PubMed Health⌕ Search

Biomedical subjects

P Fisher

Publications and source records attributed to P Fisher.

At least 19 recordsLinked to original sources
PubMed1992

Surface IgM mediated regulation of RAG gene expression in E mu-N-myc B cell lines.

Transgenic mice carrying either the c-myc or N-myc oncogene deregulated by the immunoglobulin heavy chain enhancer element (E mu) develop both pre-B and B cell lymphomas (E mu-c-myc and E mu-N-myc lymphomas). We report here that B cell lines derived from these tumors, as well as a line derived from v-myc retroviral transformation, simultaneously express surface immunoglobulin (a hallmark of mature B cells) as well as a common subset of genes normally restricted to the pre-B stage of development-including the recombinase activating genes RAG-1 and RAG-2. Continued RAG-1 and RAG-2 expression in these lines is associated with VDJ recombinase activity detected with a VDJ recombination substrate. Cross-linking of the surface immunoglobulin on these lines with an anti-mu antibody leads to rapid, specific and reversible down-regulation of RAG-1 and RAG-2 gene expression. We also find that a small but significant percentage of normal surface immunoglobulin bearing bone marrow B cells express the RAG-1 gene. These findings are discussed in the context of their possible implications for the control of specific gene expression during the pre-B to B cell transition.

Animals↗
PubMed1992

Isopentenoid synthesis in embryonic Drosophila cells: prenylated protein profile and prenyl group usage.

It has been established that vertebrates and yeasts modified a unique subset of polypeptides with farnesyl and geranylgeranyl residues. This observation has been extended to Drosophila Kc cells. [3H]Mevalonate was incorporated into 54 Kc cell peptides (18-92 kDa). As reported for mammalian cells, most of the labeled peptides had molecular weights between 21 and 27 kDa. C18 radio-HPLC tryptic digest profiles for delipidized, [3H]mevalonate-labeled (a) insect (Drosophila and Spodoptera frugiperda) and mammalian (Chinese hamster ovary met 18-2b) cells, (b) Kc cell nuclear lamin, and (c) a 23.5-kDa purified Kc cell GTP-binding protein were compared and analyzed. [35S]Cysteine-labeled Kc cells yielded a tryptic digest radio-HPLC profile which was congruent with that for [3H]mevalonate-labeled cells. A significant fraction (30-33%) of the doubly labeled tryptic peptides were eluted with greater than or equal to 93% acetonitrile. Kc cell nuclear lamin tryptic digests yielded a single 3H-labeled product which migrated as S-farnesylcysteine. The Kc cell 23.5-kDa GTP-binding protein's 3H-labeled oligopeptide(s)/amino acid(s) was geranylgeranylated and its tryptic digest profile was representative of prenylated proteins whose oligopeptides eluted with greater than or equal to 93% acetonitrile. Moreover, the 3H-labeled oligopeptide/amino acid profiles plus prenyl group patterns for [3H]mevalonate-labeled Kc and mammalian cell total extracts were similar. Collectively, these observations supported a prenylated protein spectrum and prenyl group usage as highly conserved eukaryotic cellular characteristics.

Animals↗
PubMed1992

Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene.

The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc null allele. Mice homozygous for the mutation died between 10.5 and 12.5 days of gestation. Histological analysis of mutant embryos revealed that organs and tissues expected at these stages of development were present. However, multiple defects were observed, primarily in tissues and organs that normally express N-myc. In particular, mutant hearts were underdeveloped, often retaining the S-shape more typical of 9-day-old embryos. In addition, cranial and spinal ganglia were reduced in size and/or cellularity. Most of the noted defects were more consistent with a role of N-myc in proliferation of precursor populations than with a block in differentiation per se, at least at these early stages. These results demonstrate that N-myc plays an essential role during development and clearly confirm that N-myc has a physiological function that is distinct from that of the other myc-family genes.

Alleles↗
PubMed1991

Comparison of shunt fraction estimation using transcolonic iodine-123-iodoamphetamine and technetium-99m-pertechnetate in a group of dogs with experimentally-induced chronic biliary cirrhosis.

Portosystemic shunt fraction estimation using transcolonic iodine-123-iodoamphetamine (IMP) has been previously validated relative to portal vein macroaggregated albumin injections using an experimental model of cirrhosis. Transcolonic technetium-99m-pertechnetate (TcO4-) has been proposed as an alternative tracer to IMP to study portal circulation in cirrhotic patients. We compared shunt fraction estimates from paired transcolonic IMP and TcO4- studies performed on a group of dogs before and after common bile duct ligation surgery. Pertechnetate over-estimated shunt fraction in 6/7 postoperative studies relative to IMP. A good correlation between the two methods was demonstrated, however, the slope of the regression line was substantially less than 1.0 with TcO4- values reaching 100% at IMP shunt values of approximately 60%. This apparent inability to accurately assess high shunt flows may limit the quantitative aspects of TcO4- studies on patients with severe portosystemic shunting.

Amphetamines↗
PubMed1990

IgH enhancer deregulated expression of L-myc: abnormal T lymphocyte development and T cell lymphomagenesis.

Transgenic constructs containing the murine L-myc gene under the control of the immunoglobulin transcriptional enhancer element (Emu) are expressed at unexpectedly high levels in thymocytes and proliferating T cells compared with cells from bone marrow and proliferating B cells. In contrast, double transgenic animals bearing constructs containing the L- and N-myc genes similarly linked to the Emu element maintain preferential L-myc expression in T cells but express the N-myc transgene preferentially in B cells. These results indicate that the L-myc gene contains elements that act in concert with the Emu element to allow preferential expression in T lineage cells. In correspondence to the expression pattern, Emu-L-myc transgenic mice show expanded thymic cortices and irregularly formed splenic follicles with expanded T cell areas. Moreover, the percentage of thymocytes positive for the surface marker 1C11, which defines thymic progenitor cells, activated T cells and preleukemic T cells, is dramatically raised in transgenic mice compared with normal littermates. Emu-L-myc transgenic animals are predisposed to clonal lymphoid tumors, most of which are T cell lymphomas. The relative incidence, latency period, and degree of malignancy of Emu-L-myc tumors compared with Emu-N- or c-myc tumors is consistent with a lower oncogenic potential of the L-myc gene. However, the Emu-L-myc tumors do not express detectable levels of endogenous myc family genes indicating that the L-myc protein can substitute for c- or N-myc in the generation and growth of lymphoid neoplasms.

Animals↗
PubMed1989

Digital image display station performance requirements based on physician experience with a prototype system.

The authors report on observations of and interviews with physicians using a prototype digital image display and reporting station. While the users generally agree that image quality is clinically satisfactory, they are unanimous in their opinion that improvements in the man-machine interface are required before case review by this mechanism is clinically acceptable in a production environment. A model image and information user interface is presented. It was developed in answer to the needs of radiologists and referring physicians operating in the imaging department of a community acute-care facility. In such an environment images and related information must be communicated quickly and often simultaneously to different parts of the department and hospital. The user interface with the management system and the management system itself must address the varied functions and the needs of both the medical and clerical staff. Image enhancement processes, for example, must be restricted to those that quickly provide significantly more perceivable diagnostic information. Little-used processes that may occupy significant portions of the display and the console's computing power must be trimmed or eliminated.

Computer Systems↗
PubMed1989

Portasystemic shunt fraction quantification using transrectal administration of iodine-123 iodoamphetamine in dogs with chronic bile duct ligation and after propranolol administration.

Following transrectal administration, 123I iodoamphetamine (IMP) has been shown in both animal and patient studies to be capable of detecting the presence of portasystemic shunting (PSS). However, the ability of this method to actually quantitate PSS in the presence of cirrhosis and propranolol has not been demonstrated. We studied nine dogs with hitologically proven cirrhosis induced by chronic bile duct ligation. After intravenous injection of propranolol, PSS were measured with both the IMP method and the standard of portal vein infusion of 99mTc macroaggregated albumin (MAA) given through a mesenteric vein catheter. Based on linear regression, a close relationship was seen, given by the equation: MAA = IMP 0.9 + 0.035, with correlation coefficient of 0.99. Thus, in dogs with cirrhosis secondary to chronic bile duct ligation and after propranolol administration, PSS can be quantitated with the transrectal IMP method.

Amphetamines↗
PubMed1988

Lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the whole lung in a group of 9 sheep. Submicronic aerosol droplets were delivered to unsedated sheep held in a sling-like frame. Best fits for clearance curves to single- and biexponentials were calculated. The monoexponential T50 for the aerosol clearance was 293 min +/- 74 SD. Background correction was found to have a minimal effect (approx. 10%). Biexponential fitting only marginally improved correlations in the 8 healthy sheep, but in one additional animal with clinical evidence of pneumonia, clearance was faster and biexponential fitting was substantially better. These clearance values in conscious sheep are longer than previous findings with 99mTc-DTPA in anesthetized sheep. There appears to be a wide variation of radioaerosol 99mTc-DTPA lung clearances among different species, sheep exhibiting a comparatively prolonged clearance profile.

Administration, Inhalation↗
PubMed1988

Studies of the 'adaptive' repair response in human lymphocytes and V79 cells after treatment with MNNG and MNU.

In bacteria, there is evidence that a damage inducible repair response system known as the adaptive response exists since pretreatment with low doses of a simple monofunctional alkylating agent leads to a decrease in both the lethal and mutagenic effects of a subsequent challenge dose of the agent. The evidence for an analogous system in mammalian cells has proved to be inconsistent to date. The induction of chromosome repair mechanisms in human cells by low-dose radiation from tritiated thymidine has been shown to make the cells refractory to the induction of chromosome aberrations by X-rays. The present communication investigates the induction of an adaptive response in human lymphocytes from four donors and V79 cells using SCE and mutation as endpoints and MNNG and MNU for the adapting and challenging treatment. It is clear that a reproducible model of the adaptive response in human lymphocytes is difficult to establish because of the variability between different donors and different culture times. In V79 cells, assays with much larger cell numbers are required to detect a reproducible response with such small changes in mutant frequency. To demonstrate an adaptive response conclusively in mammalian cells will probably require the use of more sensitive experimental protocols and alternative methods of administration of adaptive doses of mutagen.

Animals↗
PubMed1988

The OSOT Perceptual Evaluation: a research perspective.

Although the Ontario Society of Occupational Therapists (OSOT) Perceptual Evaluation has been widely used, it has never been standardized. A study was undertaken to examine the validity of the battery for differentiating neurologically normal persons from those who have been independently diagnosed as neurologically impaired. A group of 80 brain-damaged patients was compared with a matched group of 70 neurologically normal persons. Comparison of scores for the two groups supports the validity of the instrument for differentiating the neurologically normal from the perceptually impaired person. The distribution of scores suggests that the degree of impairment can be classified as mild, moderate, or severe. Finally, the OSOT Perceptual Evaluation is found to be a reliable procedure for the assessment of perceptual dysfunction.

Adult↗