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PubMed2003

Patterns of gene expression in peripheral blood mononuclear cells of rhesus macaques infected with SIVmac251 and exhibiting differential rates of disease progression.

Using the Affymetrix HuGeneFL GeneChip, the global expression patterns of genes in the peripheral blood mononuclear cells (PBMCs) of rhesus macaques, infected with SIVmac251 and exhibiting rapid, typical, or slow rates of disease progression, were examined. Assessments of the change in gene expression (fold change), the temporal coordination of gene expression (self-organizing map analysis), and the similarities and significant differences in gene expression across the groups were performed on samples taken before infection and 3 and 7 weeks postinfection. An upregulation of the p27 interferon-inducible gene and of genes associated with cellular activation and immune response was observed in all three groups. Rapidly progressing animals exhibited a modest number of genes with a change in expression of 3-fold or greater, typically progressing animals exhibited the greatest number, and slowly progressing animals exhibited the fewest. Self-organizing map cluster analysis indicated that rapidly progressing animals exhibited the least coordinated gene expression over the three study time points, typically progressing animals exhibited a moderate degree, and animals with slow progression exhibited the most coordinated gene expression. Mann-Whitney U analysis indicated that differences in gene expression were most pronounced between the rapidly and slowly progressing groups and least pronounced between the rapidly and typically progressing animals. These observations elucidate distinct features of gene expression in animals with different rates of disease progression.

Animals↗

PubMed1996

Liposomal bupivacaine. Extended duration nerve blockade using large unilamellar vesicles that exhibit a proton gradient.

BACKGROUND: There is a clinical requirement for longer-acting local anesthetics, particularly for the management of post-operative and chronic pain. In this regard, liposomes have been suggested to represent a potentially useful vehicle for sustained drug release after local administration. In the current study, the authors used a transmembrane pH gradient to efficiently encapsulate bupivacaine within large unilamellar vesicles. They report on the kinetics of drug uptake and release and the duration of nerve blockade. METHODS: The rate and extent of bupivacaine uptake into large unilamellar vesicles that exhibit a pH gradient (interior acidic) were determined and compared to drug association with control liposomes that did not exhibit a proton gradient. In subsequent studies, researchers examined the kinetics of bupivacaine release from these liposome systems in vitro. Using the guinea pig cutaneous wheal model, the rate of clearance of the liposome carrier was monitored after intradermal administration, using a radiolabelled lipid marker, and the duration of nerve blockade produced by free and liposomal bupivacaine was compared. RESULTS: Bupivacaine was rapidly and efficiently accumulated within liposomes that exhibited a pH gradient (interior acidic) with trapping efficiencies of 64-82% of total drug, depending on the initial bupivacaine:phospholipid ratio. Little uptake was seen, however, for control vesicles that did not exhibit a transmembrane proton gradient. Using an in vitro model of drug clearance, liposomally encapsulated bupivacaine was found to be slowly released for a longer period of time compared with either the free drug or bupivacaine associated with control (no pH gradient liposomes). In the guinea pig cutaneous wheal model, more than 85% of the liposomal carrier was found to remain at the site of administration for 2 days. The sustained drug release afforded by liposomes that exhibited a pH gradient resulted in an increase in the duration of nerve blockade of as much as threefold compared with either the free drug or bupivacaine in the presence of control (no pH gradient) liposomes. Recovery of half maximal response (R2.5) after administration of 0.75% free bupivacaine, for example, was approximately 2 h, whereas the same dose of bupivacaine in pH gradient liposomes exhibited a R2.5 of approximately 6.5 h. CONCLUSIONS: Large unilamellar vesicles that exhibit a pH gradient can efficiently encapsulate bupivacaine and subsequently provide a sustained-release system that greatly increases the duration of neural blockade.

Anesthetics, Local↗

PubMed2001

Exhibits facilitate histology laboratory instruction: student evaluation of learning resources.

Some professional schools have replaced microscopes for histology laboratory instruction with printed and electronic media. It is recognized that these media cannot replace experience with the microscope and that there is a cognitive dissonance of completely replacing microscope study. In addition, students believe that their time is not optimally used in the traditional histology laboratory. Therefore, at Loma Linda University, nine weekly microscope exhibits consisting of 10-15 slides each were prepared. For each exhibited slide, a one page "atlas" is provided, consisting of labeled low- and high-power color micrographs taken from that slide and an informative legend. By referring to the atlas, the student can easily identify the exact field and the labeled features with little help from an instructor. A live or taped video demonstration of the microscope exhibit is available on the first day of the exhibit. During the eighth week of the quarter, students were asked to evaluate the various learning resources available to them. No resource was valued significantly more than the microscope exhibits, but the video demonstrations were valued significantly more than the printed black and white atlas or the color atlas on CD. These exhibits have been used for 2 years to instruct a class of 90 dental students. Advantages are (1) students' time is used efficiently, (2) only one slide set and a fourth as many microscopes need be maintained compared with a traditional laboratory, and (3) one-of-a-kind slides derived from research activities provide for high impact learning.

Computer-Assisted Instruction↗

PubMed2001

Computerized scientific exhibit utilization: observations from infoRAD at the radiologic society of North America Scientific Assembly.

No publication has discussed utilization of computer scientific exhibits (CSE) at national symposia, despite their growing numbers. The hypothesis of this project was that, when given a choice, viewers initially would prefer a more conventional paper presentation of a scientific exhibit over that of an electronic presentation. A nearly identical paper version of the introductory screen to an infoRAD CSE was placed adjacent to the workstation. Utilization of the paper introduction, computer introduction, and both, as well as subsequent behavior, was recorded. Of 67 visitors, initial user choice was 56.7% paper and 43.3% computer. Over the entire time at the exhibit 25.4% only looked at the handout, 25.4% only at the computer, and 49.3% perused both. Only 10.5% completed the entire exhibit, and 0.94% of total registrants visited the CSE. Overall, 74.7% perused the CSE when leaving the exhibit area. Upon arrival, viewers preferred the more conventional paper presentation, confirming the project hypothesis. Surprisingly, about 75% eventually perused at least a portion of the computer presentation. Although a small fraction of Radiologic Society of North America (RSNA) registrants visited the CSE, the findings presented are promising and suggest that CSE presence at national meetings is justifiable, providing a "first step" toward CME outcomes analysis of CSE. Overall, these findings are promising and suggest that computer scientific exhibit presence at national meetings is justifiable.

Audiovisual Aids↗

PubMed1997

[Is it allowed to have a public open exhibition of human plastinated specimens in Japan?].

This survey was conducted to know what inhibits the public open exhibitions of human anatomical specimens. Questionnaires were handed to 1,035 visitors to the public open exhibition of plastinated specimens at the University of Tokyo between March 30 and April 4, 1995. Five hundred and twenty-two responses were analyzed. The survey revealed following responses of medial and non-medical visitors. 1) Over 90 percent of the visitors welcomed to the public open exhibition of human anatomical specimens. 2) Visitors concerned about the aim of the exhibition and hoped explanations of exhibited specimens. They thought it is necessary to pay attention to the privacy of the cadavers and their families. 3) The most impressive specimens to the visitors were whole body silicone specimens and a series of slices of a whole body for both medical and non-medical visitors. 4) Medical visitors evaluated specimens high for medical education to understand three dimensional structures. On the contrary, non-medical visitors are astonished to encounter the whole body specimens not the dissected ones, and found the identity and human beings in the specimens. 5) Some anatomists strongly stand against the public open exhibitions of anatomical specimens because the plastinated specimens are quite different from ordinary hormaline fixed specimens and they expect that non-medical people must get upset about the specimens.

Anatomy↗

PubMed1999

Localization of NADPHd-exhibiting neurons in the spinal cord of the rabbit.

Segmental and laminar distributions of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting neurons were examined in the rabbit spinal cord by using horizontal, sagittal, and transverse sections. A large number of NADPHd-positive neurons in the spinal cord of rabbit appeared to fall into six categories (N1-N6), but others could not be classified. Major cell groups of NADPHd-exhibiting neurons were identified in the superficial dorsal horn and around the central canal at all spinal levels and in the intermediolateral cell column at thoracic and upper lumbar levels. NADPHd-exhibiting neurons of the pericentral region were divided into a thin subependymal cell column containing longitudinally arranged, small bipolar neurons with processes penetrating deeply into the intermediolateral cell column and/or running rostrocaudally in the subependymal layer. The second pericentral cell column located more laterally in lamina X contains large, intensely stained NADPHd-exhibiting neurons with long dendrites radiating in the transverse plane. In the pericentral region (lamina X), close association of NADPHd-exhibiting somata and fibers and mostly longitudinally oriented blood vessels were detected. Neurons of the sacral parasympathetic nucleus, seen in segments S1-S3, exhibited prominent NADPHd cellular staining accompanied by heavily stained fibers extending from Lissauer's tract through lamina I along the lateral edge of the dorsal horn to lamina V. A massive dorsal gray commissure, highly positive in NADPHd staining, was found in segments S1-S3. Scattered positive cells were also found in the deeper dorsal horn, ventral horn, and white matter. Fiberlike NADPHd staining was found in the superficial dorsal horn and pericentral region in all the segments studied. Dense, punctate, nonsomatic NADPHd staining was detected in the superficial dorsal horn, in the pericentral region all along the rostrocaudal axis, and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments Th2-L2), Onuf's nucleus (segments S1-S3), and the dorsal part of the dorsal gray commissure (S1-S3).

Animals↗

PubMed2005

Higher magnitude accumbal phasic firing changes among core neurons exhibiting tonic firing increases during cocaine self-administration.

Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in the firing rate of nucleus accumbens neurons within seconds of cocaine-reinforced lever presses, as well as changes that occur over the course of the cocaine self-administration experiment, i.e. tonic changes in firing rate. During the self-administration period of the experiment, individual neurons exhibit either a tonic increase, a tonic decrease, or no tonic change in firing rate, relative to the neuron's firing rate during the pre-drug period. We evaluated whether rapid-phasic changes in firing were differentially associated with tonically reduced or tonically elevated firing of nucleus accumbens core and shell neurons in cocaine self-administering rats. Rapid-phasic firing patterns within seconds of the cocaine-reinforced lever press were exhibited predominantly by core neurons that also exhibited tonic increases in firing. Conversely, core neurons that did not exhibit such rapid-phasic firing patterns were more likely to show tonically reduced firing. Moreover, core neurons were more likely than shell neurons to exhibit: 1) tonic increases in firing and 2) rapid-phasic increases in firing preceding the cocaine-reinforced lever press. These differences between accumbens subterritories may be related to their distinct involvement in operant responding; the present findings are consistent with an emerging literature which implicates shell in contextual stimulus-induced responding, and core in processing the instrumental response via its discrete output to classic basal ganglia structures. The distinct tendency of the core to exhibit increased firing, coupled with its dichotomous firing outputs (i.e. tonic decreases without rapid phasic responses or tonic increases with rapid phasic responses), may reflect particular sensitivity of these neurons to excitatory limbic afferent signaling involved in instrumental responding. Enhanced phasic responsivity in the core may be an integral component of the mechanism inherent in normal reward processing which is subverted by chronic drug exposure.

Animals↗

PubMed1998

Periaqueductal gray neurons exhibit increased responsiveness associated with audiogenic seizures in the genetically epilepsy-prone rat.

The ventrolateral periaqueductal gray is implicated as a component of the neuronal network for audiogenic seizure. This implication is based on immunocytochemical labeling of the proto-oncogene, c-fos, and microinjection studies in the severe substrain of genetically epilepsy-prone rats that exhibits tonic seizures. The present study examines changes in acoustically evoked neuronal responses within the periaqueductal gray in the awake and behaving genetically epilepsy-prone rat as compared to normal Sprague Dawley rats. Two populations of neuronal response were observed in the periaqueductal gray of both genetically epilepsy-prone and normal rats. Most of the neurons exhibited long latencies (>10 ms) and lower thresholds, and were more responsive to the acoustic stimulus. The remainder of the periaqueductal gray neurons exhibited short latencies (<10 ms) and higher thresholds, and exhibited minimal responsiveness to the acoustic stimulus. The mean threshold of periaqueductal gray acoustically evoked neuronal firing of short-latency neurons was significantly higher than normal in the genetically epilepsy-prone rat. The number of acoustically evoked action potentials was significantly elevated in the genetically epilepsy-prone rat, particularly at the highest acoustic intensity and at a repetition rate of 1/2 s. In the genetically epilepsy-prone rat, the number of action potentials exhibited adaptation (habituation) at 1/s as compared to 1/2 s across stimulus intensities. Habituation in normal rats was observed primarily at high intensities (95 dB sound pressure level or above). During wild running and tonic seizures in the genetically epilepsy-prone rat, periaqueductal gray neurons. which had diminished firing rates due to habituation, exhibited a tonic firing pattern. Just (1-5 s) prior to the onset of tonic convulsive behaviors, an increase in the rate of periaqueductal gray tonic firing was observed. These patterns of abnormal neuronal firing suggest that periaqueductal gray neurons may be involved in generation of the tonic seizure behavioral component of audiogenic seizure in the genetically epilepsy-prone rat, which will need confirmation in other audiogenic seizure models.

Acoustic Stimulation↗

PubMedDate not supplied

Paracoccidioides brasilienses isolates obtained from patients with acute and chronic disease exhibit morphological differences after animal passage.

The basis for virulence in Paracoccidioides brasiliensis is not completely understood. There is a consensus that the sequential in vitro subcultivation of P. brasiliensis leads to loss of its pathogenicity, which can be reverted by reisolation from animal passage. Attention to morphological and biochemical properties that are regained or demonstrated after animal passage may provide new insights into factors related to the pathogenicity and virulence of P. brasiliensis. We evaluated morphological characters: the percentage of budding cells, number of buds by cell and the diameter of 100 mother cells of yeast-like cells of 30 P. brasiliensis isolates, before and after animal passage. The isolates were obtained from patients with different clinical forms of paracoccidioidomycosis (PCM): acute form (group A, n=15) and chronic form (group C, n=15). The measurement of the yeast cell sizes was carried out with the aid of an Olympus CBB microscope coupled with a micrometer disc. We measured the major transverse and longitudinal axes of 100 viable cells of each preparation. The percentage of budding cells as also the number of buds by cell was not influenced by animal passage, regardless of the source of the strain (acute or chronic groups). The size values of P. brasiliensis isolates from groups A and C, measured before the animal passage exhibited the same behavior. After animal passage, there was a statistically significant difference between the cell sizes of P. brasiliensis isolates recovered from testicles inoculated with strains from groups A and C. The maximum diameter of mother cells from group A isolates exhibited a size of 42.1 microm in contrast with 32.9 microm exhibited by mother cells from group C (p<0.05). The diameter of 1500 mother cells from group A isolates exhibited a medium size of 16.0 microm (SD +/- 4.0), a value significantly higher than the 14.1 microm (SD = +/- 3.3) exhibited by 1500 mother cells from group C isolates (p<0.05). Our results reinforce the polymorphism exhibited by P. brasiliensis in biological material and the need for further investigations to elucidate the role of morphological parameters of the fungus in the natural history of the disease.

Acute Disease↗

PubMed2004

Reports of zoonotic disease outbreaks associated with animal exhibits and availability of recommendations for preventing zoonotic disease transmission from animals to people in such settings.

OBJECTIVE: To assess the number of zoonotic disease outbreaks associated with animal exhibits and identify published recommendations for preventing zoonotic disease transmission from animals to people in exhibit settings. DESIGN: Literature review and survey of state public health veterinarians and state epidemiologists. PROCEDURE: MEDLINE and agriculture databases were searched from 1966 through 2000. Retrieved references and additional resources provided by the authors were reviewed. A survey was sent to state public health veterinarians and state epidemiologists to determine whether their states had written recommendations or guidelines for controlling zoonotic diseases in animal exhibition venues, whether their states maintained a listing of animal exhibitors in the state, and whether they had any information on recent outbreaks involving animals in exhibitions. RESULTS: 11 published outbreaks were identified. These outbreaks occurred in a variety of settings including petting zoos, farms, and a zoological park. An additional episode involving exposure to a potentially rabid bear required extensive public health resources. A survey of state public health veterinarians identified 16 additional unpublished outbreaks or incidents. Most states did not have written recommendations or guidelines for controlling zoonotic diseases or any means to disseminate educational materials to animal exhibitors. CONCLUSIONS: Recent outbreaks of zoonotic diseases associated with contact with animals in exhibition venues highlight concerns for disease transmission to public visitors. Only a handful of states have written guidelines for preventing zoonotic disease transmission in animal exhibition venues, and published recommendations currently available focus on preventing enteric diseases and largely do not address other zoonotic diseases or prevention of bite wounds.

Animal Diseases↗

PubMed1993

An estrogen receptor mutant exhibiting hormone-independent transactivation and enhanced affinity for the estrogen response element.

To study transactivation by the Xenopus laevis estrogen receptor (XER), we inserted one or two copies of a synthetic amphipathic helix at amino acid 276 of the XER. The XER mutants containing one or two copies of the amphipathic helix (XER/1AH and XER/2AH, respectively) and wild-type XER were expressed at similar levels. In transient transfection assays, XER/1AH exhibited only a modest, promoter-specific increase in transactivation. Constitutive (estrogen-independent) transcription of a synthetic promoter containing two estrogen response elements (EREs) was approximately 10-fold higher for the XER/2AH mutant than for wild-type XER. The XER/2AH mutant and wild-type XER exhibited similar 17 beta-estradiol dose-response curves for transactivation. In studies carried out over a broad range of DNA concentrations using the simple 2ERE-TATA promoter or a complex vitellogenin-derived promoter, the XER/2AH mutant exhibited an estrogen-dependent 2-3-fold increase in transactivation. A 2-3-fold increase in transactivation by XER/2AH was also observed using synthetic promoters in which the two EREs exhibit synergistic interactions with the NF1, AP1, or vitellogenin activator upstream activator sequences. Using a promoter interference assay to investigate intracellular interactions between the estrogen receptor and the ERE, we showed that binding of wild-type XER to the ERE was strongly estrogen-dependent. In the presence of 17 beta-estradiol, XER/2AH and wild-type XER exhibited similar promoter interference curves. In the absence of 17 beta-estradiol, the expression plasmid encoding the XER/2AH mutant achieved levels of promoter interference with 0.25-0.5 microgram of transfected DNA that were similar to those observed with 5-10 micrograms of the expression plasmid encoding wild-type XER. The ability of the XER/2AH mutant to activate transcription in the absence of estrogen therefore is likely to be related to the approximately 20-fold increase in its apparent ability to bind to the ERE. Since XER/2AH was unable to activate transcription from a glucocorticoid response element, enhanced binding of XER/2AH to the ERE did not result from a general increase in binding to DNA. The XER/2AH mutant appears to be the first nuclear receptor mutant to retain hormone-dependent transactivation and to exhibit enhanced hormone-independent binding to its hormone response element.

Animals↗

PubMed2006

The body as interactive display: examining bodies in a public exhibition.

'Body Worlds' is an exhibition of human bodies that is currently touring Europe, the Far East and the USA. The public display of 'real' human bodies has caused public controversy and debate about the moral and educational value of the exhibition. Relatively little academic research, however, has been undertaken to explore how visitors see and reflect on the exhibits. In this journal, Tony Walter recently examined messages people left in the exhibition's comment-books to reveal how people saw the bodies. His investigation provides interesting insights into people's understanding of and attitude to Body Worlds. This paper complements Walter's findings by analysing video-recordings of visitors looking at the 'plastinated' bodies at the showing of Body Worlds in London in 2002/03. The analysis reveals how people anatomise the exhibits and consider them in the light of their knowledge and experience of 'real' human bodies, such as those of other people and their own. The paper concludes with a discussion of how the observations and findings from the analysis bear upon debates on Body Worlds and in the sociology of health and illness.

Anatomy↗

PubMed1994

Computerized scientific exhibit in radiology: a valuable format for delivering scientific information.

The computerized scientific exhibit (CSE) is gaining acceptance as a tool for delivering scientific information at meetings of radiologic societies. CSEs allow presentation of more material in a more space-efficient manner than do conventional exhibits, and the viewer can control the order and detail in which material is reviewed. As a disadvantage, currently, the radiologist must use a support team and learn new tools to create a CSE. The preparation and cost may also be greater. Meeting attendees must overcome a reluctance to use computers to benefit from a CSE. Creation of a CSE has design, production, and presentation phases. A team of content authors, software author, graphics acquisition person, and project manager works together through brainstorming, conceptual ordering, storyboarding, prototyping, and selection of authoring tools to design the exhibit. Production must include use of common word processing and image file formats, as well as standardization of image resolution. Accurate equipment specification is needed to ensure that the exhibit can be run on the equipment provided by the meeting organizers. In addition, some security steps are needed to prevent misuse of the exhibit. In addition to display at assemblies, the CSE can be made available to a larger audience by delivery on media such as compact disks and the Internet and can be continually modified as new material becomes available.

Computers↗

PubMed1991

Myosin IB null mutants of Dictyostelium exhibit abnormalities in motility.

Cellular and intracellular motility are compared between normal Dictyostelium amoebae and amoebae lacking myosin IB (DMIB-). DMIB- cells generate elongated cell shapes, form particulate-free pseudopodia filled with F-actin, and exhibit an anterior bias in pseudopod extension in a fashion similar to normal amoebae. DMIB- cells also exhibit a normal response to the addition of the chemoattractant cAMP, including a depression in cellular and intracellular particle velocity, depolymerization of F-actin in pseudopodia, and a concomitant increase in cortical F-actin. DMIB- cells do, however, form lateral pseudopodia roughly three times as frequently as normal cells, turn more often, and exhibit depressed average instantaneous cell velocity. DMIB- cells also exhibit a decrease in the average instantaneous velocity of intracellular particle movement and an increase in the degree of randomness in particle direction. These findings indicate that if there is functional substitution for myosin IB by other myosin I isoforms, it is at best only partial, with myosin IB being necessary for maintenance of the normal rate and persistence of cellular translocation, suppression of lateral pseudopod formation and subsequent turning, rapid intracellular particle motility, and the normal anterograde bias of intracellular particle movement. Furthermore, it is likely that the behavioral abnormalities observed here for DMIB- cells underlie the delay in the onset of chemotactic aggregation, the increase in the time required to complete streaming, and the abnormalities in morphogenesis exhibited by DMIB- cells.

Actins↗

PubMed1988

Genetic differences in the frequency of acetazolamide-induced ectrodactyly in the mouse exhibit directional dominance of relative embryonic resistance.

Eleven of the common inbred strains of the mouse were surveyed for their teratogenic response to acetazolamide that was administered three times per os at 1,000 mg/kg (9 A.M. and 4 P.M. on day 9 and 9 A.M. on day 10). The products of conception were examined for gross malformations on day 15. One strain, SJL/J, exhibited maternal toxicity to the dosage regime and was excluded from the survey. Five strains exhibited significantly increased resorption rates after treatment. All strains responded with the expected malformation of postaxial forelimb ectrodactyly with a right-sided predominance. Nine of the strains could be assigned to one of four mutually exclusive classes of frequency of ectrodactyly and the tenth strain (BALB/cByJ) showed overlap between the two intermediate classes. The data suggest major genes determine the difference in sensitivity to ectrodactyly rather than a polygenic mode of inheritance. Induced cleft lip was found in four strains and one of these strains, SWR/J, exhibited a significantly higher frequency. The strain differences in sensitivity to induced resorption, forelimb ectrodactyly, and cleft lip were genetically independent. A reciprocal cross study was conducted with five of the strains from the four classes of frequency of ectrodactyly response in order to determine gene action. A significant maternal effect on the ectrodactyly response was found only with one of the strain pairs in the ten sets of reciprocal crosses with the five strains. When there was a significant difference between two strains, the F1 embryos exhibited dominance of relative resistance to ectrodactyly. The directional dominance of relative resistance to acetazolamide-induced ectrodactyly suggests that regulatory genes control the embryonic differences in frequency of ectrodactyly response to acetazolamide. By analogy with other metric traits of development that exhibit directional dominance, the genetic variation in ectrodactyly response that has been observed so far in the mouse embryo may not be involved with the primary target of acetazolamide teratogenesis.

Abnormalities, Drug-Induced↗

PubMed1993

Etoposide-resistant human colon and lung adenocarcinoma cell lines exhibit sensitivity to homoharringtonine.

Human colon (HCT116/VP48) and lung (A549B/VP29) adenocarcinoma cell lines selected for resistance to etoposide exhibited modified patterns of multi-drug resistance (MDR) that included a differential sensitivity to other DNA topoisomerase II inhibitors and to the plant alkaloids homoharringtonine, vinblastine, and vincristine. The resistance and cross-resistance drug phenotype of the A549B/VP29 cell line was different from that of the HCT116/VP48 cell line. The HCT116/VP48 cell line was 50-fold resistant to etoposide and 30-fold resistant to teniposide. The degree of resistance to other DNA topoisomerase II inhibitors was of a lower magnitude: Adriamycin, 9-fold; daunomycin, 3-fold; 4'-[(9-acridinyl)-amino]-methanesulfone-m-anisidide (m-AMSA), 3-fold; and actinomycin D, 6-fold. The HCT 116/VP48 cell line exhibited a 7-fold resistance to vincristine and a 2-fold resistance to vinblastine but was sensitive to homo-harringtonine. The A549B/VP29 cell line was 5-fold resistant to etoposide and 2-fold resistant to teniposide. The A549B/VP29 cell line exhibited a 2-fold resistance to Adriamycin but was sensitive to daunomycin and showed a 3-fold resistance to m-AMSA. This cell line was sensitive to actinomycin D. The A549B/VP29 cell line was 2-fold resistant to vinblastine and sensitive to homoharringtonine. Both cell lines (HCT116/VP48 and A549/VP29) exhibited no amplification of the human mdr1 DNA sequence, the 4.3-kb P-glycoprotein transcript, or the membrane P-glycoprotein. The sensitivity of cells exhibiting an MDR phenotype not mediated by P-glycoprotein suggests a potential use for homoharringtonine in treating tumors with this type of drug resistance.

Adenocarcinoma↗

PubMed1987

Mutations at the mei-41, mus(1)101, mus(1)103, mus(2)205 and mus(3)310 loci of Drosophila exhibit differential UDS responses with different DNA-damaging agents.

5 mutagen-sensitive mutants of Drosophila melanogaster, reported to perform normal or only slightly reduced excision repair of UV damage, were examined by an unscheduled DNA synthesis (UDS) assay. This assay measures the ability of cultured primary cells, derived from each mutant, to perform the resynthesis step in the excision repair pathway, following damage to cellular DNA by direct-acting alkylating agents, UV or X-irradiation. 2 mutants, classified as completely or partially proficient for both excision and postreplication repair of UV damage, mus(1)103 and mus(2)205, were found to give positive UDS responses only for UV damage. These mutants exhibit no measurable UDS activity following DNA damage by several different alkylating agents and X-rays. 3 mutants, classified as having no defect in excision repair, but measurable defects in postreplication repair of UV damage, mei-41, mus(1)101, and mus(3)310 exhibit 3 different response patterns when tested with the battery of agents in the UDS assay. The mutant mei-41 exhibits a highly positive UDS response following damage by all agents, consistent with its prior classification as excision-repair-proficient, but postreplication-repair-deficient for UV damage. The mutant mus(1)101, however, exhibits a strong positive UDS response following only UV damage and appears to be blocked in the excision repair of damage produced by both alkylating agents and X-irradiation. Finally, mus(3)310 exhibits no UDS response to alkylation, X-ray or UV damage. This is not consistent with its previous classification. Results obtained with the quantitative in vitro UDS assay are entirely consistent with the results from two separate in vivo measures of excision repair deficiency following DNA damage, larval hypersensitivity to killing and hypermutability in the sex-linked recessive lethal test.

Animals↗

PubMed2005

Seizure-prone EL/Suz mice exhibit physical and motor delays and heightened locomotor activity in response to novelty during development.

Seizure-prone EL/Suz mice have been studied as a model of multifactorial epilepsy for five decades. In prior behavioral studies, EL/Suz mice were shown to exhibit heightened locomotor activity, which implies a state of underlying hyperexcitability. The aim of the present study was to establish the premorbid behavioral development of basic motor skills and activity levels of EL/Suz mice, as compared with DDY mice, the control strain that is not seizure-prone. EL/Suz and DDY pups were monitored from Postnatal Day (PND) 3 to assess body weight, surface righting, negative geotaxis, forelimb grip strength, eye opening, habituation to a novel environment, and exploratory behavior in a two-compartment task. EL/Suz mice weighed less from PNDs 3 to 21 and exhibited delayed surface righting (PNDs 3, 5, 7) and negative geotaxis (PNDs 5, 7, 9) responses. EL/Suz and DDY mice differed in their habituation to a novel environment, with EL/Suz mice exhibiting higher activity, both within a single 10-minute session and across the 3 days of testing. EL/Suz and DDY mice also differed in the two-compartment task, with EL/Suz mice exhibiting increased locomotor activity and spending a greater amount of time in the light compartment. Thus, the present findings reveal that EL/Suz mice exhibit some developmental delays, altered habituation to a novel environment, and increased exploratory activity. Overall, the present results demonstrate that the behavioral and physiological phenotype of seizure-prone EL/Suz mice is deviant more than 2 months before the onset of seizure susceptibility.

Age Factors↗