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D Moody

Publications and source records attributed to D Moody.

At least 19 recordsLinked to original sources
PubMed2001

The A' and F' pockets of human CD1b are both required for optimal presentation of lipid antigens to T cells.

CD1 proteins are unique in their ability to present lipid Ags to T cells. Human CD1b shares significant amino acid homology with mouse CD1d1, which contains an unusual putative Ag-binding groove formed by two large hydrophobic pockets, A' and F'. We investigated the function of the amino acid residues that line the A' and F' pockets of CD1b by engineering 36 alanine-substitution mutants and analyzing their ability to present mycobacterial glycolipid Ags. Two lipid Ags presented by CD1b were studied, a naturally occurring glucose monomycolate (GMM) isolated from mycobacteria, which contains two long alkyl chains (C54-C62 and C22-C24) and synthetic GMM (sGMM), which includes two short alkyl chains (C18 and C14). We identified eight residues in both the A' and F' pockets that were involved in the presentation of both GMM and sGMM to T cells. Interestingly, four additional residues located in the distal portion of the A' pocket were required for the optimal presentation of GMM, but not sGMM. Conversely, nine residues located between the center of the groove and the F' pocket were necessary for the optimal presentation of sGMM, but not GMM. These data indicate that both the A' and F' pockets of human CD1b are required for the presentation of lipid Ags to T cells.

Alanine↗
PubMed2000

A model for a multicentre approach to the derivation of reference intervals for thyroid hormones and testosterone for laboratories using identical analysers.

Ideally, every laboratory should derive their own reference intervals for all analytes, but this is difficult in practice. A survey, by questionnaire, of UK laboratories using the Chiron Diagnostics ACS:180 (Chiron Diagnostics Limited, Halstead, Essex, UK), for thyroid function tests, showed that 10% of laboratories derived their own reference intervals, 60% quoted values "adapted" from intervals for previous methods, whilst the remaining 40% quoted (often incorrectly) reference intervals supplied by the manufacturer. In addition only 13% of respondent laboratories derived their own reference intervals for testosterone. As a result of this survey, a study was devised to enable the users of the Chiron Diagnostics ACS:180 immunoassay system to develop and use within-method, between-laboratory reference intervals for thyroid hormones and testosterone. Laboratory collaboration provided the recommended minimum number of data points by establishing a reference sample group. This sample group was used for the calculation of appropriate reference intervals for each hormone according to the guidelines published by the IFCC. We propose this approach as a model for laboratories using identical instrumentation to produce, through collaboration, within-method, between laboratory reference intervals.

Female↗
PubMed1997

Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy.

In the attempt to develop immunotherapeutic strategies for acquired immunodeficiency syndrome capable of activating effector cells in an antigen-specific manner while maintaining the broadest possible T-cell repertoire, we evaluated two canarypox (ALVAC)-based vectors for their capacity to induce ex vivo activation/expansion of human immunodeficiency virus (HIV)-specific CD8+ cytotoxic lymphocyte precursors (CTLp) obtained from HIV-1-infected donors. These two vectors, vCP205 encoding HIV-1 gp120 + TM (28 amino acid transmembrane anchor sequence) in addition to Gag/protease and vCP300 encoding gp120 + Gag/protease as well as Nef and Pol CTL determinants, are pancytotropic but replication incompetent in mammalian cells. Bulk peripheral blood mononuclear cells (PBMCs) or enriched CD8+ T cells were stimulated for 10 days with autologous ALVAC-infected PBMCs in the presence of different cytokine combinations (interleukin-2 [IL-2], IL-4, IL-7, and IL-12). Activation by ALVAC constructs was highly antigen-specific, because vCP205 elicited only Env and Gag CTL, whereas vCP300 elicited broader reactivities against Env, Gag, Pol, and Nef determinants. The ALVAC activation of CTLp was IL-2 dependent and enhanced by the addition of IL-7, whereas IL-4 and IL-12 failed to augment cytotoxic reactivities elicited by these constructs. The expansion of enriched CD8+ T cells after activation with vCP300 was higher in patients with CD4 counts greater than 400 cells/microL. Two rounds of in vitro stimulation (IVS) with vCP300 resulted in nearly an eightfold expansion of CD8+ lymphocytes over a 25-day period. After the second IVS, an average 3.2-fold increase among the different antigen-specific CTL frequencies was achieved. These studies clearly show that HIV-recombinant ALVAC vectors represent powerful polyvalent antigenic stimuli for activation and expansion of the CD8 lymphocyte response that occurs as a result of HIV infection.

Adult↗
PubMed1997

The value of preoperative mammograms in nononcologic breast surgery.

It remains unclear whether preoperative mammograms are necessary in young patients having nononcologic breast surgery. Various authors have recommended mammography in all such cases, in conflict with guidelines from the American Cancer Society. We conducted a retrospective study to determine the utility of preoperative mammograms in young women. From 1989 through 1994, 208 patients under 35 years of age had elective breast surgery in our institution. Fifty-one (24.5%) had preoperative mammography. No malignancies were diagnosed. We believe mammograms are not routinely needed before elective breast surgery in patients under 35 years of age.

Adolescent↗
PubMed1997

A physical map of the Mamestra configurata nucleopolyhedrovirus genome and sequence analysis of the polyhedrin gene.

The genome structure of a nucleopolyhedrovirus (NPV) isolated from the bertha armyworm, Mamestra configurata Walker (Lepidoptera: Noctuidae) (MacoNPV) was analysed with six restriction endonucleases (REN): BamHI, EcoRI, HindIII, PstI, SmaI and Xhol. More than 70 MacoNPV REN fragments were cloned into plasmids pUC18 and pBluescript SK(+). The physical map with 112 restriction sites for the above REN was constructed using double digests and Southern blot hybridization analysis of the MacoNPV DNA clones. The size of the DNA genome of the MacoNPV-90/2 isolate used for this study was estimated at 156 kbp based on REN fragment sizes. The position of the polyhedrin gene, which has by convention been used as the zero point of the REN maps of NPV, was determined by hybridizing the Autographa californica multicapsid nucleopolyhedrovirus HindIII-V fragment clone, which contains most of the polyhedrin gene, with genomic blots of MacoNPV. The cloned MacoNPV fragments identified as containing the polyhedrin gene were sequenced and an ORF coding for a 246 amino acid polypeptide with 98.7% sequence identity with Panolis flammea nucleopolyhedrovirus (PaflNPV) polyhedrin protein was identified. The putative polyhedrin gene sequence had 97.2% and 91.2% identity with the PaflNPV and Mamestra brassicae multicapsid nucleopolyhedrovirus polyhedrin gene sequences, respectively, and also contained an upstream region identical to the highly conserved 12 bp consensus sequence TGTAAGT-AATTT typical of NPV very late genes.

Amino Acid Sequence↗
PubMed1996

Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells.

Studies to determine if Toxoplasma gondii-specific human T cells lyse parasite-infected cells have yielded conflicting results. Furthermore, attempts to obtain human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a reproducible system for their generation. By using paraformaldehyde-fixed, T. gondii-infected peripheral blood mononuclear cells as antigen-presenting cells, we developed a method whereby T. gondii-specific T-cell lines can be reproducibly generated. Six T. gondii-specific T-cell lines were generated from an individual chronically infected with T. gondii. Cytofluorometric analysis of these lines revealed > 99% CD3+, 85 to 95% CD3+ alpha beta T-cell-receptor-positive (TCR+), 5 to 9% CD3+ gamma delta TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells were examined during the first 3 weeks of stimulation and >99% CD3+, >99% CD3+ alpha beta TCR+, < 1% CD3+ gamma delta TCR+, 20 to 40% CD4+, and 60 to 80% CD8+ cells when cells were examined between 5 and 11 weeks. Both CD4+ and CD8+ T cells had remarkable cytotoxic activity against T. gondii-infected target cells (30 to 50% specific Cr release at an effector-to-target ratio of 30:1) but not against uninfected target cells ( < 10% at an effector-to-target ratio of 30:1). Cytotoxic activity by the whole T-cell lines was not T. gondii strain specific. Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49 strains and the RH strain (which was used to infect peripheral blood mononuclear cells). T. gondii-specific T-cell lines displayed the predominant expression of V beta 7 TCR. The CDR3 regions of the V beta 7 TCRs of these T-cell lines showed a striking degree of sequence identity (oligoclonality). T-cell lines obtained by the method reporter here can be used to characterize functional activity of T-lymphocyte subsets in humans infected with T. gondii.

Amino Acid Sequence↗
PubMed1994

Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.

OBJECTIVES: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. DESIGN: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts > 50 and 200 x 10(6)/l, respectively. METHODS: Autologous CD8 T cells (10(8)-10(10)) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rIL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. RESULTS: Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24-week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposi's sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-alpha, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-alpha induction. In one of the two patients studied, KS regression was associated with decreased IL-1 alpha serum levels. In the other patient, who had failed previous IFN-alpha therapy, KS regression was observed after a decline in reinfused CD8 cell-associated gene expression of tumor necrosis factor (TNF)-beta. Both IL-1 alpha and TNF-beta are growth factors for KS cells. CONCLUSIONS: These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rIL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1-associated disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus.

Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.

AIDS-Related Complex↗
PubMed1993

A phase 1 study of adoptive transfer of autologous CD8+ T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS.

Based on preclinical studies showing that CD8+ T lymphocytes of human immunodeficiency syndrome (HIV)-infected subjects have anti-HIV activities, a phase 1 study was undertaken to determine the safety and feasibility of infusing in vitro purified, activated, and expanded CD8+ cells as a therapeutic measure in seven patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Autologous CD8+ cells were first selectively isolated in monoclonal antibody-coated flasks from peripheral blood mononuclear cells recovered by leukapheresis. They were then cultured and expanded with phytohemagglutinin and recombinant interleukin-2 (rIL-2) before infusion. Five cycles of isolations and infusions of increasing numbers of CD8+ T cells were achieved in five of seven subjects. Five cycles could not be completed in two subjects with AIDS whose CD4+ cell counts were < or = 48/microliters. Infusions of CD8+ cells alone were well tolerated. Four patients received rIL-2 by continuous infusion for 5 days with their final cycle of CD8+ cells. All developed reversible adverse effects attributable to rIL-2. After infusion, 111In-labeled CD8+ cells quickly accumulated in the lungs, with less than 10% of the labeled cells remaining in the circulation. After 24 hours, labeled CD8+ cells were reduced in the lungs, but increased and persisted in liver, spleen, and bone marrow. Four of five patients who were treated with multiple infusions of CD8+ cells have improved or remained clinically stable, and the fifth developed Pneumocystis carinii pneumonia but recovered. This study demonstrated that infusion of autologous, in vitro expanded and activated CD8+ cells was feasible and clinically well tolerated in five of seven subjects with advanced HIV infections.

AIDS-Related Complex↗
PubMed1992

Health for all?

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Health Services Needs and Demand↗
PubMed1992

Production of monoclonal antibodies against the B700 murine melanoma antigen and their antimetastatic properties.

Two unique murine melanoma antigens, termed B700 and B50, have been identified and isolated from several different murine melanoma cell lines. Both antigens can be detected on the cell surface, are actively shed in culture, and are often found in close association intracellularly. In previous studies, the antigen B700, which is related to serum albumin by biochemical and immunological criteria, was shown to function as a melanoma-specific tumor rejection antigen. We have also shown that animals sensitized to irradiated JB/RH melanoma cells produce antibodies which recognize B700 and/or B50, with B700 evoking the stronger humoral response. Animals testing positive by ELISA for antibody production to B700 or B50 were used for preparation of hybridomas and four different murine monoclonal antibodies have been produced whose specificities should facilitate epitope mapping. Clones have been used to generate ascites fluid in nude mice; the antibodies specifically recognize B700 and intact murine melanoma cells, but not B50. Two of these monoclonal antibodies have been administered systemically to C57Bl/6 mice bearing 5 day pulmonary metastases of the JB/MS melanoma, and significant inhibition of metastatic growth was observed for both antibodies.

Animals↗
PubMed1990

Cauda equina syndrome complicating ankylosing spondylitis.

The cauda equina syndrome is an uncommon and poorly understood complication of ankylosing spondylitis. The clinical and radiologic findings in five patients with this syndrome are described. Typical findings include cutaneous sensory impairment of the lower limbs and perineum with sphincter disturbances. Motor impairment occurs less frequently, and associated pain is an inconstant feature. Enlargement of the caudal sac and dorsal arachnoid diverticula that erode the lamina and spinous processes are characteristic myelographic and computed tomographic findings. The pathogenesis of the cauda equina syndrome in ankylosing spondylitis remains unknown but may be due to demyelination, post-irradiation ischemia, or compression from spinal arachnoiditis.

Adult↗
PubMed1989

The intracellular association of B700 and B50 murine melanoma antigens and their role in tumor rejection.

B700 and B50 are melanoma-specific antigens originally isolated from B16 murine melanoma. B700, which elicits a strong tumor rejection response, is present on all murine melanomas tested to date. We now demonstrate the presence of B50 in the other murine melanomas and find that the 2 molecules are non-covalently complexed with each other within the cells. We also show that hosts immunized with intact, irradiated melanoma cells produce antibodies that specifically recognize the B700 and B50 tumor antigens. These results suggest that B50 may also participate in the host response to melanoma growth.

Animals↗
PubMed1984

Prospective evaluation of changes in computed cranial tomography in patients with small cell lung carcinoma treated with chemotherapy and prophylactic cranial irradiation.

Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.

Aged↗
PubMed1982

Vertical and horizontal sound localization in primates.

Minimum audible angles for localization in the vertical and horizontal planes were psychophysically determined in Old World monkeys (Macaca). In the vertical condition the test stimuli consisted of primate vocalizations and bands of noise. Minimum audible angles ranged from 3 degrees to greater than 20 degrees for signals of various bandwidths. The acuity of vertical localization was dependent upon the high-frequency content of the signal. Two of the three monkeys were unable to vertically localize sounds if the high-frequency limit of the signal was below 2000 Hz. The acuity of horizontal localization was tested for pure tones 500, 2000, and 8000 Hz in frequency, positioned at several referent locations in the right frontal quadrant. The acuity of horizontal localization decreased as the test azimuth was displaced from the midline. Minimum audible angles ranged from approximately 4 degrees to greater than 20 degrees and varied as a function of test azimuth.

Animals↗
PubMed1979

The trapped temporal horn: a trap in neuroradiological diagnosis.

Although the advent of computerized cranial tomography (CT) has decreased the number of pneumoencephalograms performed for the diagnosis of hydrocephalus and lesions of the posterior fossa, brain stem, and ventricles, there are some patients in whom pneumoencephalography should still be done because it adds valuable information to that obtained with CT. When the temporal horn becomes obstructed, the choroid plexus and ependymal surface "upstream" from the obstructing mass continue to produce cerebrospinal fluid (CSF). The temporal horn can thus enlarge enough to appear as a mass on CT because of its reduced x-ray attenuation coefficient. Pneumoencephalography is effective in this situation because air will flow past a mass that obstructs CSF and because the ventricular system dilates during pneumoencephalography. When pneumoencephalography is used in a patient with a trapped temporal horn, the partially trapped horn may enlarge approximately 24 hours later. With that precaution in mind, the neurosurgeon should find pneumoencephalography to be a useful adjunct to CT in delineating the cause of a trapped temporal horn. In the three patients reported here CT had indicated a unilateral trapped temporal horn; pneumoencephalography confirmed that finding and demonstrated both the location and the nature of the lesion. One patient had a Grade II astrocytoma fungating into the atrium of the right lateral ventricle, one had a mass extending into the right ventricle from the medial and superior ventricular wall with nodular encroachment on the ventricle, and one had a meningioma in the atrium of the right lateral ventricle.

Aged↗
PubMed1976

Treatment of experiment delayed cerebral arterial spasm with a beta2-adrenergic stimulator and a phosphodiesterase inhibitor.

Delayed cerebral arterial spasm was induced by subarachnoid hemorrhage in 11 rhesus monkeys. Ten monkeys (62%) developed spasm. Of seven monkeys treated with salbutamol (a beta2-adrenergic stimulating drug), five had relief of vasospasm. Four monkeys, one of which had failed to respond to salbutamol alone, were treated with salbutamol and aminophylline (a phosphodiesterase-inhibiting drug), and all four were relieved of their vasospasm. When considered as one group, the monkeys had an 81% response rate. The authors suggest that a combination of beta2-adrenergic stimulation and phosphodiesterase-inhibition might be of value in preventing or treating delayed cerebral arterial pressure.

Albuterol↗