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Biomedical subjects

E Floyd

Publications and source records attributed to E Floyd.

At least 19 recordsLinked to original sources
PubMed2001

Tumor microvascular characterization using ultrasmall superparamagnetic iron oxide particles (USPIO) in an experimental breast cancer model.

The diagnostic potential of ultrasmall superparamagnetic iron oxide particles (USPIO) for quantitative tumor microvessel characterization was assessed by kinetic analysis of dynamic magnetic resonance imaging (MRI) in a rodent breast cancer model. Microvascular characteristics (transendothelial permeability (K(PS)) and fractional plasma volume (fPV)) were estimated in 32 female Sprague Dawley rats, bearing breast tumors of varying malignancy. These values were compared to a prototype macromolecular contrast medium standard, albumin-(GdDTPA)(30). Transendothelial permeability (K(PS)) correlated significantly (P < 0.05) with the tumor grade (Scarff-Bloom-Richardson (SBR) score) for the USPIO (r = 0.36), as well as for the reference macromolecule, albumin-(GdDTPA)(30) (r = 0.54). Estimates for the fPV did not show a statistically significant correlation with the tumor grade for either contrast medium. In conclusion, USPIO-enhanced MRI data were capable to characterize tumor microvessel properties in this breast cancer model: microvascular permeability (determined using USPIO) correlated significantly with tumor grade. Thus, quantitative estimation of microvascular characteristics in tumors could provide a surrogate of new vessel formation (angiogenesis) and thus a further important clinical indication for USPIO, in addition to MR angiography. J. Magn. Reson. Imaging 2001;13:882-888.

Albumins↗
PubMed2001

MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS-325) with correlations to histopathology.

A new contrast medium, MS-325, was compared to albumin-(Gd-DTPA)(30) in 18 chemically induced rat breast tumors based on quantitative estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) using a two-compartment bidirectional model. No significant correlation was found between MS-325-enhanced microvascular assays with either tumor grade or with microvascular counts (MVCs). In comparison, the correlation coefficient between K(PS) and histologic tumor grade using albumin-(Gd-DTPA)(30) (r =.58) was statistically significant (P <.01). Also, using albumin-(Gd-DTPA)(30), a significant correlation (r =.55, P <.05) was observed between the K(PS) and MVC, a biomarker of angiogenesis. Correlations between fPV and MVC were not statistically significant for either contrast medium. In conclusion, using MS-325, no significant correlations between the MR-estimated permeability values or plasma volumes were observed in experimental breast tumors with either the histologic tumor grade or MVC. This analysis confirms our previous determination that capillary permeability estimates, using a prototype large molecular contrast medium, albumin-(Gd-DTPA)(30), correlate significantly with both histologic tumor grade and MVC.

Animals↗
PubMed2001

Assessment of a rapid clearance blood pool MR contrast medium (P792) for assays of microvascular characteristics in experimental breast tumors with correlations to histopathology.

The diagnostic potential of a new rapid clearance blood pool contrast medium (P792; MW = 6.47 kDa) for the MR assessment of microvessel characteristics was assessed in 42 chemically-induced breast tumors, with comparisons to albumin-(Gd-DTPA). Microvessel characteristics, including the transendothelial permeability (K(PS)) and the fractional blood volume (fPV), were estimated by using dynamic MR data fit to a bidirectional two-compartment model. The MR-derived estimates for K(PS) and fPV using each contrast agent were compared, and assays using each contrast agent were correlated to the histologic tumor grade (SBR score) and the microvascular density (MVD) counts. Using P792-enhanced data, neither K(PS) nor fPV showed a statistically significant correlation with the tumor grade or the MVD (P >.05). Conversely, using albumin-(GdDTPA)(30), K(PS) values correlated significantly with the histologic tumor grade (r =.55; P <.0005) and the MVD (r =.34, P <.05), whereas no correlation was established for fPV. In conclusion, based on P792 data no correlation between tumor microvascular characteristics and histologic markers (SBR score or MVD) was found in this breast tumor model. Our analysis suggests that contrast media of relatively large (on the order of 90 kDa) molecular size, such as albumin-(GdDTPA)(30), are more accurate for the characterization of tumor microvessels.

Animals↗
PubMed2001

The anti-tumor activity of anti-CTLA-4 is mediated through its induction of IFN gamma.

The T-cell-specific receptor, CTLA-4, has been demonstrated to be a potent negative regulator of lymphocyte activation, the functional significance of which has been demonstrated in murine tumor models using blocking antibodies. However, the mechanism(s) involved in enhancing tumor regression has not been identified. In this study, we determined whether IFN gamma was playing a role in this activity. In vitro, anti-CTLA-4 enhanced IFN gamma production by lymph node cells obtained from tumor-bearing mice (351 pg/ml vs 77 pg/ml). Additionally, fibrosarcoma-challenged animals treated with anti-CTLA-4 had elevated levels of the IFN-inducible enzyme 2-5-OAS in draining lymph nodes (850 pM vs 260 pM for controls) and an increased amount of IFN gamma in tumor lysates (at day 7, 620 pg/100 micrograms vs 160 pg/100 micrograms in controls). The importance of IFN gamma was demonstrated by the ability of neutralizing antibodies to completely abrogate the anti-tumor effects of anti-CTLA-4. Moreover, fibrosarcoma cells were shown to be exquisitely sensitive to IFN gamma-mediated class I upregulation and histological examination of tumors from anti-CTLA-4-treated mice revealed a trend toward increased tumor cell apoptosis and decreased angiogenesis. These studies have demonstrated that one mechanism for the anti-tumor effects of anti-CTLA-4 relates to its ability to augment IFN gamma production, resulting in an increased expression of class I on the tumor, enhanced apoptosis, and a decrease in blood vessel growth.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation.

PURPOSE: To define the diagnostic potential of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles for the quantitative characterization of tumor microvasculature. MATERIALS AND METHODS: NC100150 injection, a USPIO in clinical trials, and albumin-(Gd-DTPA)(30) were compared at MR imaging on sequential days in the same 19 rats with mammary tumors. Kinetic analysis of dynamic T1-weighted three-dimensional spoiled gradient-recalled imaging data with a two-compartment bidirectional model yielded MR imaging estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) for each contrast medium. RESULTS: Strongly positive and significant correlations were observed between MR imaging-derived K(PS )estimates and histologic tumor grade with either the soluble albumin-(Gd-DTPA)(30) (r = 0.88; P <.001) or larger particulate USPIO (r = 0.82; P <.001). A significant correlation (P <.05) was observed with each contrast medium between K(PS) and the histologic microvascular density (MVD), an angiogenesis indicator. Despite the considerable difference in molecule and particle sizes, no significant difference was observed in the MR imaging-derived mean permeability values generated with the two contrast media. CONCLUSION: USPIO, a macromolecular particulate MR imaging contrast agent, can be applied successfully to characterize tumor microvessels in animals. USPIO-derived K(PS) correlated strongly with histopathologic tumor grade, MVD, and K(PS) values derived by using albumin-(Gd-DTPA)(30) in the same tumors.

Animals↗
PubMed1998

Practices that minimize trauma to the genital tract in childbirth: a systematic review of the literature.

BACKGROUND: Trauma to the genital tract commonly occurs at birth, and can cause short- and long-term morbidity. Clinical measures to reduce its occurrence have not been fully identified. METHODS: A systematic review of the English language literature was conducted to describe the current state of knowledge on reduction of genital tract trauma before planning a large randomized controlled trial of ways to prevent such trauma. Randomized trials and other published reports were identified from relevant databases and hand searches. Studies were reviewed and assessed using a structured format. RESULTS: A total of 77 papers and chapters were identified and placed into 5 categories after critical review: 25 randomized trials, 4 meta-analyses, 4 prospective studies, 36 retrospective studies, and 8 descriptions of practice from textbooks. The available evidence is conclusive in favor of restricted use of episiotomy. The contribution of maternal characteristics and attitudes to intact perineum has not been investigated. Several other topics warrant further study, including maternal position, style of pushing, and antenatal perineal massage. Strong opinions and sparse data exist regarding the role of hand maneuvers by the birth attendant for perineal management and birth of the baby. This became the topic of the planned randomized controlled trial, which was completed; results will be published soon. CONCLUSIONS: The case for restricting the use of episiotomy is conclusive. Several other clinical factors warrant investigation, including the role of hand maneuvers by the birth attendant in preventing birth trauma. A large randomized controlled trial will report on this topic.

Delivery, Obstetric↗
PubMed1992

Temporal lymphoreticular changes caused by ts1, a paralytogenic mutant of Moloney murine leukemia virus TB.

Inoculation of newborn FVB/N mice with ts1, a mutant of Moloney murine leukemia virus TB, induced severe thymic atrophy, spongiform polioencephalomyelopathy, and fatal posterior paralysis of the affected mice 35-40 days after inoculation. During the early course of infection viral replication was found in the spleen and, more importantly, within the thymus. Of these organs, the thymus was affected most severely by ts1-infection. Thymic weights of infected mice decreased markedly during disease progression, culminating in severe atrophy at the time of paralysis. During the first 10 days after inoculation, the virus replicated within the endothelial lining of splenic and thymic capillaries and was released albuminally into the basement membrane before spreading outwardly into perithelial, epithelial, and reticuloendothelial cells. Within these cells there was productive viral replication and subsequent dissemination of the virus to the thymic T cell population. Early infection (up to 10 days after inoculation) of the thymus induced an increase in thymocytic mitosis, followed by a progressive increase in thymocytic death between 15 and 35 days after inoculation. Thymuses from paralyzed mice killed 30-39 days after inoculation, demonstrated pronounced involution, characterized by loss of lobular architecture, effacement of the cortex and medulla, severe depletion of thymocytes, and partial or complete loss of Hassall's corpuscles. Immunohistochemistry for viral antigens showed positive labeling of splenic megakaryocytes, reticuloendothelial cells, and thymocytes in mitosis, and reticulo-epithelial-endothelial cells of the thymus. The thymic phase of viral replication appeared to be crucial for development of neurological lesions and posterior paralysis.

Animals↗
PubMed1991

Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB.

The ts1 mutant of Moloney murine leukemia virus TB causes degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. To investigate the pathogenesis of the thymic atrophy caused by ts1, we constructed a chimeric virus, ts1-Cas(NS), in which a major portion of the U3 region of the long terminal repeat of ts1, a T-lymphotropic and neurovirulent murine leukemia virus, was replaced by the corresponding U3 region of Cas-Br-E, a B-lymphotropic and neurovirulent murine leukemia virus. In FVB/N mice, ts1-Cas(NS) induced paralytic and wasting disease with incidence, severity, and latency similar to that induced by ts1, but it failed to cause thymic atrophy as severe as that observed in ts1-infected mice. Furthermore, thymocytes cultured from ts1-Cas(NS)-infected mice died at a much slower rate than those of ts1-infected mice. The U3 substitution in ts1-Cas(NS) specifically diminished the ability of the virus to replicate in the thymus, whereas viral replication in the spinal cord was not significantly affected; thus, neurovirulence was not changed. The correlation of reduced thymic atrophy with decreased thymic viral titers and the decreased ability of ts1-Cas(NS) to cause thymocyte death in mice suggest strongly that the marked thymic atrophy in ts1-infected mice is not an indirect effect occurring secondary to neurodegenerative and wasting disease but is a direct cytopathic effect of high-level viral replication in the thymus.

Animals↗
PubMed1991

Toxoplasmosis in two cats with inflammatory intestinal disease.

Lymphocytic-plasmacytic enteritis, a chronic inflammatory intestinal disease, was diagnosed in 2 cats. In 1 cat, recurrence of clinical signs after initiating treatment was attributed to relapse of the inflammatory intestinal disease, but was found to be attributable to relapsing toxoplasmosis secondary to immunosuppressive drug therapy. Treatment with clindamycin resolved the recurrent toxoplasmosis. In the second cat, clinical signs of toxoplasmosis did not develop, but serologic testing yielded evidence of active toxoplasmosis. Treatment with clindamycin caused the titers to decrease. Relapsing toxoplasmosis may be responsible for apparent resistance to treatment in cats for inflammatory intestinal disease being treated with immunosuppressive drugs.

Animals↗
PubMed1991

Panfibrinonecrotic colitis in a dog treated by subtotal colectomy.

A dog with signs of small intestinal disease developed signs of severe large intestinal disease after being treated with multiple agents. Endoscopy and biopsy revealed total destruction of the colonic mucosa, which necessitated total parenteral nutrition plus subtotal colectomy. It was hypothesized that the multiple prior treatments led to an overgrowth of toxigenic or cytotoxic bacteria, which caused this colonic mucosal destruction.

Animals↗
PubMed1991

High susceptibility of FVB/N mice to the paralytic disease induced by ts1, a mutant of Moloney murine leukemia virus TB.

The ts1 mutant of Moloney murine leukemia virus TB causes a degenerative neurologic and immunologic disease in susceptible strains of mice. This disease syndrome is characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, generalized bodywasting, and marked thymic atrophy associated with immune deficiency. The viral genetic determinants responsible for hindlimb paralysis in BALB/c and CFW/D mice have been localized to two point mutations in the env gene: one results in a Val-25----IIe substitution in the envelope precursor polyprotein gPr80env and the other, in an Arg-430----Lys substitution in the gp70. In this report we present studies showing that FVB/N mice were highly susceptible to ts1 and exhibited the shortest and most uniform latency period of all the murine strains tested. In addition, we have found that, unlike in CFW/D and BALB/c mice, only the Val-25----IIe substitution in the gPr80env is required to induce hindlimb paralysis in FVB/N mice. Our studies show that there was enhanced replication of ts1 in all tissues of FVB/N mice and that the virus titer in the spinal cord was more than 10-fold higher in FVB/N than in BALB/c mice by 30 days postinoculation, when the clinical signs of paralysis became evident in FVB/N mice. Apparently, other host factors that do not require the Arg-430----Lys substitution allowed high levels of viral replication within the central nervous system of FVB/N mice. These results, together with the finding that 100% of FVB/N mice that were inoculated with ts1 at 5 days of age developed hindlimb paralysis at 30-60 days postinoculation, whereas only 33% of 5-day-old BALB/c mice developed hindlimb paralysis with a much longer latency period, suggest that subtle virus-host interactions determine the incidence, the latency period, and the severity of the disease caused by ts1.

Aging↗
PubMed1990

Site-directed mutagenesis of the codon for Ile-25 in gPr80env alters the neurovirulence of ts1, a mutant of Moloney murine leukemia virus TB.

ts1, a spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB, causes hind-limb paralysis in mice. A Val-25----Ile substitution in gPr80env is responsible for temperature sensitivity, inefficient processing of gPr80env, and neurovirulence. In this study, the Ile-25 in gPr80env was replaced with Thr, Ala, Leu, Gly, and Glu by site-directed mutagenesis of the codon for Ile-25 to generate a new set of mutant viruses, i.e., ts1-T, -A, -L, -G, and -E, respectively. The phenotypic characteristics of these mutant viruses differed from those of ts1. For each mutant, the degree of temperature sensitivity was correlated with the degree of inefficient processing of gPr80env, and the following rank order was observed for both parameters: ts1-E greater than ts1-G greater than ts1-L greater than ts1-A greater than ts1 greater than ts1-T. In FVB/N mice, mutant viruses of low and intermediate temperature sensitivity and inefficiency in processing of gPr80env were neurovirulent and consistently caused mutant-specific disease profiles: ts1-T caused severe whole-body tremor, ts1-A generally caused hind-limb paralysis, and ts1-L generally caused a delayed-onset paraparesis. By 150 days postinfection, FVB/N mice that were infected with ts1-G and -E, mutants of high temperature sensitivity and inefficiency in processing of gPr80env, had lymphoid leukemia instead of a neurological disease. These results suggest that the dynamics of gPr80env processing are important in determining the neurovirulent phenotype in vivo.

Animals↗
PubMed1984

Nonspecific cytotoxic cells in fish (Ictalurus punctatus). III. Biophysical and biochemical properties affecting cytolysis.

Nonspecific cytotoxic cells (NCC) from the catfish (Ictalurus punctatus) may comprise a population of cells that are responsible for cellular immunity in the fish. NCC kill a wide variety of transformed target cells, and previous studies have indicated that NCC share properties with mammalian natural killer cells. In the present study, many biophysical and biochemical properties of NCC were defined. NCC were nylon wool nonadherent and adherent. NCC activity was also enriched in plastic nonadherent cells. NCC were nonphagocytic (for carbonyl iron), and they did not bind to Sephadex G-10. Characterization of NCC by density gradient centrifugation indicated that they comprise a relatively homogenous population of cytolytic cells that band at 45.5% Percoll. Moderate to high doses (500-2500 R) of X-irradiation produced a stimulatory effect on NCC lysis of labeled target cells. Additional studies indicated that a soluble suppressor protein in catfish serum (CFS) regulated NCC activity. This S. aureus protein A binding component isolated from CFS suppressed NCC activity. Analysis by SDS-PAGE indicated that the soluble regulatory protein had properties similar to immunoglobulin. These data indicate that NCC share some biophysical properties with mammalian natural killer cells. In addition, NCC appear to be under partial cell regulation by a radiation sensitive suppressor cell and also by a soluble regulator serum immunoglobulin component.

Animals↗
PubMed1984

Dialyzable leukocyte extracts contain thymosin.

Trypsinization of human T-lymphocytes removes surface receptors which bind to sheep erythrocytes (E). Human dialyzable leukocytes extracts (DLE) and thymosin (Fraction V) have been shown to significantly increase the rate of regeneration of T-lymphocyte E-receptors. Both physical-chemical and immunochemical results reported herein indicate that the enhancing effect of human DLE preparations on the rate of regeneration of T-lymphocyte E-receptors is due at least in part to the presence of thymosin alpha 1-peptide in these preparations. Thymosin alpha 1-peptide purified from thymosin Fraction V and putative thymosin alpha 1 preparations purified from human DLEs were each active not only in increasing the rate of regeneration of T-lymphocyte E-receptors removed by trypsinization but also were active in vitro in markedly increasing the number of E-rosetting cells in two patients with immunodeficiency disease manifested in part as a reduction in the normal percentage of mature T-lymphocytes capable of forming E-rosettes.

Cross Reactions↗
PubMed1981

Cystic fibrosis ciliary dyskinesia substances and pulmonary disease. Effects of ciliary dyskinesia substances on neutrophil movement in vitro.

Cultured mononuclear cells (MNC) from individuals homozygous or heterozygous for the defective gene causing the inherited disease cystic fibrosis (CF) synthesize three unusual "mediators" termed ciliary dyskinesia substances (CDS), which markedly affect tracheal mucociliary systems in vitro. MNC cultures from normal healthy controls do not accumulate any CDS, whereas MNC cultures from non-CF patients controls with pulmonary disease synthesized at least one CDS. The possible involvement of the CDS in pulmonary disease is being investigated. In this study, we sought to determine whether the CDS could be chemoattractants for polymorphonuclear neutrophils (PMN), since they have characteristics in common with known chemoattractants generated by alveolar macrophages. Our analyses of crude MNC culture supernates indicated that cultures from both CF genotypes accumulate significantly higher levels of PMN chemoattractants than do analogous cultures from normal healthy controls. CF homozygote MNC also generated more activity than MNC from patient controls with chronic pulmonary disease. Fractionation of MNC culture supernates by gel permeation chromatography and characterization of active fractions demonstrated six distinct PMN chemoattractants in cultures from CF genotypes; five were also present in patient control and four in normal healthy control cultures. The excessive chemoattractant activity in MNC cultures from CF genotypes and patient controls was due to several different substances produced by monocytes: (a) two components of 1,000-3,500 mol wt. (b) two fragments of C5, and (c) a fragment of C3. One C5 fragment had ciliary dyskinesia activity, the other did not. The C3 fragment chemoattractant also had ciliary dyskinesia activity and was not found in MNC cultures from patient controls. A third CDS, Which is CF-specific (5,000 mol wt), was neither chemotactic not chemokinetic and did not inhibit random PMN migration; however, fractions containing this CF-specific CDS completely inhibited PMN chemotaxis in response to three different chemoattractants. We conclude that all of the CDS can potentially play a role in the pathophysiology of lung disease, as judged by their effects on PMN movement in vitro.

Biological Assay↗