultures, 3) stimulation of mitogenic responses to Con A in thymocyte cultures where the cell density is too low to support responses to Con A alone, and 4) maintenance of continuous T cell growth. The biologic activity has been sequentially purified by salt precipitation, gel filtration, chromatography, ion-exchange chromatography, and isoelectric focusing (IEF). These four lymphokine activities appear to be due to one class of molecules, termed Interleukin 2 (IL-2), with an apparent molecular weight of 30,000 daltons. A T cell lymphoma, LBRM-33 has been found to produce high titers of IL-2 activity upon mitogen stimulation. LBRM-derived IL-2 possesses similar chemical and biological properties to splenic-derived IL-2. The mode of action of IL-2 appears to be the clonal expansion of antigen- or mitogen-activated T cells. While mitogen-activated LBRM cells secrete IL-2, which appears to exert helper T cell-replacing activity via the expansion of pre-T cells in nude spleens, mitogen-activated spleen cells appear to secrete both IL-2 and another class of T cell-replacing factor (TRF). These findings raise the question of whether there exist multiple classes of factors with TRF activity. The identification of these molecules may lead to an understanding of the mechanism that regulates the induction of antigen-sensitive cells.
Antihypertensive medication regimens and their revision. A General Practitioner Clinical Research Group study.
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Some cytofluorimetric studies of the nuclear ploidy of mouse hepatocytes. I. A simple method for isolation of hepatocyte nuclei using in situ perfusion of the liver.
A simple method for isolating mouse hepatocyte nuclei is presented, which requires no special apparatus. Flow cytofluorimetric scans of hepatocyte nuclei, prepared by this method and stained with ethidium bromide, showed that adult mice have a high proportion of their hepatocyte nuclei in the tetraploid and octaploid states. Polyploidy was more pronounced in female animals.
Some flow cytofluorimetric studies of the nuclear ploidy of mouse hepatocytes. II. Early changes in nuclear ploidy of mouse hepatocytes following carbon tetrachloride administration: evidence for polyploid nuclei arrested in telophase.
Mature mice have a large proportion of their hepatocyte nuclei in polyploid states (tetraploid and octaploid), and this is more prominent in females. We measured nuclear ploidy distribution cytometrically using ethidium bromide-stained hepatocyte nuclei liberated by in situ collagenase perfusion of the liver via the portal vein. After s.c. administration of 0.2 ml carbon tetrachloride the ploidy distributions of 8-month-old female mice changed from a control of 35% 2N, 45% 4N, and 20% 8N to 54% 2N, 45% 4N and 1% 8N at 6 h, and 65% 2N, 35% 4N and 0% 8N at 24 h. By 72 h 92% of the nuclei were diploid. These changes preceded any changes in mitotic index and S-phase index (3H-TdR autoradiographs). Histology confirmed the loss of higher-ploid nuclei but without mitotic figures or selective cell necrosis to account for the observations. Cleaved nuclei were prominent in sections of liver examined 3 h after CCl4 administration and suggested division of polypoid nuclei that had undergone prior segregation of chromatids and had presumably been arrested in telophase.
Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line.
To isolate a stable tumor cell line capable of producing human interleukin 2 (IL-2; formerly referred to as T cell growth factor), 16 human T and B leukemia cell lines were screened for constitutive and mitogen-stimulated IL-2 production. We found that the T cell leukemia line designated Jurkat-FHCRC produced > 200 U/ml of IL-2 activity after a 24-h stimulation with T cell mitogens. Peak mitogen-induced IL-2 activity was found in supernates harvested from 24-h Jurkat-FHCRC cell cultures stimulated with either 1% phytohemagglutinin or 20 microgram/ml concanavalin A. Addition of the fatty acid derivative phorbol myristate acetate to mitogen-stimulated cultures increased Jurkat-FHCRC IL-2 production to concentrations > 400 U/ml. IL-2 activity observed in such cases represented between 100--300 times that produced in conventional cultures of mitogen- or alloantigen-stimulated normal human peripheral blood or splenic lymphocytes. Jurkat-FHCRC-derived conditioned medium demonstrated equal capacity to promote the sustained in vitro proliferation of either murine or human activated T cell lines confirming the ability of Jurkat-FHCRC cells to produce human IL-2. These studies identify a new source of human IL-2 and establish a valuable reagent for the isolation and further molecular characterization of this immunoregulatory molecule.
Biochemical separation of interleukin 2.
Interleukin 2 (IL-2) is a class of T cell growth factors produced by T cells of a number of species. The unique growth-promoting properties of these molecules allow the development of antigen-specific effector T cell lines which can be used to analyze the molecular basis of lymphocyte interactions. A murine T cell tumor line has been identified as a source of IL-2. The purification and biochemical properties of murine IL-2 are described, and compared with rat and human Il-2.
Stimulatory action of prostaglandin F2 alpha on androgen aromatization in the pig follicle.
Previous in vitro studies with pig tissues have demonstrated that follicle-stimulating hormone (FSH) can stimulate follicular prostaglandin F2 alpha (PGF2 alpha) production, and both FSH and PGF2 alpha can stimulate follicular estradiol production. The present study was designed firstly to confirm that in the pig, as in the rat, FSH increases estradiol production by stimulation of the aromatase enzyme system, and secondly to investigate the possibility that PGF2 alpha may play a role in the FSH stimulation of androgen aromatization. FSH increased the incorporation of [3H]testosterone into estradiol during a 3-h incubation of halved pig follicles or isolated granulosa cells by 85% compared to controls. PGF2 alpha increased the incorporation by 107%, whilst the two substances together caused an increase of 124%. Indometacin, an inhibitor of PG synthesis, reduced the incorporation of 21% of the control value, and completely inhibited the FSH stimulation. These results show that FSH stimulates the aromatase enzyme system of pig granulosa cells, and suggest that PGF2 alpha may play an obligatory role in androgen aromatization.
Cloning the Tra1 region of RP1.
The Tra1 region of RP1 from a derivative with Tn7 inserted into the kanamycin resistance determinant was cloned, using EcoRI, into the multicopy vector plasmid pBR325. For one orientation of the cloned fragment the resultant chimeric plasmid was very frequently lost from the cell, but in the other orientation it was much more stable and also compatible with RP1. Complementation by the stable chimeric plasmid, pED800, of a series of RP1 tra mutants showed that the mutations of all those retaining sensitivity to the P-specific phages PRR1, Pf3, and PR4, or only to PR4, mapped in the Tra1 region, while only 2 out of 20 amber mutations leading to full P-specific phage-resistance did so.
Characterization of T cell growth factors for the clonal analysis of recognition properties of T cells.
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Interleukin 2: a class of T cell growth factors.
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Non-invasive treatment of ununited fractures of the tibia using electrical stimulation.
A non-invasive method of electrical stimulation of healing in ununited fractures of the tibia by pulsed magnetic fileds has been evaluated. In a series of 17 patients all but two of the fractures united within 4 to 10 months, with an average time of just under six months. The method is sufficiently promising to merit further clinical investigation.
Biochemical characterization of lymphocyte regulatory molecules. II. Purification of a class of rat and human lymphokines.
Rat spleen cells activated in vitro by concanavalin A produce lymphokine molecules that possess biologic activity in a number of murine lymphocyte response assays. A single class of lymphokine most adequately described as T cell growth factor (TCGF, Interleukin-2) with a m.w. of 15,000 as estimated from gel filtration studies and with an isoelectric range of 5.4 to 5.6 stimulates i) the growth of established T cell lines in culture, ii) the proliferation of thymocytes in the presence of Con A under culture conditions where Con A alone is non-mitogenic, iii) the induction of antibody responses to heterologous erythrocyte antigens in athymic (nude) mouse spleen cell cultures, and iv) the generation of cytotoxic T lymphocytes (CTL) in thymocyte cultures and in nude mouse spleen cell cultures. We suggest that in each of the assay systems tested, this class of rat lymphokine acts directly on activated T cells. Nonactivated T cells must be stimulated by either mitogen or antigen before becoming responsive to lymphokine, but do not require antigen or mitogen for continued lymphokine-dependent proliferation. Similarly, human peripheral blood mononuclear cells activated by phytohemagglutinin (PHA) produce a class of lymphokines of identical size with an isoelectric point of 6.0 to 6.5 that possess the same biologic properties as measured in murine lymphocyte response systems.
Genetic control of the immune response to collagen. III. Coordinate restriction of cellular cooperation and antigen responsiveness by thymus-directed maturation.
The H-2 restriction of T helper cells from thymus-reconstituted nude mice was examined. Hybrid athymic mice were bred from BALB/c.nu and C57BL/6.nu parental strains and reconstituted with fetal thymus tissue from either parental strain. T helper cells from these mice, immunized to SRBC, were restricted to cooperation with B cells of the thymic H-2 haplotype. These T helper cells were shown to have originated from the F1 host by functional sensitivity to antisera and complement. The H-2 restriction of thymus-reconstituted F1 nude mice was further investigated by examining expression of the Ir-collagen phenotype. Results showed that the level of antibody produced in response to type I calf collagen in thymus chimeras correlates with the H-2 haplotype (high responder or low responder) of the reconstituting thymus. These experiments indicate that the thymus environment of T cell maturation influences both the H-2 restriction and Ir-phenotype of a responding immune system.