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Biomedical subjects

J Hudson

Publications and source records attributed to J Hudson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Requirements for Langerhans' cell depletion following in vitro exposure of murine skin to ultraviolet-B.

Langerhans' cells found within the skin and mucous membranes are critical regulators of antimicrobial and allergic responses. Therefore, the depletion of these cells following exposure of skin to solar ultraviolet radiation (UV) has direct functional consequences on immunity within this tissue. In order to understand how Langerhans' cell depletion is regulated following exposure of skin to medium-wave UV (UVB), the role of second messengers in these responses was investigated using a novel in vitro system. This was accomplished by analysing the expression of a specific marker associated with Langerhans' cells (ATPase) among the epidermal portion of cultured sections of mouse skin following treatment with inhibitors specific for second messenger components and subsequent exposure to UVB. In this study, inhibitors of guanosine triphosphate (GTP) binding proteins, H-8, pertussis toxin and cholera toxin as well as inhibitors of RNA and protein synthesis were all capable of blocking Langerhans' cell depletion in response to UVB treatment. In contrast, an inhibitor of protein kinase C (H-7) was incapable of specifically blocking depletion following treatment with this physical agent. These results suggest that Langerhans' cell depletion mediated by UVB may involve a pertussis and cholera toxin-sensitive G protein as well as de novo protein synthesis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Modulation of lymphohematopoiesis in long-term cultures by gamma interferon: direct and indirect action on lymphoid and stromal cells.

Gamma interferon (IFN-gamma) is the product of multiple cell types within the bone marrow microenvironment and has been demonstrated to act as a potent inhibitor of myelopoiesis in vitro and in vivo. The action of this cytokine on lymphohematopoiesis has now been examined on both long-term bone marrow cultures and representative cloned cellular components of the bone marrow microenvironment. In myelopoietic (Dexter) cultures, the half maximal inhibitory concentration of IFN-gamma was between 1 and 10 U/mL. In comparable lymphopoietic (Whitlock/Witte) cultures, IFN-gamma inhibited the production of B-lineage lymphoid cells with a half maximal effective concentration of less than 1 U/mL. In a clonal assay for pre-B cells, IFN-gamma inhibited colony formation with a half maximal concentration of 1 to 5 U/mL. Not all B-lineage lymphoid cells displayed the same sensitivity, however. Growth of the IL-7-dependent B cell line (2E8) in methylcellulose assays was unaffected by IFN-gamma while the replication of other lymphoid lines was partially or completely inhibited. IFN-gamma induced the expression of cell surface proteins (MHC Class I and II) on both B-lineage cells and stromal cells. In cloned stromal cell lines, IFN-gamma increased the steady state mRNA levels for the cytokines interleukin-6 (IL-6) and JE, a member of the IL-8 family. These data indicate that IFN-gamma acts within the lymphohematopoietic microenvironment through both direct and indirect actions on the hemopoietic and stromal cell populations.

Animals↗
PubMed1992

The wee1 protein kinase is required for radiation-induced mitotic delay.

Cellular feedback or 'checkpoint' mechanisms maintain the order of completion of essential, cell-cycle related functions. In the budding yeast, for example, the RAD9 gene product is required to delay progression into mitosis in response to DNA damage. Similarly, in fission yeast, the cdc25 and cdc2 gene products influence the ability of cells to delay mitosis in response to the inhibition of DNA synthesis. Because these two checkpoint controls regulate the same event, mitosis, we observed the effect of gamma-irradiation on cell cycle progression in fission yeast, to test whether the two controls require the same cell-cycle regulatory elements. We show that gamma-radiation-induced mitotic delay requires functional wee1 protein kinase but does not seem to involve the cdc25 pathway. Mitotic delay in response to DNA damage is thus distinct from the delay induced by inhibition of DNA synthesis, which involves cdc25 but is not dependent on wee1.

Cell Cycle Proteins↗
PubMed1992

A phase I trial of recombinant human macrophage colony-stimulating factor by rapid intravenous infusion in patients with refractory malignancy.

Twenty patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant macrophage colony-stimulating factor (rM-CSF). The rM-CSF was administered by intravenous bolus infusion for 5 consecutive days every other week for 2 treatment weeks. The doses administered ranged from 30 to 33,000 micrograms/m2/day. There was no intrapatient dose escalation. There were minimal to no systemic side effects seen, except for acute dyspnea noted in three patients. The dyspnea was felt to be related to the rate of infusion and did not recur in one patient given additional rM-CSF at a slower infusion rate. The major hematologic effect seen was a mild decrease in platelet count, which began to recover while the patients continued to receive the rM-CSF. The clearance of rM-CSF was dose dependent. Lower doses resulted in a saturable mechanism felt to represent cellular uptake. Clearance at higher doses demonstrated both a first-order mechanism at high serum rM-CSF concentrations, representing renal clearance, as well as a saturable mechanism at low serum concentrations. The maximum mean serum half-life was reached at dose levels of greater than or equal to 3,690 micrograms/m2 and was in the range of 234-258 min. By this route of administration, rises in absolute monocyte count were slight and seen only at doses of greater than or equal to 450 micrograms/m2 during the second therapy week. The maximum tolerated dose was not reached in this study because of lack of availability of rM-CSF.

Adult↗
PubMed1991

Cloning and characterization of the promoter of the murine lipoprotein lipase-encoding gene: structural and functional analysis.

The enzyme lipoprotein lipase (LPL) is responsible for the hydrolysis of triglycerides into free fatty acids and glycerol. Its synthesis is induced as the murine bone marrow stromal cell clone, BMS2, undergoes adipocyte differentiation. The murine genomic LPL promoter has been cloned, sequenced, and characterized by functional and structural assays. The transcriptional start points have been mapped by S1 nuclease and primer extension techniques. Comparison of the 1.7-kb of LPL 5'-flanking sequence between mouse and man reveals 65% identity or greater with conservation of many potential protein-recognition motifs. Using constructs linking this region to the luciferase-encoding reporter gene, transient transfection experiments have documented the promoter function of this sequence in a number of cell lines. Based on a battery of restriction endonucleases, at least 260 bp immediately adjacent to and including the 5'-untranslated region of the first exon are hypersensitive to exogenous nuclease digestion, consistent with an altered chromatin structure. Protein-DNA interactions are detected within this area at the octamer binding protein 1 site and immediately 5' to the translation initiation site based on ExoIII footprinting and gel retention assays.

Animals↗
PubMed1991

Tumor necrosis factor-alpha mRNA accumulation in human myelomonocytic cell lines. Role of transcriptional regulation by DNA sequence motifs and mRNA stabilization.

The cytokine TNF mediates many of the pathologic signs of cachexia, inflammation, and sepsis. The current work describes the regulation of TNF in human myelomonocytic cell lines after PMA stimulation. The cell lines exhibit a low level of constitutive TNF mRNA expression. Within 2 to 4 h of PMA exposure, steady state levels of TNF mRNA are markedly elevated in all myelomonocytic cell lines studied. This rise is due to increased mRNA stability, which increased by almost twofold, and to an overall increase in transcription, which rises by more than sixfold. At the level of the genomic TNF gene, a DNase I hypersensitive site is detected within the TNF promoter between -200 to -100 bp relative to the transcription initiation site. Although absent in nonexpressing erythroleukemia cell lines, the DNase I site is present in uninduced myelomonocytic cell lines and is not changed after PMA induction. The PMA induction of c-fos mRNA correlated well with TNF gene induction; expression of genes encoding other proteins in the AP-1 complex (junB and junD) were also induced by PMA. The nuclear extracts from resting and induced ML-1 cells contain proteins binding specifically to the AP-1, AP-2, and NF kappa B sequence located within the TNF promoter. PMA induction increases the level of a number of specific binding complexes relative to the resting cells. The regulatory mechanisms of the human and murine TNF genes are discussed.

Base Sequence↗
PubMed1991

Regulation of interleukin 6 expression in murine bone marrow stromal cells.

The regulation of interleukin 6 (IL-6) expression in the B-lymphocyte-supporting murine stromal cell line BMS2 has been examined in response to exogenous cytokines and chemical agents. Kinetic analyses of IL-6 mRNA induction and decay are presented together with analysis of the IL-6 biological activity. The cytokines tumor necrosis factor, interleukin 1 (alpha and beta), and transforming growth factor beta, as well as forskolin and dibutyryl cyclic AMP, all induce a transient rise in the steady-state level of IL-6 mRNA and an increased release of IL-6 protein. To study its regulation at the chromatin level, the murine IL-6 genomic gene has been cloned. Induction of IL-6 expression correlates with increased DNA nicking, consistent with increased topoisomerase I and endogenous nuclease activity. This finding is supported by kinetic analyses using camptothecin, a topoisomerase I inhibitor. We conclude that IL-6 regulation in murine stromal cells capable of supporting B-lymphopoiesis is comparable to that observed in human diploid fibroblasts.

Animals↗
PubMed1990

Altered hepatic clearance and killing of Candida albicans in the isolated perfused mouse liver model.

The adherence of Candida albicans was studied in situ by using the perfused mouse liver model. After exhaustive washing, 10(6) C. albicans were infused into mouse livers. At the time of recovery, 62 +/- 5% (mean +/- standard error of the mean) of the infused C. albicans were recovered from the liver and 14 +/- 3% were recovered from the effluent for a total recovery of 76 +/- 4%. This indicates that 86 +/- 3% of the original inoculum was trapped by the liver and that 24 +/- 4% was killed within the liver. Chemical pretreatment of C. albicans with 8 M urea, 12 mM dithiothreitol, 2% beta-mercaptoethanol, 1% sodium dodecyl sulfate, 10% Triton X-100, or 3 M potassium chloride or enzyme pretreatment with alpha-mannosidase, alpha-chymotrypsin, subtilisin, beta-N-acetyl-glucosaminidase, pronase, trypsin, papain, or lipase did not alter adherence of C. albicans to hepatic tissue. By contrast, pepsin pretreatment significantly decreased hepatic trapping. Simultaneous perfusion with either 100 mg of C. albicans glycoprotein per liter or 100 mg of C. albicans mannan per liter also decreased trapping. Furthermore, both substances eluted previously trapped C. albicans from hepatic tissue. Chemical pretreatment with 8 M urea, 12 mM dithiothreitol, or 3 M KCI or enzymatic pretreatment with alpha-mannosidase, subtilisin, alpha-chymotrypsin, or papain increased killing of C. albicans three- to fivefold within hepatic tissue. The data suggest that mannose-containing structures on the surface of C. albicans, for example. mannans or glucomannoproteins, mediate adherence of C. albicans within the liver. Indirectly, chemical and enzymatic pretreatment renders C. albicans more susceptible to hepatic killing.

Animals↗
PubMed1990

Standards and norms in small area analysis.

Description of the type and amount of variation in the use of health care services across geographic areas is a well-established method of inquiry encompassing the analysis of both medical and surgical treatment modalities.

Catchment Area, Health↗
PubMed1989

Interleukin 2 receptor expression in patients with head and neck squamous carcinoma. Effects of thymosin alpha 1 in vitro.

Altered cellular immunity in patients with advanced head and neck cancer includes impairments in lymphokine production, blastogenesis, in vitro cytotoxicity, and T-cell levels. Recent evidence for the potential importance of in lymphokine interleukin 2 (IL-2) in patients with cancer prompted a study of the kinetics of IL-2 receptor expression on lymphocytes from patients with untreated advanced head and neck cancer and normal subjects and an evaluation of the in vitro effects of the T-cell immune-reconstituting peptide, thymosin alpha 1. Concanavalin A-stimulated IL-2 receptor expression was maximal after 72 hours and was higher in normal subjects than in patients. This was due to lower levels of helper/inducer (CD4) cells expressing IL-2 receptors in the patients compared with the normal subjects. Thymosin alpha 1 further decreased levels of IL-2 receptor-positive (both CD4 and CD8) cells at 48 and at 72 hours. At 96 hours, levels of IL-2 receptor-positive cells and proportions of cells in G2 and M phases of the cell cycle were similar among both groups of subjects. Simultaneous cell kinetic studies indicated that thymosin alpha 1 down regulation of IL-2 receptors was not due to an effect on proliferation and that differences in IL-2 receptor expression at 72 hours among normal subjects and the patients with cancer were more likely related to differences in cell proliferation kinetics.

CD4 Antigens↗
PubMed1989

Effect of diagnostic and therapeutic cordocentesis on maternal serum alpha-fetoprotein concentration.

We investigated the affect of cordocentesis (n = 36) and intravascular transfusion (n = 14) performed with a fixed needle guide on maternal serum alpha-fetoprotein levels. In 50% of the procedures, the placenta was anterior and punctured. For all patients, maternal serum alpha-fetoprotein levels rose 70.8% +/- 28%. The magnitude of the rise was unrelated to the number of attempts necessary, gestational age, or the initial maternal serum alpha-fetoprotein levels concentration. The location of the placenta was the sole identified variable related to the rise. A total of 44% of the patients had a significant increase in maternal serum alpha-fetoprotein level when the placenta was anterior. In contrast, only 4% of the patients had a significant rise in maternal serum alpha-fetoprotein level when the placenta was other than anterior. There was no difference in the frequency of a significant rise in maternal serum alpha-fetoprotein level concentration between the patients who underwent cordocentesis and those who underwent intravascular transfusion. On the basis of these findings, we recommend that when maternal isoimmunization is a potential concern and the placenta is anterior, the umbilical cord should be approached either through a window or laterally from the placenta.

Amniocentesis↗
PubMed1988

Ammonium ion sensitivity is a ribosomal phenotype associated with suppressor mutations in the suaC gene of Aspergillus nidulans.

Ammonium ions are selectively toxic to strains containing mutations in the suaC gene which can mutate to a suppressor phenotype. This phenotype is associated with increased ribosomal misreading in vitro (Zamir and Martinelli 1987) and altered ribosomal proteins (Harvey and Martinelli 1983). Such ammonium-sensitivity is a feature of both strong and weak suppressor alleles, and segregates with suppressor ability in crosses. Suppressor mutations in the suaB and suaD genes are not affected, nor are those in suaA, another ribosomal suppressor gene. Thus, the ammonium-effect is locus specific. Mutations which act as anti-suppressors (asu-) of suppressor suaC109 also partially reverse the ammonium ion sensitivity associated with this mutation. This effect is in line with their restoration of other aspects of the pleiotropic phenotype to normal. The cations, lithium and rubidium, mimick the effects of ammonium ions. Only ribosomes from suaC strains are sensitive to the presence of NH+4 ions in vitro.

Ammonia↗
PubMed1988

Increased immunoglobulin response to gamma-interferon by lymphocytes from patients with systemic lupus erythematosus.

The factors responsible for abnormal B-cell activation in systemic lupus erythematosus (SLE) are incompletely understood. This study tested the hypothesis that the abnormal B-cell activation observed in human SLE may be due to an augmented response to a helper signal. We demonstrated that non-T cells from 10 of 19 SLE patients increased IgG production in response to interferon-gamma (IFN-gamma) by a mean factor of 20.9 +/- 3.9 over resting levels, while controls stimulated a mean factor of 3.0 +/- 0.5 (P less than 0.005). We found no relationship of IFN-gamma responsiveness to disease activity. Serotyping for HLA A, B, C, and D loci suggested that the hyperresponsiveness may be genetically linked to HLA-Cw7. We conclude that IFN-gamma may contribute to the development and perpetuation of SLE in a subset of patients with SLE.

Antibody Formation↗
PubMed1988

B cell activation in patients with active procainamide induced lupus.

Cellular immune abnormalities have been described in asymptomatic patients receiving procainamide therapy, but not in patients with active procainamide induced lupus. We tested patients with active procainamide lupus for evidence of T or B cell activation similar to that observed in idiopathic lupus. Symptomatic patients had a significant increase in spontaneous IgG synthesis, but T cells bearing activation markers were not significantly different from age matched controls. Our results demonstrate that patients with active procainamide lupus have evidence for B cell activation, similar to idiopathic lupus.

Aged↗
PubMed1987

Alterations in T-lymphocyte subpopulations in patients with head and neck cancer. Correlations with prognosis.

Impaired cell-mediated immunity has been consistently demonstrated in patients with advanced head and neck squamous cancer (HNSC); however, the results of prior studies of correlations of cellular immune parameters with treatment outcome have been inconsistent, and routine assessment of immune parameters has been of limited clinical use. To determine the prognostic importance of alterations in the proportions of various T-lymphocyte subpopulations in the peripheral blood of patients with HNSC, levels of T3, T4, T6, T8, T9, T10, T11, and Leu 7 cells were quantitated by flow cytometry in 80 previously untreated patients and prospectively correlated with tumor characteristics and clinical course (median length of follow-up, 27 months). The mean helper/suppressor cell ratio (T4/T8) increased progressively with increasing tumor stage and was significantly elevated among patients with cancer as a group and in patients with advanced (stage III or IV) disease compared with 40 normal subjects. Decreased disease-free survival was significantly associated with elevated T4/T8 ratios and low percent T8 and T11 cell levels. The prognostic significance of percent T8 (cytotoxic/suppressor) cell levels persisted even after adjusting for known prognostic factors of tumor stage, T class, N class, and tumor site. These correlations provide new insight into immune alterations in HNSC that may prove useful in identifying patients with early clinical disease who have a poor prognosis.

Adult↗
PubMed1987

Analysis of immediate-early and early proteins of murine cytomegalovirus in permissive and nonpermissive cells.

The immediate-early (IE) and early proteins induced by murine cytomegalovirus (Smith strain) in permissively infected 3T3-L1 murine fibroblasts were identified by SDS polyacrylamide gel electrophoresis. Ten proteins were classified as IE by their time of synthesis and by their synthesis in the presence of actinomycin D following reversal of a cycloheximide mediated protein synthesis block. By exclusion, seven proteins were classified as early class. Eleven of these proteins were precipitated by MCMV antiserum. The role of IE and early proteins in the replication of the virus was studied by infection of a murine macrophage cell line (J 774A.1) and human foreskin fibroblast (HFF) cells. The infections were characterized as nonpermissive by several criteria, including lack of production of infectious virus or viral DNA. However, the major IE and early MCMV proteins were detected in the nonpermissively infected cells. The block to virus replication in the macrophage and human fibroblast cells appeared to occur after the switch from IE to early protein synthesis, but before viral DNA replication.

Animals↗