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W Morton

Publications and source records attributed to W Morton.

10 recordsLinked to original sources

Characterization of a molecular clone of HIV type 2 infectious for Macaca nemestrina.

A lambda phage clone containing a full-length HIV-2 provirus, designated HIV-2KR, was obtained from the genomic DNA of Molt4 clone 8 (Molt4/8) lymphoblastic cells infected with the HIV-2PEI2 strain. HIV-2KR is genetically distinct from known HIV-2 isolates, possessing both a unique deletion in the LTR promoter region, and a long rev reading frame. It is replication competent in vitro after transfection into Molt4/8 cells, replicates in a variety of established human T lymphoblastic (Molt-3, Molt4/8, SupT1, H9, C8166) and myelomonocytic (U937) cell lines, and displays prominent cytopathic effects on infection of Molt4/8 cells, reflecting usage of both CCR5 and CXCR4 coreceptors. In addition, HIV-2KR was found to be infectious for human and Macaca nemestrina peripheral blood lymphocytes, and primary human monocyte-macrophage cultures. Intravenous inoculation of cell-free virus into M. nemestrina resulted in infection characterized by transient, low-level viremia and modest temporary decline in CD4 lymphocyte numbers, making HIV-2KR the first HIV-2 molecular clone reported to be infectious for this primate species.

Amino Acid Sequence↗

Genetic variation in a human immunodeficiency virus type 2 live-virus Macaca nemestrina vaccine model.

Four pigtailed macaques were inoculated with an infectious, apathogenic human immunodeficiency virus type 2 (HIV-2) molecular clone (HIV-2KR) and subsequently challenged with a highly pathogenic strain, HIV-2287, together with two naive control animals. After challenge, two animals inoculated with a high dose of the immunizing strain were protected from CD4 decline and immunodeficiency. To examine the role of genetic heterogeneity in protection, fragments of the env gene were amplified from peripheral blood mononuclear cell DNA and plasma RNA of challenged animals by PCR, examined by using a heteroduplex tracking assay (HTA), and sequenced. By HTA, variation was detected principally within the V1 and V2 regions of envelope. Extent of variation in viral DNA clones as assessed by HTA correlated with inoculum size, as did the degree of variation in sequences of clones derived from viral DNA. Conversely, a rapid reduction in the number of plasma viral RNA variants was noted by HTA at 8 weeks postinfection in protected animals; this reduction was not present in naive or unprotected macaques. Sequences derived from plasma viral RNA were found to be more closely related than corresponding viral DNA sequences, and protection correlated with a significant reduction in variation in plasma RNA sequences in animals given the identical inocula of HIV-2287. Nonsynonymous mutations were significantly less prevalent in the protected animals. An additional potential glycosylation site was predicted to be present in the V2 region in all but one clone, and amino acid signatures related to protection were identified in viral DNA and RNA clones within both the V1 and V2 regions. Examination of the role of viral variation in this HIV-2 live-virus vaccine model may provide valuable insights into immunopathogenesis.

Amino Acid Sequence↗

Autoradiographic study of smooth muscle cell proliferation in spontaneously hypertensive rats.

1. The rate of smooth muscle cell proliferation in age-matched 1-4-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was compared using autoradiography. 2. Labelling index, defined as labelled cells/sum of labelled and unlabelled cells x 1000, was obtained from perfusion-fixed superior mesenteric and large mesenteric arteries. 3. In the large mesenteric arteries, the smooth muscle cell labelling indices were similar between the SHR and WKY at all age groups, except at 1 week of age when the smooth muscle labelling index was higher in the SHR. 4. In the superior mesenteric arteries, labelling indices were similar between the rat strains at all age groups. 5. We conclude that, in the SHR, a rapid proliferation of smooth muscle cells in the large mesenteric arteries occurred during the first week of life. This resulted in a higher number of smooth muscle cell layers in the media of muscular arteries. 6. The increased proliferation may play a role in the subsequent development of hypertension in the SHR.

Animals↗

Leukemia incidence by occupation in the Portland-Vancouver metropolitan area.

During a 15-year period in an urban area with over a million inhabitants, we identified 1,678 cases of leukemia among residents aged 16 or older. Case finding was done according to the methods of the National Cancer Institute (NCI) SEER program. Usual occupation was coded by a system based on the U.S. Census Bureau classification. According to age-standardized incidence rates for persons aged 16-67, significant excess leukemia risks were found for 14 male and 8 female occupation categories, with the larger number of male excess risk situations due to nonlymphatic leukemia. Lymphatic leukemia risks were significantly elevated among dentists, school teachers of both sexes, auto mechanics, gas station attendants, female assembly workers, and female laundry and dry cleaning workers. Nonlymphatic leukemia risks were significantly elevated among machinists, other metal tradesmen, heavy equipment operators, textile operatives, meat cutters, cannery workers, construction laborers, freight and stock handlers, policemen, and firemen. Risks of both types of leukemia were significantly elevated among registered and practical nurses and lumber mill workers. This study has not identified specific etiologic agents and exposures, but applied investigations aimed at disease control by prevention of cases are now possible in this community. Nationwide surveillance and control are recommended.

Adolescent↗

Skin cancer and water arsenic in Lane County, Oregon.

It was expected that the incidence of skin cancer would be related to the known high arsenic levels in water supplies of Lane County, Oregon. Incidence rates were based on all histopathologically confirmed cases among Lane County residents diagnosed during 1958-1971 and were compared to mean water arsenic levels measured during 1968-1974. Basal cell carcinoma had a mean annual incidence rate of 88 per 100,000, a 5:4::M:F sex ratio, and an increasing risk for both sexes in urban areas. Squamous cell carcinoma incidence was 50 per 100,000 and showed 2:1:M:F sex ratio but no urban predilection. Neither type of skin cancer was directly related to the arsenic levels as expected, although sporadic individuals with sufficient exposure could manifest the relationship. Fewer than expected drinking water sources were found to contain high arsenic content, so that the Lane County data do not necessarily contradict previous reports of positive correlation. The basal cell carcinoma pattern suggested that this disease might be potentiated by urban air pollutants.

Aged↗

Patient discharge planning documentation in an Australian multidisciplinary rehabilitation setting.

This article, drawing on data from 17 case studies, addresses problems in documentation of discharge planning in an Australian multidisciplinary rehabilitation center and the ways these were, or could be, overcome. The problems identified in the case studies were not specific to one discipline; they were due to inadequately defined guidelines and responsibility and poorly designed forms, and they possibly reflected the tendency for members of practice-oriented disciplines to see documentation as low on their list of priorities.

Forms and Records Control↗

T-cell responses to human AIDS virus in macaques immunized with recombinant vaccinia viruses.

There is much interest in developing vaccines against acquired immune deficiency syndrome (AIDS), which is caused by a retrovirus termed human immunodeficiency virus (HIV). Isolates of this virus include human T-lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV). Several approaches towards the development of an AIDS vaccine result in the production of antibodies in subprimates. These methods involve the use of: antigens isolated from the AIDS virus; viral antigens expressed by transfected cells or by recombinant vaccinia viruses; and particular synthetic peptides of viral antigens. Because T-cell-mediated immunity (in addition to antibodies) is involved in resistance to diseases and death caused by various enveloped viruses, we sought to determine whether potential AIDS vaccines can induce T-cell responses against the AIDS virus. Here we report that immunization of non-human primates, Macaca fascicularis (macaques), with recombinant vaccinia viruses that express LAV envelope glycoproteins gp41 and gp110 results not only in the production of antibodies against the LAV envelope antigens but also in the generation of T-cells that proliferate and produce the lymphokine interleukin-2 (IL-2), in response to stimulation with purified LAV. We believe this is the first report demonstrating T-cell-mediated immunity to the virus that causes AIDS.

Animals↗