Biomedical subjects

M R Smith

Publications and source records attributed to M R Smith.

At least 163 records · Page 9Linked to original sources

PubMed1990

Direct evidence for an intracellular role for tumor necrosis factor-alpha 1. Microinjection of tumor necrosis factor kills target cells.

TNF-alpha is a small peptide cytokine produced primarily by activated macrophages. One of the many biologic activities of TNF is the killing of diverse types of tumor cells. We considered the possibility that killing was mediated by TNF itself at an intracellular site, subsequent to receptor-mediated endocytosis. To test this hypothesis, we microinjected TNF into various murine normal cells and cell lines, some of which were killed by TNF given by the usual extracellular route, and others that were not. Cytotoxic effects of microinjected TNF were observed in several cell types 2 to 4 h after injection. L929 fibroblasts were killed by either extracellular or intracellular TNF. A TNF-resistant subline of L929 was insensitive to either extracellular or intracellular TNF. L6 fibroblasts were found to be resistant to high doses of TNF given either extracellularly or microinjected. Normal macrophages and the J774 macrophage-like cell line were not killed by extracellular TNF, but were rapidly killed by microinjected TNF. Thus, TNF, an extracellular peptide ligand, has an intracellular activity, suggesting that internalization of this ligand may have important intracellular biochemical roles.

Animals↗

PubMed1990

The biodegradation of aromatic hydrocarbons by bacteria.

Aromatic compounds of both natural and man-made sources abound in the environment. The degradation of such chemicals is mainly accomplished by microorganisms. This review provides key background information but centres on recent developments in the bacterial degradation of selected man-made aromatic compounds. An aromatic compound can only be considered to be biodegraded if the ring undergoes cleavage, and this is taken as the major criteria for inclusion in this review (although the exact nature of the enzymic ring-cleavage has not been confirmed in all cases discussed). The biodegradation of benzene, certain arenes, biphenyl and selected fused aromatic hydrocarbons, by single bacterial isolates, are dealt with in detail.

Bacteria↗

PubMed1990

A comparison of models used as alternative magnetic resonance image reconstruction methods.

In magnetic resonance (MR) imaging, excellent reconstructions are obtained on large data sets using the inverse discrete Fourier transform (IDFT). Modeling procedures have been proposed to overcome the image artifacts from the truncation of small data sets. In this paper, a relationship between image reconstruction using modeling and the standard IDFT is presented. A comparison of the assumptions behind the Smith and Haacke models is given and an experimental evaluation of the validity of the models provided. Various methods of evaluating model coefficients are discussed. Images are reconstructed from both models using the Transient Error reconstruction approach (TERA) algorithm. TERA is an algorithm that reintroduces data information components that cannot be modeled: useful when the assumed model characteristics do not completely match all portions of the image. Although very different in their basic assumptions, both the Smith and Haacke models were found to reduce truncation artifacts and improve resolution when used with the TERA algorithm.

Algorithms↗

PubMed1990

Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes.

The type I human T-cell leukemia virus (HTLV-I) encodes a 40-kD nuclear trans-regulatory protein termed Tax that transcriptionally activates the HTLV-I long terminal repeat (LTR), as well as select [corrected] cellular and heterologous viral promoters. Tax does not bind DNA specifically but, rather, acts in a more indirect manner. Tax activation of the HTLV-I LTR is mediated through constitutively expressed cellular factors that bind to cAMP response elements (CREs) present within the 21-bp enhancers of the LTR. In contrast, Tax transactivation of the interleukin-2 receptor-alpha gene (IL-2R alpha) and LTR of the type 1 human immunodeficiency virus (HIV-1) involves the induced nuclear expression of NF-kappa B. We now report the identification of missense mutations within the tax gene that functionally segregate these two pathways of trans-activation. Additionally, we demonstrate that the carboxyl terminus of the Tax protein, despite its acidic and predicted alpha-helical structure, is completely dispensable for trans-activation through either of these transcription factor pathways. Finally, we demonstrate that mutations within a putative zinc finger domain disrupt the nuclear localization of Tax and abolish trans-activation. These results demonstrate that Tax trans-activation of viral and cellular promoters involves at least two mechanisms of host transcription factor activation and suggest that this activation is likely mediated through distinct functional domains.

Amino Acid Sequence↗

PubMed1990

Induction of transformation and DNA synthesis after microinjection of raf proteins.

Full-length and N-terminal deletion mutants of human c-raf-1 cDNA were cloned into Escherichia coli expression plasmids. Bacterially expressed c-raf proteins were purified by anion-exchange, gel filtration, and affinity chromatography. Microinjection of mutant c-raf proteins into G0-arrested NIH 3T3 cells induced DNA synthesis and morphological transformation, whereas microinjection of full-length c-raf had no effect. The amino terminus of the raf protein has an important negative regulatory influence; alteration of this region resulted in increased kinase activity and oncogenicity.

Animals↗

PubMed1990

Lymphomas: MR imaging contrast characteristics with clinical-pathologic correlations.

Mean pixel intensity ratios, contrast parameters, and T1-T2 cross products relative to fat and muscle were derived from T1-weighted and T2-weighted images obtained at 1.5 T in 32 patients with non-Hodgkin lymphomas and 20 with Hodgkin disease. Lymphomas were relatively homogeneous: Only 6% of the lesions had broad, bimodal, or skewed distributions of pixel intensities that could be attributed to intrinsic heterogeneity. On average, lymphomas were hypointense to fat and slightly hyperintense to muscle in T1-weighted images but isointense to fat and hyperintense to muscle in T2-weighted images. Low-, intermediate-, and high-grade non-Hodgkin lymphomas had identical imaging characteristics. The most striking and significant result was the greater brightness of lymphomas with dense fibrosis in T2-weighted images, which explains the trend toward greater brightness of Hodgkin disease than that of non-Hodgkin lymphomas and greater brightness of lymphomas in the mediastinum than of lymphomas in other locations. Neither a contrast parameter nor the T1-T2 cross product added information not evident with the use of simple mean pixel intensity ratios.

Adolescent↗

PubMed1990

Translation initiation factors induce DNA synthesis and transform NIH 3T3 cells.

Several polypeptide factors that are essential for the initiation of protein synthesis bind to eukaryotic mRNAs and facilitate the formation of ribosome initiation complexes. Purified mRNA-binding translation initiation factors were microinjected into quiescent NIH 3T3 cells to study the possible growth-promoting role of these factors in living cells. We report that recombinant eIF-4E and rabbit reticulocyte eIF-4F induce a dose-dependent increase of DNA synthesis and morphologically transform NIH 3T3 cells. These results suggest that polypeptides involved in activating the rate-limiting step of protein synthesis (initiation complex formation) can be mitogenic and oncogenic when overexpressed in a cell by direct injection. Thus, eIF-4E and eIF-4F represent a class of proto-oncogenic proteins that is cytoplasmic, is involved in protein synthesis initiation, and is distinct from the proto-oncogenes that have been identified previously.

Animals↗

PubMed1990

[Staphylococcus aureus endocarditis in a puerperal woman with mitral and tricuspid valve prolapse].

A 17-year-old woman with mitral and tricuspid valve prolapse and myxomatous degeneration presented puerperal infection by Staphylococcus aureus with clinical picture of sepsis and multiple septic embolism (right eye, left thumb, spleen, and left calf). She underwent total hysterectomy on the 10th day postdelivery and right eye enucleation on the 16th. Temporary total AV block occurred on the 14th day with temporary external pacing during the next couple of days. Acute endocarditis with acute mitral regurgitation was diagnosed on the 13th day, demanding immediate valve replacement. On the 46th day she developed moderate tricuspid valve regurgitation due to another episode of endocarditis. Final clinical discharge took place on the 62nd day after antibiotic therapy completion.

Adolescent↗

PubMed1990

Circulating and secretory antibodies to specific food proteins in adults.

Indirect enzyme-linked immunosorbent assays (ELISA) for the detection of antibodies to gliadin, beta-lactoglobulin and ovalbumin have been developed. Specific antibody immunoglobulin levels were quantified. Serum and saliva samples were collected from twenty normal subjects and measured for the presence of specific antibodies. For each subject food intake was calculated from a 7-d weighed food inventory record. The total IgG level was 14.2 +/- 4.3 mg/ml (mean +/- s.d.). Levels of beta-lactoglobulin IgG were significantly lower than ovalbumin IgG levels (130 +/- 130 micrograms/ml versus 637 +/- 703 micrograms/ml, P less than 0.01). Gliadin IgG levels were also significantly lower than ovalbumin IgG levels (262 +/- 398 micrograms/ml versus 637 +/- 703 micrograms/ml, P less than 0.05). However, no significant difference was observed between gliadin and ovalbumin IgA levels in the subjects (29 +/- 39 per cent versus 56 +/- 122 per cent). A significant correlation was observed between ovalbumin IgG levels in serum and dietary intake of egg protein (r = 0.46, P less than 0.05). No other significant correlations were observed.

Adult↗

PubMed1989

The use of band-selectable digital filtering in magnetic resonance image enhancement.

Manipulation of the data describing two-dimensional magnetic resonance (MR) images can be used to zoom an image, decrease image noise and artifacts by modeling, or emphasize object edges in the field of view. In this paper, a two-dimensional band-selectable digital filtering (2D-BSDF) technique is detailed. This can be used to decrease the computational burden and increase algorithm stability associated with such data manipulation. Many display devices have the ability of expanding an image by pixel or linear interpolation. Application of the efficient zooming fast Fourier transformation algorithms provides a superior quality sinc-function interpolated image. In 2D-BSDF, the ideal rectangular windows used in sinc-function interpolation are replaced by windows with a more gradual roll-off. This gradual roll-off results in a slight degradation of the image edges but substantially reduces the computation time. Modeling of MRI data has been attempted to remove noise and artifacts from the image. These algorithms are computationally expensive and frequently unstable because of the high model orders required. The 2D-BSDF can be used to prepare a reduced data set, without loss of information. A lower order model may be applied to the subset and computation times approaching that required for normal fast Fourier transform algorithms result. The absence of noise and signal from objects outside the region of interest can considerably enhance the stability of the modeling algorithms. The use of BSDF is equally applicable when used in association with the modeling of 2D NMR spectroscopy data or with edge enhancement or any other data manipulation of magnetic resonance imaging images. In this paper an explanation of 1D-BSDF is provided and an algorithm for 2D-BSDF is developed. A comparison of filter designs and computational times is given when applying the technique to zooming and modeling of MR images. Images from medical MRI data are provided.

Algorithms↗

PubMed1989

Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors.

Twenty-eight patients with a uterine stromal sarcoma or mixed mesodermal tumor were treated with cisplatin 100 mg/m2 and Adriamycin 45-60 mg/m2, given with intravenous hydration every 3 to 4 weeks. Group I consists of 11 patients with measurable disease following initial surgery or with a recurrence. Eight of the eleven evaluable patients with measurable disease had a response (73%), and three of these patients have had a negative second-look procedure, and two are alive and disease free more than 24 months after initiation of treatment. Group II consists of 17 patients treated with adjuvant chemotherapy after primary surgery. The patients were selected for adjuvant therapy based on previous established poor prognostic features. Of the 17 patients in group II, 14 had invasion of the outer one-third of the myometrium and the other three had invasion to the middle one-third. Seven had documented positive pelvic and/or periaortic lymph nodes and five had positive peritoneal washings. With a median follow-up of 34 months, there have been only four recurrences in group II. Two of the recurrences occurred in patients who discontinued therapy after only two cycles of chemotherapy. There is a projected 5-year survival of 75% in these high-risk patients. Of the seven patients with documented nodal involvement, one patient died with a recurrence at 23 months, one patient died from a perforated diverticulum, and the other five are alive and disease free with a median follow-up of 36 months (34-90 months). Two patients with multiple positive nodes are disease free at more than 5 years. Combination chemotherapy with cisplatin and Adriamycin has a high response rate with advanced measurable disease and improves survival in high-risk patients who receive it as adjuvant therapy.

Adult↗

PubMed1989

The perception of rhythm and word boundaries in noise-masked speech.

The present experiment tested the suggestion that human listeners may exploit durational information in speech to parse continuous utterances into words. Listeners were presented with six-syllable unpredictable utterances under noise-masking, and were required to judge between alternative word strings as to which best matched the rhythm of the masked utterances. For each utterance there were four alternative strings: (a) an exact rhythmic and word boundary match, (b) a rhythmic mismatch, and (c) two utterances with the same rhythm as the masked utterance, but different word boundary locations. Listeners were clearly able to perceive the rhythm of the masked utterances: The rhythmic mismatch was chosen significantly less often than any other alternative. Within the three rhythmically matched alternatives, the exact match was chosen significantly more often than either word boundary mismatch. Thus, listeners both perceived speech rhythm and used durational cues effectively to locate the position of word boundaries.

Cues↗

PubMed1989

S-phase induction and transformation of quiescent NIH 3T3 cells by microinjection of phospholipase C.

Two inositol phospholipid-specific phospholipase C (PLC) isozymes (PLC-I and -II) have been purified from bovine brain. When PLC-I or PLC-II was microinjected (100-700 micrograms/ml) into quiescent NIH 3T3 cells, a time- and dose-dependent induction of DNA synthesis occurred, as demonstrated by [3H]thymidine incorporation into nuclear DNA. In addition, approximately to 8 hr after PLC injection, NIH 3T3 fibroblasts appeared spindle-shaped, refractile, and highly vacuolated, displaying a morphology similar to transformed cells. The morphologic transformation was apparent for 26-30 hr after which the injected cells reverted back to a normal phenotype. Microinjected PLC at a high concentration (1 mg/ml) was cytotoxic, dissolving the cytoplasmic membrane and leaving behind cellular ghosts. PLC is a key regulatory enzyme involved in cellular membrane signal transduction. Introduction of exogenous PLC into NIH 3T3 cells by microinjection induced a growth and oncogenic potential, as demonstrated by the ability of microinjected PLC (approximately 10,000 molecules per cell) to override the cellular G0 block, inducing DNA synthesis and morphologic transformation of growth-arrested fibroblast cells.

Animals↗

PubMed1989

The same 50-kDa cellular protein binds to the negative regulatory elements of the interleukin 2 receptor alpha-chain gene and the human immunodeficiency virus type 1 long terminal repeat.

We have investigated the biochemical basis for negative regulation of interleukin 2 receptor alpha-chain (IL-2R alpha) gene expression. Transient transfection studies employing internally deleted forms of the IL-2R alpha promoter localized a negative regulatory element (NRE) between nucleotides -400 and -368 relative to the major distal transcription start (cap) site. This 31-base-pair (bp) element is involved in the attenuation of both basal and inducible IL-2R alpha promoter activity. Comparison of this IL-2R alpha NRE with other known regulatory motifs revealed an 11-bp core element (TTCATCCCAGG) that was strikingly similar to a protein-binding domain within the long terminal repeat of the type 1 human immunodeficiency virus (HIV-1). This viral domain has been previously implicated in the negative control of HIV-1 gene expression. In vitro protein-DNA binding studies demonstrated that the same constitutively expressed approximately 50-kDa protein (SP-50) specifically bound to both the IL-2R alpha and HIV-1 NRE core elements. Mutation of the 11-bp IL-2R alpha NRE core element, which disrupted protein binding, significantly augmented basal as well as Tax protein- or phorbol ester-induced IL-2R alpha promoter activity in vivo, suggesting that SP-50 functions as a transcriptional silencer.

Base Sequence↗

PubMed1988

IL-1 is an autocrine growth factor for T cell clones.

Activation of Th lymphocytes requires that Ag be presented on the surface of accessory cells displaying Ia Ag. A number of studies have concluded that the T cell also requires IL-1 from accessory cells. However, we recently reported that one murine T cell clone (D10.G4.1) produced its own IL-1-like activity after encountering APC (9). In this report, we demonstrate that 1) IL-1 production is a common property of murine T cell clones, 2) T cell IL-1 activity is blocked by anti-IL-1-alpha antiserum, 3) IL-1-alpha mRNA can be directly visualized in individual cloned T cells using in situ hybridization techniques, and 4) IL-1 appears to serve an autocrine role in the activation of T cell clones inasmuch as anti-IL-1-alpha antiserum blocks cell proliferation when the T cell is the only IL-1 source.

Animals↗

PubMed1988

Detection of IL-1 alpha and IL-1 beta gene expression by in situ hybridization. Tissue localization of IL-1 mRNA in the normal C57BL/6 mouse.

IL-1 is a cytokine with a wide variety of effects on cells involved in inflammatory and immune responses, hemopoiesis, and bone formation. Many cell types have been shown to produce IL-1 in vitro; however, very little is known about the source and role of IL-1 in vivo. By using in situ hybridization, we examined the tissue distribution of cells containing IL-1 mRNA in normal C57BL/6 mice. The results show that many organs contain IL-1 mRNA-positive cells, but the highest frequency was found in lymphoid organs. The distribution and localization of these cells suggest that many of the IL-1 mRNA-producing cells are tissue macrophages. Organs exposed to environmental Ag and microbial products (lymph nodes, liver, intestine, lung, and uterus) had high frequencies of IL-1 mRNA-producing cells, suggesting that IL-1 is produced in local inflammatory or immune responses in vivo. The production of IL-1 mRNA in the thymus and in the bone marrow suggests that IL-1 is available to play physiologic roles in T cell differentiation and in hemopoiesis.

Animals↗

PubMed1988

Efficient algorithms for generating interpolated (zoomed) MR images.

This paper discusses the two-dimensional implementation of a number of modified fast Fourier transform (FFT) algorithms that efficiently interpolate (zoom) magnetic resonance (MR) images. If the original image was sampled at a rate satisfying the Nyquist criterion, these algorithms would effectively increase the sampling rate, permitting image details to be more easily discerned. The Skinner interpolating fast Fourier transform (SIFFT) avoids many of the computationally unnecessary complex multiplications that occur when interpolating using the normal fast Fourier transform algorithm. The novel interpolating fast Fourier transform (NIFFT) offers further savings when a subimage is required. Theoretical and experimental timings that compare the use of the normal FFT, SIFFT, and NIFFT algorithms for interpolation are given using magnetic resonance image reconstruction examples. Time savings of a factor of 2 to 4 are possible in typical experimental situations. Time savings of factors of 5 to 20 are possible when zooming images using two-dimensional band selectable digital filtering (2D-BSDF) in combination with decimation and the SIFFT algorithm. In 2D-BSDF, the original MRI data set is reduced in size to retain only those frequency components corresponding to a desired subimage, thereby decreasing the computational load associated with further processing. A significant reduction in computation time is achieved when modeling is combined with 2D-BSDF and SIFFT as fewer points require modeling.

Algorithms↗

PubMed1988

Discrepant changes in plasminogen by two different assays in patients receiving streptokinase.

The fluorogenic synthetic substrate and radial immunodiffusion assays of plasma plasminogen were compared before and after administration of intravenous streptokinase in differing doses to 57 patients being treated for acute myocardial infarction. There was a moderate correlation (r = 0.73, slope = 0.221, intercept = 1.005, n = 57 pairs) in the two assays of plasma plasminogen before the administration of streptokinase. After streptokinase, however, the correlation of the two assays was poor (r = 0.28, slope = 0.03, y-intercept = 0.003, n = 57 pairs). The decrease in plasma plasminogen by the fluorogenic synthetic substrate assay after streptokinase averaged 95 +/- 5%, with little variation between doses. In contrast, the percentage decrease in plasma plasminogen after streptokinase by the radial immunodiffusion assay averaged only 30 +/- 11%. The percentage change in plasma plasminogen by the two assays is significantly different (P = 0.001). The discrepancy in the percentage change in plasma plasminogen after streptokinase as measured by the fluorogenic synthetic substrate assay and the radial immunodiffusion assay can be explained by a lack of specificity for the antibody to plasminogen in the radial immunodiffusion kit. Antigen-antibody precipitin rings were observed after incubation of antibody with a mixture presumed to contain plasmin, plasmin-alpha 2 antiplasmin complexes, and plasmin-fibrin/fibrinogen degradation products. Based on these data, the fluorogenic synthetic substrate assay for plasma plasminogen is a superior means of following plasminogen depletion in response to thrombolytic therapy after streptokinase treatment for acute myocardial infarction.

Dose-Response Relationship, Drug↗