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Biomedical subjects

D A Wheeler

Publications and source records attributed to D A Wheeler.

50 records · Page 3Linked to original sources
PubMed1985

Molecular basis of altered mouse mammary tumor virus expression in the D-2 hyperplastic alveolar nodule line of BALB/c mice.

The preneoplastic D-2 hyperplastic outgrowth line, which was derived from a hormone-induced hyperplastic alveolar nodule (HAN) of a BALB/c mouse, was used for a detailed analysis of mouse mammary tumor virus (MMTV) expression. The D-2 HAN line has previously been shown to express viral RNA representative of the entire genome, although viral particles have been noted only rarely. The MMTV-specific mRNA, protein, and DNA content of the D-2 tissues was defined in an effort to better understand the molecular basis of the aberrant virus expression. Northern blotting techniques demonstrated the presence of properly processed 8.9 kb (genomic) and 3.6 kb (envelope) mRNA. Protein electroblotting procedures established the presence of properly processed viral core protein p28. In contrast, the envelope precursor polyprotein was not processed into detectable levels of gp52. Analysis of MMTV proviral content by Southern blot methodology revealed the presence of a newly acquired provirus which serves as a marker for the clonal nature of the D-2 line. The origin of the new provirus is unknown. Methylation studies established that the new proviral insert is hypomethylated and, therefore, is likely serving as the template for the MMTV expression observed in the D-2 HAN line. These characteristics of the D-2 line make it an excellent system in which to study the role, if any, of MMTV in the progression of D-2 preneoplastic tissues to the tumor phenotype.

Animals↗
PubMed1985

Coelomic fat ectopia in the liver.

We describe a pedunculated, mesothelial-covered liver mass contained in a mesothelial-lined sac. Microscopically, the mass was composed of mature adipose tissue that contained thick-walled arteries and large veins, fibrous tissue, and numerous bundles of smooth muscle. The lesion was thought to represent ectopic coelomic mesenchyme originally destined to form omentum or mesentery. The existence of this entity suggested that previously reported cases of hepatic adipose tissue masses (lipomas) might also have derived from ectopic coelomic mesenchyme. Along with the mesenchymal lesion in the liver, an unclassifiable mesenchymal tumor was present in the cerebellum. Whether the coexistence of the two mesenchymal tissue masses was fortuitous, or related, could not be determined from this solitary case.

Adipose Tissue↗
PubMed1984

P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster.

Mutations at the period (per) locus of Drosophila melanogaster disrupt several biological rhythms. Molecular cloning of DNA sequences encompassing the per+ locus has allowed germ-line transformation experiments to be carried out. Certain subsegments of the per region, transduced into the genome of arrhythmic pero flies, restore rhythmicity in circadian locomotor behavior and the male's courtship song.

Animals↗
PubMed1984

Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms.

We have isolated and analyzed DNA sequences encompassing the period (per) locus of Drosophila melanogaster. The location of this clock gene was delimited by the molecular mapping of chromosome aberrations at or very near the per locus. At least five RNAs are transcribed from this region. One of these transcripts, a 0.9 kb species, is strongly implicated in per's control of biological rhythms. Two independently isolated arrhythmic mutations at the per locus dramatically reduce the level of this transcript. Furthermore, the level of the 0.9 kb transcript is strongly modulated during a light/dark cycle. We discuss evidence, from previously reported genetic and phenotypic analysis of per's function, suggesting that this region may be complex and that several gene products from the per region, including this 0.9 kb transcript, may be involved in the different aspects of normal rhythmicity influenced by this clock gene.

Animals↗
PubMed1984

Ciliated hepatic foregut cyst.

This study describes a solitary unilocular cyst of the liver, lined by ciliated, pseudostratified, columnar epithelium supported by a loose, relatively acellular lamina propria. The cyst wall was composed of a prominent smooth muscle band, of up to three layers, surrounded by an outer fibrous capsule. These features distinguish the cyst from biliary cystadenoma and make it histologically similar to previously described ciliated bronchial and esophageal cysts. This ciliated hepatic cyst and similar bronchial and esophageal cysts appear to represent a common spectrum of derivatives from the embryonic foregut. Cysts of this type have not been generally recognized to occur in the liver.

Cysts↗
PubMed1984

Serologic and biochemical studies of a previously unclassified blood type B variant.

The designation B4 is proposed for a weak variant of type B blood found in a Salvadorian woman and her two daughters. The red cells were weakly agglutinated by anti-B and anti-A,B; the serum contained anti-B; and the saliva contained H but not B substance. Biochemical studies of the serum showed that the enzyme specified by the variant B gene had low activity and low affinity for both sugar donor and acceptor.

ABO Blood-Group System↗
PubMed1983

Transcription of mouse mammary tumor virus: identification of a candidate mRNA for the long terminal repeat gene product.

We have examined an assortment of preneoplastic and neoplastic mouse mammary tissues for the presence of an mRNA which could encode the putative long terminal repeat gene product of mouse mammary tumor virus. We report here the detection of a novel mouse mammary tumor virus-specific, polyadenylic acid-containing transcript in certain preneoplastic and neoplastic mammary tissue of BALB/c mice. The molecule is 1.6 kilobases in length and contains sequences from the transcriptional leader and the U3 region of the proviral DNA. The upstream terminus of the 3' information lies 75 to 80 nucleotides from the beginning of the long terminal repeat open reading frame, in close proximity to a consensus splice acceptor in the DNA. The transcript was detected in hormonally or chemically induced neoplastic, preneoplastic, and lactating mammary tissue of BALB/c mice, but not in preneoplastic or tumor tissue induced by exogenous viruses in any strain of mice examined. This implies that the RNA we observed is transcribed from an endogenous provirus template.

Animals↗
PubMed1979

Placenta-bound immunoglobulins.

Low pH eluates were prepared from trophoblasts derived from 8 term human placentas. A qualitative analysis for immunoglobulins revealed the presence of IgG, IgA, and IgM in these eluates. IgC-rich fractions were obtained by DEAE-cellulose chromatography of ammonium sulfate-concentrated eluates. These fractions were able to neutralize, in vitro, the catalytic activity of reverse transcriptases (RT) from several retroviruses. RT from baboon endogenous virus (BEV) seemed to be more susceptible to the neutralizing activity of some eluates. This was in contrast to RT from feline leukemia virus (FeLV) which were neutralized by eluates of leukocytes from chronic myelogenous leukemia. In contrast to previous and present results with purified IgG from leukemic leukocytes, the purified IgG from placenta eluates was incapable of RT neutralization. However, such purified IgG fractions inhibited mixed lymphocyte reactions.

Female↗
PubMedDate not supplied

The immunobiology of leishmaniasis.

Members of the genus Leishmania are important intracellular pathogens that produce either cutaneous, mucocutaneous, or visceral disease in many areas of the world. In humans as well as in other mammals, the parasite is inoculated through the skin as a flagellated, extracellular promastigote by its arthropod vector, the sandfly. Once in its mammalian host, the promastigote converts to its amastigote stage, which lacks an exteriorized flagellum and is found solely within mononuclear phagocytes during established infection. In vitro, human monocyte-derived macrophages and peritoneal macrophages from several species of rodents can ingest both promastigotes and amastigotes, and they can permit intracellular multiplication of amastigotes only. Although serum factors may play a role in the pathogenesis of the disease and in protection against reinfection, the resolution of leishmaniasis is dependent primarily on cell-mediated immune responses. There appears to be a complicated interplay between cell-mediated helper and suppressor activities. The outcome of infection in each type of leishmaniasis depends on the complex and intriguing interaction of virulence factors inherent in the parasite and genetically determined host defense mechanisms.

Animals↗
PubMedDate not supplied

Low-dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: a randomized controlled trial.

PURPOSE: Previous studies with intermittent interleukin-2 (IL-2) therapy using intermediate and high levels of IL-2 have demonstrated significant increases in the CD4 + T cell count in HIV-infected patients. Intermittent regimens are amenable to outpatient use, but severe adverse events are frequently experienced with intermediate- and high-dose levels of IL-2. Therefore in this study, the effect of daily, subcutaneous low-dose IL-2 therapy on safety and immunological endpoints was investigated to determine whether immunological benefit could be achieved without toxicity in HIV-infected patients also receiving highly active antiretroviral therapy (HAART). METHOD: A total of 115 patients were enrolled in the trial. Fifty-six asymptomatic HIV-infected patients who had CD4 + T cell counts less than 300 cells/microL at screening and a stable HIV viral load received low-dose IL-2 (1.2 million IU [MIU]/m 2 beginning dose) once daily in conjunction with HAART (IL-2 group). Fifty-nine patients received HAART alone (control group). RESULTS: A dramatic effect of IL-2 on the natural killer (NK) cell population was observed with mean increases of 156 cells/microL in the IL-2 group compared to 19.93 cells/microL in the control group (p <.001). Additionally, IL-2-treated patients experienced a statistically significant increase in the mean percentage of CD4 + T cells (3.52% increase) when compared to control patients (1.33% increase) (p <.001). The expanded CD4 + T cell population was primarily of the naive phenotype, with mean increases of 4.53% for the IL-2 group and 0.31% for the control group (p <.001 for between-group difference). In addition, a higher proportion of IL-2-treated patients (67%) compared to control patients (33%) achieved increases of greater than 50% in the CD4+ T cell count (p =.08). Adverse events of grade 3 or grade 4 toxicity were infrequent in the current study and were substantially lower by comparison to those in studies of intermittent dose IL-2 therapy. Also, negligible changes in the HIV viral load from baseline to final measurement were observed in both groups. A trend toward a reduced number of modifications of antiretroviral therapy was apparent in the IL-2 group when compared to control patients. CONCLUSION: Daily, low-dose subcutaneous IL-2 therapy in conjunction with HAART is safe and well tolerated and is effective in expanding lymphocyte cell types including NK cells and naive T cells in individuals who have <300 CD4+ T cells.

Adult↗
PubMedDate not supplied

Cytologic diagnosis of gastric composite adenocarcinoma-carcinoid.

The cytologic findings in brushings from a composite adenocarcinoma-carcinoid of the stomach are presented. Cytologic smears showed both adenocarcinoma and carcinoid cell populations while the endoscopic biopsy specimen showed only adenocarcinoma. This case illustrates the usefulness of obtaining both cytology and biopsy specimens at endoscopy for the evaluation of gastric lesions.

Adenocarcinoma↗
PubMedDate not supplied

Human immunodeficiency virus in the health care setting.

Dr. Wheeler reviews the mechanisms of HIV infection and discusses procedures and situations that place health professionals at risk. Prevention of HIV transmission, institutional management of occupational exposure, and postexposure prophylaxis are addressed.

Centers for Disease Control and Prevention, U.S.↗