Biomedical subjects

J S Moore

Publications and source records attributed to J S Moore.

At least 37 records · Page 2Linked to original sources

PubMed2000

Novel polymers: molecular to nanoscale order in three dimensions.

The assembly of polymer chains in solution is a powerful method that is leading to the preparation of interesting and unique macromolecular-based synthetic nanostructures. Specific control over the intramolecular and intermolecular physical interactions dictates either the folding of single chains or the aggregation and ordering of multiple chains. This control is provided through the selective placement of functional groups along the polymer backbone and the relative strengths of their attractive and repulsive interactions.

Journal Article↗

PubMed2000

Replacement of graft-resident donor-type antigen presenting cells alters the tempo and pathogenesis of murine cardiac allograft rejection.

BACKGROUND: Graft-resident antigen presenting cells (APCs) are potent stimulators of the alloresponse. To test whether replacement of graft-resident donor-type APCs with those of recipient-type alters allorecognition and the pathogenesis of both acute and chronic rejection, we created chimeric hearts for transplantation into naive recipients. METHODS: To replace donor-type APCs with those of recipient-type, chimeric animals were created by bone marrow transplantation (BMT) in fully allogeneic mouse and rat strain combinations. The degree of APC replacement in chimeric organs was assessed phenotypically and functionally. Chimeric hearts were transplanted heterotopically into untreated recipients. RESULTS: Flow cytometric and immunohistochemical analysis did not detect residual bone marrow recipient-type APCs in mouse BMT chimeras. Although semi-quantitative reverse transcription polymerase chain reaction detected 0.001-0.01% residual cells, APCs isolated from chimeric organs were functionally unable to stimulate donor-type cells. When transplanted into naive recipients, chimeric mouse hearts had significantly prolonged survival but were nevertheless rejected acutely. Similar results were obtained in the ACI --> LEW rat strain combination. However, in the PVG --> DA rat model, the majority of chimeric hearts survived >100 days and all long-surviving hearts developed cardiac allograft vasculopathy. CONCLUSIONS: BMT leads to near complete replacement of organ-resident APCs. The virtual absence of donor-type APCs in chimeric hearts delays or prevents acute rejection in a strain-dependent manner. In contrast, this type of graft modification does not prevent cardiac allograft vasculopathy. This suggests that, although the CD4+ direct pathway may play a role in acute rejection, it is not essential for the development of chronic rejection in rodent cardiac allografts.

Acute Disease↗

PubMed2000

Classification criteria and severity assessment in work-associated upper extremity disorders: methods matter.

Work-associated musculoskeletal disorders of the upper extremity are common and disabling. Research on these disorders is needed and requires valid methods of classification of the disorders for epidemiologic studies and measurement of their impact on functional status. This commentary discusses the methodologic aspects of classification and functional status assessment in upper extremity musculoskeletal disorders.

Classification↗

PubMed2000

Flexor tendon entrapment of the digits (trigger finger and trigger thumb).

Flexor tendon entrapment of the digits is a disorder characterized by snapping or locking of the thumb or fingers (with or without pain). Most cases are secondary to thickening of the digit's A1 pulley, but other pathogeneses include tendon abnormalities at the level of the carpal tunnel, thickening of other pulleys, and abnormalities of the metacarpal-phalangeal joint. Its historical name, stenosing tenosynovitis of the digits, is inappropriate because histological studies document a lack of inflammation. Flexor tendon entrapment of the digits is a relatively common, uncomplicated, and non-controversial musculotendinous disorder of the distal upper extremity. The purpose of this invited review is to summarize information from the medical literature on aspects of this condition likely to be of interest and relevant to occupational medicine practitioners. Topics covered include normal anatomy and kinesiology, history, clinical observations related to diagnosis, pathology, pathophysiology, clinical observations on etiology, descriptive epidemiology, epidemiological studies, and case management. Models for the pathogenesis of flexor tendon entrapment of the digits are proposed, and opportunities for future research are presented.

Fingers↗

PubMed1999

Hypoxia-mediated apoptosis from angiogenesis inhibition underlies tumor control by recombinant interleukin 12.

The role of angiogenesis inhibition in the antitumor activity of recombinant murine interleukin 12 (rmIL-12) was studied in K1735 murine melanomas, the growth of which is rapidly and markedly suppressed by rmIL-12 treatment. On the basis of the prediction that tumor ischemia should result from therapeutic angiogenesis inhibition, tumor cell hypoxia was evaluated as a marker of ischemia using the EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)aceta mide] approach. This method measures intracellular binding of the nitroimidazole EF5, which covalently binds to cellular macromolecules selectively under hypoxic conditions. Whereas 1 week of rmIL-12 treatment effectively inhibited K1735 cell-induced angiogenesis in Matrigel neovascularization assays, 2 weeks of treatment were needed before severe tumor cell hypoxia was detected in K1735 tumors. The hypoxia that developed was regional and localized to tumor areas distant from blood vessels. The great majority of severely hypoxic tumor cells were apoptotic, and in vitro studies indicated that the degree of hypoxia present within treated tumors was sufficient to trigger K1735 apoptosis. Tumor cell apoptosis was also prevalent in the first week of rmIL-12 treatment when few cells were hypoxic. In vitro studies indicated that this non-hypoxia-related apoptosis was induced directly by IFN-gamma produced in response to rmIL-12 administration. These studies reveal that rmIL-12 controls K1735 tumors initially by IFN-gamma-induced apoptosis and later by hypoxia-induced apoptosis. They also establish hypoxia as an expected result of tumor angiogenesis inhibition and a mediator of its therapeutic effect.

Animals↗

PubMed1999

Community health workers: examining the Helper Therapy principle.

A community approach to the integration of health and social services for low-income pregnant women is being addressed through Community Integrated Service System (CISS) initiatives of the Maternal Child Health Bureau. This particular CISS program model was designed to enable low-income mothers to function in a Community Health Worker (CHW) role providing social support for at-risk pregnant women. Using Riessman's notion of "helper therapy," the model was also developed to enhance the potential for CHWs to gain helper benefits. The purpose of this exploratory study was to describe perceived helper benefits and stressors associated with the CHW role and to examine the usefulness of an instrument developed to assess benefits and stressors. The study findings revealed that the majority of CHWs perceived helper benefits that included positive feelings about self, a sense of belonging, valuable work experience, and access to health information and skills through training or contact with program staff. Stressors such as feeling inadequate to help, however, were associated with the helper role for some CHWs. Preliminary analysis of the Helper's Perception Measure indicated that it may be an effective measure and should be tested with a larger sample of CHWs.

Adult↗

PubMed1999

Modulation of 11beta-hydroxysteroid dehydrogenase isozymes by growth hormone and insulin-like growth factor: in vivo and in vitro studies.

The interconversion of hormonally active cortisol (F) and inactive cortisone (E) is catalyzed by two isozymes of 11beta-hydroxysteroid dehydrogenase (11betaHSD), an oxo-reductase converting E to F (11betaHSD1) and a dehydrogenase (11betaHSD2) converting F to E. 11betaHSD1 is important in mediating glucocorticoid-regulated glucose homeostasis and regional adipocyte differentiation. Earlier studies conducted with GH-deficient subjects treated with replacement GH suggested that GH may modulate 11betaHSD1 activity. In 7 acromegalic subjects withdrawing from medical therapy (Sandostatin-LAR; 20-40 mg/month for at least 12 months), GH rose from 7.1 +/- 1.5 to 17.5 +/- 4.3 mU/L (mean +/- SE), and insulin-like growth factor I (IGF-I) rose from 43.0 +/- 8.8 to 82.1 +/- 13.7 nmol/L (both P < 0.05) 4 months after treatment. There was a significant alteration in the normal set-point of F to E interconversion toward E. The fall in the urinary tetrahydrocortisols/tetrahydocortisone ratio (THF+allo-THF/THE; 0.82 +/- 0.06 to 0.60 +/- 0.06; P < 0.02) but unaltered urinary free F/urinary free E ratio (a marker for 11betaHSD2 activity) suggested that this was due to inhibition of 11betaHSD1 activity. An inverse correlation between GH and the THF+allo-THF/THE ratio was observed (r = -0.422; P < 0.05). Conversely, in 12 acromegalic patients treated by transsphenoidal surgery (GH falling from 124 +/- 49.2 to 29.3 +/- 15.4 mU/L; P < 0.01), the THF+allo-THF/THE ratio rose from 0.53 +/- 0.06 to 0.63 +/- 0.07 (P < 0.05). Patients from either group who failed to demonstrate a change in GH levels showed no change in the THF+allo-THF/THE ratio. In vitro studies conducted on cells stably transfected with either the human 11betaHSD1 or 11betaHSD2 complementary DNA and primary cultures of human omental adipose stromal cells expressing only the 11betaHSD1 isozyme indicated a dose-dependent inhibition of 11betaHSD1 oxo-reductase activity with IGF-I, but not GH. Neither IGF-I nor GH had any effect on 11betaHSD2 activity. GH, through an IGF-I-mediated effect, inhibits 11betaHSD1 activity. This reduction in E to F conversion will increase the MCR of F, and care should be taken to monitor the adequacy of function of the hypothalamo-pituitary-adrenal axis in acromegalic subjects and in GH-deficient, hypopituitary patients commencing replacement GH therapy. Conversely, enhanced E to F conversion occurs with a reduction in GH levels; in liver and adipose tissue this would result in increased hepatic glucose output and visceral adiposity, suggesting that part of the phenotype currently attributable to adult GH deficiency may be an indirect consequence of its effect on tissue F metabolism via 11betaHSD1 expression.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1998

Novel approach for simultaneous evaluation of cell phenotype, apoptosis, and cell cycle using multiparameter flow cytometry.

Apoptosis is a vital process for organism development and, when disrupted, can lead to abnormalities including cancer and autoimmune diseases. We demonstrate a novel multicolor flow cytometry approach for quantifying apoptosis and cell cycle information of phenotypically distinct populations, using less than 2 x 10(5) cells per sample. We used incorporation of Cy5-dUTP into DNA strand breaks by the terminal dUTP nucleotide end labeling (TUNEL) method to determine apoptosis, while cell cycle information was assessed with an ultraviolet DNA binding dye, DAPI. To simultaneously determine surface phenotype, we used paraformaldehyde fixation and a gentle permeabilization protocol combined with FITC- and PE-labeled surface antibodies. Using these fluorochromes, and three-laser instrumentation, we quantified apoptosis and cell cycle phase in lymphocyte subpopulations from heterogeneous human and murine cell sources, subjected to various culture conditions. Further, we used this method to detect divergent rates of apoptosis in a human, heterogeneous lymphocyte tumor population, demonstrating a potential application for clinical and/or research settings. Thus, we describe a six-parameter, four-color flow cytometry approach for evaluating apoptosis and cell cycle with dual surface labels. This method may also be useful as a generalized scheme to assess simultaneously two intracellular targets in a mixed cell population.

Animals↗

PubMed1998

Aberrant responses of human lymphocytic neoplasms to cytokine regulation.

Studies in this laboratory have recently focused on two hemic neoplasms: B cell chronic lymphocytic leukemia (B-CLL) and a T cell disorder, Sézary syndrome. These tumors do not have consistent cytogenetic or molecular genetic alterations, and so we have concentrated on their response to and production of various regulatory cytokines. Although B-CLL cells show variable proliferative responses when exposed to transforming growth factor beta (TGF beta), these cells have consistently shown resistance to the pro-apoptotic effects of this cytokine. Also, interleukin 4 (IL4), IL5, and interferon-gamma (IFN gamma) all show a consistently increased protective effect against apoptosis in B-CLL cells as compared to normal human B cells. Thus, a defect in apoptosis appears to be an important factor in the pathogenesis of CLL. By contrast, the neoplastic T cells of Sézary syndrome show a consistent resistance to the antiproliferative effects of TGF beta, suggesting that aberrant proliferation is more important than apoptosis in this disorder. In both neoplasms, we have shown that the defective responses to cytokines are in some instances related to alterations in receptor expression, but this has not been true in all circumstances, and other stages in the signaling pathways are being investigated. As we define more precisely the specific defects that contribute to the clonal expansion of these neoplasms, the findings may ultimately lead to improved clinical control of these disorders.

Apoptosis↗

PubMed1997

Solvophobically driven folding of nonbiological oligomers.

In solution, biopolymers commonly fold into well-defined three-dimensional structures, but only recently has analogous behavior been explored in synthetic chain molecules. An aromatic hydrocarbon backbone is described that spontaneously acquires a stable helical conformation having a large cavity. The chain does not form intramolecular hydrogen bonds, and solvophobic interactions drive the folding transition, which is sensitive to chain length, solvent quality, and temperature.

Acetonitriles↗

PubMed1997

Analysis of tumor thiol concentrations: comparison of flow cytometric with chemical and biochemical techniques.

The importance of glutathione (GSH) in contributing to cancer therapy resistance is well established. Various advantages may accrue from the ability to determine the distribution of GSH content in individual tumor cells disaggregated from solid tumors using flow cytometric techniques compared with biochemical or chemical measurements of the average GSH level in bulk tissue samples. The flow cytometric technique requires a thiol-reactive fluorescent adduct which is stable and which can differentiate cellular GSH from protein thiols. Thiol-reactive compounds specific for GSH require facilitated conjugation by endogenous cellular enzymes, but such compounds have not been found to accurately monitor GSH in human cells. Compounds which react generally with all thiols require a GSH-depleted calibration control to assess GSH vs. non-GSH components of fluorescent-adduct formation. Our report addresses this question, and compares three different thiol assays in several cell lines. We have found a simple way to control for non-GSH adduct formation. This involves a selective permeabilization process to release low molecular weight adducts (dominated by GSH and cysteine). In application to the desired goal of assessing the distribution of GSH in cells disaggregated from tumors, we have identified a problem with cell-line-specific thiol loss during the tumor cell disaggregation process.

Animals↗

PubMed1997

Altered response to and production of TGF-beta by B cells from autoimmune NZB mice.

New Zealand Black (NZB) mice spontaneously develop immune dysfunction manifested as autoimmune hemolytic anemia and systemic lupus erythematosus. In later life, a subset of these mice develop clonal CD5+ B cell tumors analogous to human chronic lymphocytic leukemia (CLL). NZB disease is marked by B cell hyperactivity characterized by spontaneous immunoglobulin secretion and proliferation. Elimination of autoreactive lymphocytes by apoptosis is a vital mechanism to prevent expansion of self-reactive lymphocyte population. TGF-beta appears to be an important factor in normal and abnormal immune regulation and this cytokine may play a role in the development of chronic human B cell tumors. We asked whether the response to or production of TGF-beta by NZB B cells was aberrant and could contribute to disease development. In this study, we demonstrated that the apoptotic response to TGF-beta was increased in B cells from NZB mice compared to B cells from normal BALB/c mice. The increased apoptosis was related to endogenous activation and was possibly mediated through increased expression of the TGF-beta Type II receptor. Despite functional differences between CD5-negative B cells and CD5-positive B cells, TGF-beta induced apoptosis in both populations to a similar extent. NZB B cells also secrete increased active TGF-beta compared to BALB/c B cells. We suggest that the aberrant secretion of active TGF-beta and the increased response to the apoptotic effects of TGF-beta by NZB B cells may play a role in the disease process of these mice, perhaps attempting to limit the autoimmune phenomena, but possibly also contributing to generalized immunosuppression. We also suggest that the CD5(+) tumors in the NZB mouse may not be a fully appropriate model of human CLL, since CLL B cells are abnormally resistant to the apoptotic effects of TGF-beta.

Age Factors↗

PubMed1997

Chronic lymphocytic leukemia B cells are resistant to the apoptotic effects of transforming growth factor-beta.

Chronic lymphocytic leukemia (CLL) is the most common leukemia of the western world and is characterized by a slowly progressing accumulation of clonal CD5+ B cells. Our laboratory has investigated the role of transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) in the pathogenesis of B-cell expansion in CLL. In vitro addition of TGF-beta did not increase spontaneous apoptosis of B cells from most CLL patients, as determined using the TUNEL method, compared with a twofold increase observed in cultures of normal B cells. There was similar expression of TGF-beta type II receptors on both CLL B cells and normal B cells. In contrast to apoptosis, CLL B-cell proliferation was variably inhibited with addition of TGF-beta. In vitro addition of IL-4, previously reported to promote CLL B-cell survival, dramatically reduced spontaneous apoptosis of CLL B cells compared with normal B cells. CLL B-cell expression of IL-4 receptors was increased compared to normal B cells. Thus, our results show aberrant apoptotic responses of CLL B cells to TGF-beta and IL-4, perhaps contributing to the relative expansion of the neoplastic clone.

Apoptosis↗

PubMed1997

Creation of chimeric hearts: a tool for testing the "passenger leukocyte" hypothesis.

BACKGROUND: Bone marrow-derived antigen-presenting cells (APCs) are thought to be a migratory component of organ allografts that activate the rejection response, and recently they have been postulated to play a critical role in tolerance induction. Our goal was to create chimeric hearts (organs with parenchyma and APCs of differing genotype) for use in models of transplantation to test the "passenger leukocyte" theory. METHODS: Murine bone marrow transplantation were performed in two fully major histocompatibility complex (MHC) mismatched strain combinations: C3H-->B10 and CBA-->BALB/c. Recipients were lethally irradiated (10 Gy) and then received 1 x 10(7) bone marrow cells intravenously. Bone marrow transplant survivors had their organ APCs isolated by digestion with collagenase D, followed by density gradient centrifugation. The APC-enriched fraction was stained with fluorescein-labeled monoclonal antibodies specific for either donor (I-Ak) or recipient (I-Ab/d) class II MHC antigens, which are expressed by all APCs but not by parenchymal cells. Donor and recipient class II expression was determined by flow cytometry. RESULTS: Sixty-nine of 100 (69.0%) of C3H-->B10 and 52/107 (48.6%) of CBA-->BALB/c bone marrow transplant recipients survived more than 100 days, whereas all B10 (n = 12) and BALB/c (n = 10) irradiation controls died within 14 days. Mortality appeared to be caused by engraftment failure as most recipients died before day 20. Flow cytometry demonstrated complete APC replacement in hearts (n = 17) and spleens (n = 40), as APC-enriched fractions stained only for donor class II MHC antigens. CONCLUSION: Bone marrow transplantation leads to replacement of heart APCs in two murine models. Chimeric hearts are now being used to test the role of APCs in allograft rejection and in tolerance induction.

Animals↗

PubMed1997

Concurrent diagnosis of chronic lymphocytic leukemia and myelodysplastic syndrome.

An elderly patient is described with concurrent presentation of chronic lymphocytic leukemia and myelodysplastic syndrome, documented by clinical and hematological findings, flow cytometry and cytogenetics. The chromosome data suggested that these disorders developed as separate clones from two different hematopoietic precursor cells in this patient.

Aged↗

PubMed1997

Preliminary evaluation of a sensory and psychomotor functional test battery for carpal tunnel syndrome: Part 2--Industrial subjects.

This study evaluated the Wisconsin functional sensory and psychomotor test battery for carpal tunnel syndrome (CTS). Subjects were 27 employees recruited from a food processing plant. Both hands of all subjects were examined and categorized by presence or absence of symptoms and nerve conduction study (NCS) findings (Symptom-/NCS-, Symptom+/NCS-, Symptom-/NCS+, and Symptom+/NCS+). Symptom-/NCS- category hands had significantly better performance (15-60%) for most of the functional test battery variables than Symptom+/NCS+ category hands. A significant gap detection threshold difference (32%) was observed between NCS+ and NCS- hands regardless of symptoms, with NCS- having impaired performance. No significant effect of CTS symptoms on performance was observed. Stepwise discriminant analysis was used to select the best variables to differentiate between groups. The ratio of the change in pinch rate with respect to required pinch force differentiated NCS+ from NCS- hands, with a sensitivity of 0.71 and a specificity of 0.68. The same variable had a sensitivity of 0.74 and specificity of 0.83 for distinguishing Symptom-/NCS- hands from all other categories. Pinch rate had a sensitivity of 0.82 and a specificity of 0.81 for separating Symptom+/NCS+ hands from all other categories. Use of both gap detection threshold and the ratio of the change in pinch rate with respect to required pinch force could best differentiate Symptom+/NCS+ from Symptom-/NCS- cases for a sensitivity of 0.91 and specificity of 0.87. Outcomes could not be generalized to a specific work population but demonstrate that the non-invasive test battery may be useful for providing objective measures of deficits associated with CTS symptoms and electrophysiological parameters.

Adult↗

PubMed1997

Participatory ergonomics in a red meat packing plant. Part II: Case studies.

Three ergonomics-related case studies are presented to demonstrate the problem-solving method used by two participatory ergonomics teams. The problem-solving method was adapted from principles related to quality management (e.g., participation, structure, a scientific approach, and decision by consensus). The first two steps of the problem-solving method were related to identification and evaluation of the problem; the latter three steps were related to solution development, implementation, and evaluation. The problem evaluation process included the collection of background, exposure, and effects data. Solution development following evaluation of the problem started with a brainstorming session, then discussion to select interventions by consensus. The format for presenting the case studies was intended to be concise and visual with the intent of effectively documenting the teams' problem-solving processes.

Ergonomics↗

PubMed1997

De Quervain's tenosynovitis. Stenosing tenosynovitis of the first dorsal compartment.

De Quervain's tenosynovitis is a disorder characterized by pain on the radial (thumb) side of the wrist, impairment of thumb function, and thickening of the ligamentous structure covering the tendons in the first dorsal compartment of the wrist. It is precisely defined as stenosing tenosynovitis of the first dorsal compartment. It is a relatively common, uncomplicated, and noncontroversial musculoskeletal disorder of the distal upper extremity. The purpose of this review is to summarize information from the medical literature on aspects of De Quervain's tenosynovitis likely to be of interest and relevant to occupational medicine practitioners. The topics covered include normal anatomy and kinesiology; history; clinical observations related to diagnosis; pathology; pathophysiology; clinical observations on etiology; descriptive epidemiology; epidemiological studies; and case management. Models for the pathogenesis of De Quervain's tenosynovitis are proposed and opportunities for future research presented.

Case Management↗