PubMed Health⌕ Search

Biomedical subjects

C D Jones

Publications and source records attributed to C D Jones.

At least 91 records · Page 5Linked to original sources
PubMed2000

Composite dendritic cell neoplasm (NOS) and small lymphocytic lymphoma.

This report describes a composite (or "collision") of a dendritic cell neoplasm and small lymphocytic lymphoma. It represents the seventh example of dendritic cell neoplasia occurring in the setting of low-grade B-cell malignancy and the third example of a composite tumor, in which both neoplasms were present within the same lymph node. The small lymphocytic lymphoma component exhibited a typical CD20+, CD5+, and CD23+ immunophenotype. The dendritic cell neoplasm exhibited reactivity with CNA-42, but nonreactivity for CD21, CD35, smooth muscle actin, desmin, and epithelial membrane antigen (EMA). Equivocal cytoplasmic staining was seen for S100p, CD68, and Factor XIIIa. Ultrastructurally, the dendritic cell neoplasm exhibited desmosomes, rough endoplasmic reticulum, cytoplasmic intermediate filaments, and intercellular collagen. Because the immunophenotype and ultrastructure did not correspond to one of the five recognizable dendritic cell subtypes, the neoplasm was designated dendritic cell neoplasm, not otherwise specified (NOS). Polymerase chain reaction (PCR) analysis for immunoglobulin heavy chain gene rearrangements performed on individual components of the composite tumor demonstrated rearrangement within the small lymphocytic lymphoma component, but none in the dendritic cell component. The lack of an immunoglobulin heavy chain gene rearrangement within the dendritic cell component argues against a transformational event and supports the concept that these separate neoplasms represent a true "collision" or composite lesion.

Aged↗
PubMed1999

T-cell and antibody response characterisation of a new recombinant pre-S1, pre-S2 and SHBs antigen-containing hepatitis B vaccine; demonstration of superior anti-SHBs antibody induction in responder mice.

The incidence of non-responders to hepatitis B (HB) virus SHBs antigen (Ag) vaccines has prompted the development of pre-S containing vaccines. The aim of this study was to characterise the murine immune response to a novel recombinant particle (Hepagene) (Medeva plc) containing pre-S1, pre-S2 and SHBsAg components. Hepagene induced potent in vitro spleen T-cell proliferative responses in both BALB/c (maximum stimulation index (SI) = 38) and SWR/J (maximum SI = 43) strains of mouse, following immunisation. High concentrations of interferon-gamma and low concentrations of interleukin-10 were detected in the media of spleen cells stimulated with Hepagene. The anti-Hepagene antibody response was higher in SWR/J mice and alhydrogel adjuvant significantly improved the titres. Anti-pre-S1 antibody was detected in both strains of mouse, whereas antipre-S2 antibody was only detected in SWR/J mice. IgG subclass analysis of the anti-Hepagene response revealed a Th2-type response in BALB/c mice and a mixed Th1/Th2 response in SWR/J mice. Hepagene induced higher anti-SHBs antibody responses than Engerix-B (11097 and 1276 IU/ml, respectively) in BALB/c mice. Hepagene therefore, stimulates strong cellular and humoral immune responses in murine models. The high anti-SHBs antibody response suggests that Hepagene is an improved hepatitis B virus vaccine.

Amino Acid Sequence↗
PubMed1999

Accurate memory for colour but not pattern contrast in chicks.

The visual displays of animals and plants often look dramatic and colourful to us, but what information do they convey to their intended, non-human, audience [1] [2]? One possibility is that stimulus values are judged accurately - so, for example, a female might choose a suitor if he displays a specific colour [3]. Alternatively, as for human advertising, displays may attract attention without giving information, perhaps by exploiting innate preferences for bright colours or symmetry [2] [4] [5]. To address this issue experimentally, we investigated chicks' memories of visual patterns. Food was placed in patterned paper containers which, like seed pods or insect prey, must be manipulated to extract food and their patterns learnt. To establish what was learnt, birds were tested on familiar stimuli and on alternative stimuli of differing colour or contrast. For colour, birds selected the trained stimulus; for contrast, they preferred high contrast patterns over the familiar. These differing responses to colour and contrast show how separate components of display patterns could serve different roles, with colour being judged accurately whereas pattern contrast attracts attention.

Animals↗
PubMed1999

Colour vision of domestic chicks.

The colour vision of domestic chicks (Gallus gallus) was investigated by training them to small food containers decorated with tilings of grey and coloured rectangles. Chicks learn to recognise the colour quickly and accurately. Chicks have four types of single-cone photoreceptor sensitive to ultraviolet, short-, medium- or long-wavelength light. To establish how these receptors are used for colour vision, stimuli were designed to be distinguished only by specific combinations of receptors. We infer (1) that all four single cones are used, and (2) that their outputs are encoded by at least three opponency mechanisms: one comparing the outputs of ultraviolet- and short-wavelength-sensitive receptors, one comparing the outputs of medium- and long-wavelength receptors and a third comparing of the outputs of short- and long- and/or medium-wavelength receptors. Thus, the chicks have tetrachromatic colour vision. These experiments do not exclude a role for the fifth cone type, double cones, but other evidence suggests that these cones serve luminance-based tasks, such as motion detection, and not colour recognition.

Animals↗
PubMed1999

Population pharmacokinetics. A regulatory perspective.

The application of population approaches to drug development is recommended in several US Food and Drug Administration (FDA) guidance documents. Population pharmacokinetic (and pharmacodynamic) techniques enable identification of the sources of inter- and intra-individual variability that impinge upon drug safety and efficacy. This article briefly discusses the 2-stage approach to the estimation of population pharmacokinetic parameters, which requires serial multiple measurements on each participant, and comprehensively reviews the nonlinear mixed-effects modelling approach, which can be applied in situations where extensive sampling is not done on all or any of the participants. Certain preliminary information, such as the compartment model used in describing the pharmacokinetics of the drug, is required for a population pharmacokinetic study. The practical design considerations of the location of sampling times, number of samples/participants and the need to sample an individual more than once should be borne in mind. Simulation may be useful for choosing the study design that will best meet study objectives. The objectives of the population pharmacokinetic study can be secondary to the objectives of the primary clinical study (in which case an add-on population pharmacokinetic protocol may be needed) or primary (when a stand-alone protocol is required). Having protocols for population pharmacokinetic studies is an integral part of 'good pharmacometric practice'. Real-time data assembly and analysis permit an ongoing evaluation of site compliance with the study protocol and provide the opportunity to correct violations of study procedures. Adequate policies and procedures should be in place for study blind maintenance. Real-time data assembly creates the opportunity for detecting and correcting errors in concentration-time data, drug administration history and covariate data. Population pharmacokinetic analyses may be undertaken in 3 interwoven steps: exploratory data analysis, model development and model validation (i.e. predictive performance). Documentation for regulatory purposes should include a complete inventory of key runs in the analyses undertaken (with flow diagrams if possible), accompanied by articulation of objectives, assumptions and hypotheses. Use of diagnostic analyses of goodness of fit as evidence of reliability of results is advised. Finally, the use of stability testing or model validation may be warranted to support label claims. The opinions expressed in this article were revised by incorporating comments from various sources and published by the FDA as 'Guidance for Industry: Population Pharmacokinetics' (see the FDA home page http:/(/)www.fda.gov for further information).

Data Interpretation, Statistical↗
PubMed1999

Use of ultrasonography in the patient with acute renal trauma.

The purpose of this study was to assess the use of emergent ultrasonographic examination in acute traumatic renal injuries. Over a 3 year period, prospective data of all patients who had an emergency ultrasonogram were recorded. Thirty-two patients with 37 renal injuries were studied retrospectively to identify in how many patients the sonogram detected free fluid or a renal parenchymal abnormality. Free fluid in the abdomen was identified in 19 of 32 patients (59%). However, 12 of these 19 patients had concomitant injury, such as splenic rupture requiring splenectomy, severe liver lacerations, or bowel lacerations requiring repair, that were possible causes of the free fluid. Eliminating these patients, only seven of 20 patients with isolated renal injuries had free fluid in the abdomen (35%), whereas 13 of 20 patients (65%) had no evidence of free fluid. All seven patients with free fluid had moderate or severe renal injuries. Renal parenchymal abnormalities were identified on ultrasonograms in eight of 37 (22%) of injured kidneys. The abnormalities were detected more commonly in cases of severe injury (60%). In conclusion, acute injuries of the kidney from blunt abdominal trauma often are associated with significant splenic, hepatic, or bowel trauma. Isolated renal injuries frequently occur without the presence of free fluid in the abdomen. Furthermore, the ultrasonogram of the kidney often is normal with acute renal injuries, but it is more likely to be abnormal with severe (grade II or greater) renal injuries. Sonography may be used in the triage of patients with blunt abdominal trauma and possible renal injury. However, a negative ultrasonogram does not exclude renal injury, and, depending on clinical and laboratory findings, other imaging procedures such as computed tomography should be performed.

Abdominal Injuries↗
PubMed1999

Familial coagulation factor V deficiency caused by a novel 4 base pair insertion in the factor V gene: factor V Stanford.

An index patient with pseudohomozygosity for factor V Leiden was identified. Each of his two children inherited a different paternal factor V allele; a daughter was heterozygous for factor V Leiden, with 100% factor V activity, and a son was heterozygous for factor V deficiency, with 50% factor V activity. Genomic DNA was obtained from family members, and the 25 factor V exons and flanking intronic regions were sequenced in the proband and confirmed in the children. Within exon 13 of factor V, a 4 base insertion was found at NT 2856 in the proband and son. but not the daughter. This mutation, here designated factor V Stanford, results in a frameshift with loss of a thrombin activation site (R1545V) and premature termination of translation at amino acid 1560.

Alleles↗
PubMed1998

Increasing survival in AIDS patients with cytomegalovirus retinitis treated with combination antiretroviral therapy including HIV protease inhibitors.

OBJECTIVE: To assess the effect of combination antiretroviral therapy including HIV protease inhibitors on the survival of patients with cytomegalovirus retinitis (CMVR). DESIGN AND PARTICIPANTS: A longitudinal study of patients with CMVR diagnosed between October 1992 and May 1996 and followed to May 1997. SETTING: UK National Health Service specialist HIV medicine department. OUTCOME MEASURE: Time to death from first diagnosis of CMVR. Data were censored on 31 May 1997. RESULTS: Data were available on 147 patients with CMVR. Median survival of CMVR patients before December 1995 was 256 days [95% confidence interval (CI), 197-315]. Following the introduction of protease inhibitors in December 1995 this rose to 555 days (95% CI, 351-759). By 31 May 1996 median survival for the entire group of patients alive with CMVR had risen to 720 days (95% CI, 551-889). The mean survival after CMVR diagnosis was 224 days (n=89; 95% CI, 186-261; 1-year survival, 16%) in those who took no further antiretroviral therapy, 353 days in those who took nucleoside reverse transcriptase inhibitors but no protease inhibitors (n=34; 95% CI, 289-418; 1 -year survival, 50%), and 914 days in those who took a protease inhibitor (n=24; 95% CI, 768-1059; 1-year survival, 83%; P < 0.0001). Multivariate analysis showed that the strongest independent predictor of improved survival was having ever received a protease inhibitor after CMVR (relative risk of death, 0.063; 95% CI, 0.027-0.149; P < 0.0001). CONCLUSIONS: The use of HIV protease inhibitors in combination antiretroviral therapy has been associated with a marked increase in the survival of patients with CMVR.

AIDS-Related Opportunistic Infections↗
PubMed1998

Synthesis and antiviral activity of prodrugs of the nucleoside 1-[2',3'-dideoxy-3'-C-(hydroxymethyl)-beta-D-erythropentofuranosyl] cytosine.

The synthesis and antiviral evaluation of 21 prodrugs of 1-[2',3'-dideoxy-3'-C-(hydroxymethyl)-beta-D-erythropentofuranosyl ] cytosine 1 is reported. Cytosine N4-imine analogues were prepared by condensation of 1 with selected formamide dimethyl acetals. Amino acid substituted prodrugs were prepared from 1 or imine prodrug 2 by coupling with either N-tert-butoxycarbonyl (t-Boc)-L-valine or N-t-Boc-L- phenylalanine in the presence of dicyclohexycarbodiimide (DCC) and 4-dimethylaminopyridine (4-DMAP). Deprotection of the t-Boc protecting group was achieved with trifluoroacetic acid (TFAA) in methylene chloride. Cytosine N4-amide analogues were prepared by reaction of 1 with appropriate anhydrides in aqueous dioxane. Triacylated analogue 22 was prepared by reaction of 1 with four equivalents of benzoyl chloride in pyridine. Prodrugs were evaluated for activity against duck hepatitis B virus, herpes simplex virus types 1 and 2, human cytomegalovirus, and human immunodeficiency virus. A number of analogues were found comparable in activity to 1 with the cytosine N4-imine series more active than the amino acid substituted and cytosine N4-amide prodrugs. Slight to moderate cellular toxicity was observed with some analogues.

Antiviral Agents↗
PubMed1998

Estimation of the effect of increasing UVB exposure on the human immune system and related resistance to infectious diseases and tumours.

Exposure to UV light has, besides some beneficial effects (vitamin D production), many harmful effects on human health. UVB irradiation has been shown to suppress both systemic and local immune responses to a variety of antigens, including some microorganisms. However, it is still not known whether such immunomodulating effects may lead to an increase in the number and severity of certain tumours and/or infections in humans. We report herein the data provided by a project that was funded by the European Union (Programme Environment), and that was aimed at the estimation of the risk associated with increased UVB exposure due to ozone depletion regarding the deleterious effects on the immune system and related resistance to tumours and infections in humans. The data, obtained by the different research groups involved, were assembled and used to calculate for the first time a risk assessment for increased environmental exposure to UVB in human subjects.

Animals↗
PubMed1998

Characterization of the T- and B-cell immune response to a new recombinant pre-S1, pre-S2 and SHBs antigen containing hepatitis B vaccine (Hepagene); evidence for superior anti-SHBs antibody induction in responder mice.

Hepagene is a novel recombinant particle consisting of the pre-S1, pre-S2 and small surface (SHBs) antigens (Ag) of the hepatitis B virus (HBV) and is adjuvanted with alhydrogel in the final formulation. It has been primarily developed to enhance anti-SHBs antibody titres in inadequate responders, to conventional SHBsAg vaccines. Since non-compliance is also a problem with existing HBV vaccine schedules, the ability to accelerate current immunization regimens to provide more rapid protection has also been an important objective. Here we describe the T- and B-cell responses to Hepagene in two strains of responder mouse (BALB/c and SWR/J). Hepagene induced high in vitro spleen T-cell proliferative responses in both strains (max. Stimulation Index = 43), following intraperitoneal immunization. High concentrations of interferon-gamma (max. = 5000 pg/mL) were detected in the media of spleen cells cultured with non-adjuvanted Hepagene particles. SWR/J mice showed the highest serum antibody (Ab) titres to non-adjuvanted Hepagene. The presence of alhydrogel adjuvant in the vaccine formulation significantly improved the titres. Anti-pre-S1 Ab was detected in both strains of mouse but anti-pre-S2 Ab was only detected in the SWR/J strain. In BALB/c mice, the anti-Hepagene (non-adjuvanted) IgG1 Ab subclass was predominant but in SWR/J mice IgG1, IgG2a and IgG2b subclasses were of a similar magnitude. In BALB/c mice, Hepagene induced higher anti-SHBs Ab responses than Engerix-B (11097 IU/mL and 1276 IU/mL, respectively), following two doses of vaccine (10 micrograms/mouse). The vaccine therefore, induces strong cellular and humoral immune responses and these data suggest that Hepagene is an improved hepatitis B vaccine.

Animals↗
PubMed1998

The genetic basis of Drosophila sechellia's resistance to a host plant toxin.

Unlike its close relatives, Drosophila sechellia is resistant to the toxic effects of the fruit of its host plant, Morinda citrifolia. Using 15 genetic markers, I analyze the genetic basis of D. sechellia's resistance to this fruit's primary toxin, octanoic acid. D. sechellia's resistance is dominant in F1 hybrids between it and its sister species D. simulans. All chromosomes, except the Y and the dot fourth, carry genes affecting resistance. The third chromosome has the greatest effect and carries at least two factors. The X chromosome has an intermediate effect and harbors at least two genes, whereas the second chromosome carries at least one gene of weak effect. Thus, at least five loci are involved in this adaptation. However, I also identified large chromosome regions having no effect on resistance, suggesting that D. sechellia's resistance is neither very simple nor highly polygenic. Instead, resistance appears to have an oligogenic basis. D. sechellia's resistance to its host may contribute to ecological isolation between it and D. simulans.

Adaptation, Physiological↗
PubMed1997

Molecular determinants of tissue selectivity in estrogen receptor modulators.

Interaction of the estrogen receptor/ligand complex with a DNA estrogen response element is known to regulate gene transcription. In turn, specific conformations of the receptor-ligand complex have been postulated to influence unique subsets of estrogen-responsive genes resulting in differential modulation and, ultimately, tissue-selective outcomes. The estrogen receptor ligands raloxifene and tamoxifen have demonstrated such tissue-specific estrogen agonist/antagonist effects. Both agents antagonize the effects of estrogen on mammary tissue while mimicking the actions of estrogen on bone. However, tamoxifen induces significant stimulation of uterine tissue whereas raloxifene does not. We postulate that structural differences between raloxifene and tamoxifen may influence the conformations of their respective receptor/ligand complexes, thereby affecting which estrogen-responsive genes are modulated in various tissues. These structural differences are 4-fold: (A) the presence of phenolic hydroxyls, (B) different substituents on the basic amine, (C) incorporation of the stilbene moiety into a cyclic benzothiophene framework, and (D) the imposition of a carbonyl "hinge" between the basic amine-containing side chain and the olefin. A series of raloxifene analogs that separately exemplify each of these differences have been prepared and evaluated in a series of in vitro and in vivo assays. This strategy has resulted in the development of a pharmacophore model that attributes the differences in effects on the uterus between raloxifene and tamoxifen to a low-energy conformational preference imparting an orthogonal orientation of the basic side chain with respect to the stilbene plane. This three-dimensional array is dictated by a single carbon atom in the hinge region of raloxifene. These data indicate that differences in tissue selective actions among benzothiophene and triarylethylene estrogen receptor modulators can be ascribed to discrete ligand conformations.

Animals↗
PubMed1997

Localization of the prostatic apex for radiotherapy treatment planning using urethroscopy.

PURPOSE: To assess the ability of computed tomography (CT) scans and retrograde urethrograms to accurately define the prostatic apex in the craniocaudad dimension, using urethroscopy as a reference. METHODS AND MATERIALS: Plain film radiographs of the pelvis were obtained in 15 patients with early-stage adenocarcinoma of the prostate, with the tip of a urethroscope held in place at the external sphincter, which most closely approximates the prostatic apex. The scope was then withdrawn, and a retrograde urethrogram was performed. Immediately afterwards, a CT scan of the pelvis was obtained. Because differential filling of the bladder and rectum affects the position of the prostatic apex, patients voided prior to rather than in between the three consecutive studies. RESULTS: The urethroscopy-defined prostatic apex was located 4 +/- 8 mm (mean +/- SD) superior to the CT-defined apex, 13 +/- 3 mm (mean +/- SD) superior to the urethrogram tip and 30 +/- 7 mm (mean +/- SD) superior to the ischial tuberosities. There was significant interobserver variability in the location of the prostatic apex as determined by CT scans. Placement of the inferior border of the radiation portals at the ischial tuberosities would have resulted in irradiation of > or = 20 mm bulbar urethra, as defined by the dye column of the retrograde urethrogram, in 6 out of 15 (40%) of the patients and irradiation of < 10 mm bulbar urethra in 2 out of 15 (13%) of the patients. CONCLUSION: Because the prostate blends inferiorly with the urogenital diaphragm, CT scans do not allow one to precisely localize the prostatic apex. Due to anatomic variability, the ischial tuberosities do not allow one to accurately localize the prostatic apex. Retrograde urethrograms provide helpful supplemental information regarding the position of the prostatic apex for radiotherapy treatment planning.

Endoscopy↗
PubMed1997

Structure-activity relationships of selective estrogen receptor modulators: modifications to the 2-arylbenzothiophene core of raloxifene.

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

Adenocarcinoma↗