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Biomedical subjects

K Robertson

Publications and source records attributed to K Robertson.

At least 55 records · Page 3Linked to original sources
PubMed1998

CSF, plasma viral load and HIV associated dementia.

Plasma viral burden has proven valuable in predicting the future course of systemic HIV related disease and the response to treatment. It is not known whether plasma or cerebrospinal fluid (CSF) viral burden can be used to predict onset of or response to treatment of nervous system disease. We propose a model of viral load mediated neurotoxicity underlying peripheral and central HIV associated neurological disease. The objective of this preliminary study was to assess the relationship of HIV associated neurological disease to quantitative viral load in plasma and CSF. 47 subjects (HIV- = 10, HIV+ = 37) participated in the study. Plasma and CSF samples were collected within a 3 h window. RT-PCR (Roche Amplicor Monitor) was utilized to assess HIV-1 RNA viral load in both plasma and cell free (centrifuged) CSF. Subjects underwent concurrent comprehensive neurological and neuropsychological evaluations. In general, systemic viral load, as measured in plasma, was greater than that found in cell free CSF. Cell free CSF HIV RNA viral load was significantly correlated with neurological dysfunction, whereas plasma viral load was not. The sole subject with an elevated CSF viral load (> 5 Log 10), had HIV associated dementia (HAD) on clinical examination.

AIDS Dementia Complex↗
PubMed1997

Hirschsprung's disease: genetic mutations in mice and men.

Hirschsprung's disease is a neuronal dysplasia of the hindgut, characterised by a loss of neurones, which affects about 1 in 5000 live births. Genetic factors have been implicated in the aetiology of this disease in about 20% of cases and a dominant pattern of inheritance has been revealed in several families. The pathogenesis of the aganglionosis is often attributed to a failure of migration of neural crest cells, although this has not been proven. Recently, mutations in a developmentally regulated receptor tyrosine kinase gene, ret, and mutations in the endothelin receptor-B gene (ENDR-B) have both been linked to familial Hirschsprung's disease in humans. Moreover, certain mutant mouse strains--namely piebald lethal and lethal spotted--exhibit striking similarities to the human condition. The mutation which gives rise to piebald lethal has now been found to be in the ENDR-B gene, and the mutation associated with lethal spotted occurs in the gene for endothelin-3 (ET-3), a ligand for ENDR-B. Two transgenic mouse lines have been developed which also reflect the human disease: ret-k-, which has a loss of function mutation of the ret gene, and ENDR-B null. In addition, the introduction of a Lac-Z reporter gene into neural crest cells of aganglionic mice has made it possible to study directly the fate of enteric neuroblasts which are affected by "Hirschsprung's-like" mutations. Here, we review the possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis. This review focuses on recent advances in our understanding of the genetic basis of the lesions which have been implicated in congenital forms of Hirschsprung's disease. Disruption of these genes in the mouse, either by transgenic "knockout" approaches or in mutant mouse lines, offers the prospect of greater understanding of both the cellular and developmental bases of the human disease.

Animals↗
PubMed1997

The hypothalamic-pituitary-adrenocortical axis in severe falciparum malaria: effects of cytokines.

Patients with malaria can have features of adrenal insufficiency. Because of the pathophysiological and clinical implications of an Addisonian state, the hypothalamic-pituitary-adrenocortical axis was assessed in nine Vietnamese adults with complicated malaria. A CRH test was performed on admission (in convalescence in five cases) and in six healthy controls. Basal plasma ACTH concentrations in the patients and controls were similar [median (range): 2.9 (0.2-9.7) vs. 3.5 (1.9-13.4) pmol/L, respectively; P > 0.1]. Serum cortisol levels were greater in the patients [882 (294-1682) vs. 190 (110-676) nmol/L; P < 0.01], but three (33%) had values within the control range. Basal serum corticosteroid-binding globulin concentrations were similar in patients and controls (P = 0.23). The post-CRH rise in plasma ACTH was attenuated in the patients [peak: 6.1 (0.9-23.2) vs. 14.5 (6.2-21.5) pmol/L in controls; P < 0.05]; basal and peak plasma ACTH correlated with plasma interleukin-6 in this group (rs > or = 0.60; P < or = 0.04). Serum cortisol responses to CRH were depressed in acute illness [peak 990 (394-1, 805) nmol/L or 10 (0-50%) above baseline vs. 500 (429-703) nmol/L or 160 (10-380%) in controls; P < 0.05]. The median estimated serum cortisol t1/2 was 4.6 h in the patients and 1.6 h in the controls. These data suggest that, relative to a normal stress response, primary and secondary adrenal insufficiency can occur in severe malaria but may be attenuated by increased circulating interleukin-6 concentrations and impaired cortisol metabolism. The benefits of stress-dose corticosteroid replacement are unknown but could be considered in hypoglycemic patients or those with a serum cortisol within or below the reference range.

Adrenocorticotropic Hormone↗
PubMed1997

Workplace violence. Prevalence, prevention, and first-line interventions.

Workplace violence is increasing, but through education, prevention, and man aging escalating crises, critical care nurses can help to minimize the negative consequences of violence. Critical care nurses are particularly prone to acts of aggression and acts of violence due to the stressful environment for them, their families, and their patients. Developing violence prevention skills and interpersonal communication skills, not always highly valued in a critical care environment, are important steps in deterring workplace violence. Although not all incidents of workplace violence can be prevented, recognizing the individual at risk for violence and intervening on the behalf of all involved is a responsibility of every employee including the critical care nurse.

Adult↗
PubMed1996

Absence of splenic latency in murine gammaherpesvirus 68-infected B cell-deficient mice.

Murine gammaherpesvirus 68 (MHV-68) is a natural pathogen of mice which causes an acute lung infection and establishes a latent infection in B lymphocytes. In this paper we describe the infection in transgenic B cell-deficient (muMT) mice, to determine whether a latent infection can be established in a mouse lacking circulating B lymphocytes. Little difference was observed in the acute lung infection, although there was a slight delay in virus clearance in the muMT mice. This indicates that antiviral antibody is of little importance in the resolution of the lung infection. Neither free nor latent virus could be detected in the spleen in the muMT mice. In addition, these mice did not develop MHV-68-induced splenomegaly. These data suggest that within the lymphoid compartment B lymphocytes are the sole reservoir for MHV-68 infection in vivo, confirming earlier work which identified B cells as the site of latent infection based on cell fractionation studies. In addition, our study shows that CD4-driven lymphocyte expansion leading to splenomegaly is dependent on the presence of MHV-68-infected B cells in the spleen. Although no free virus was detected (using conventional biological assays) in the lung after the resolution of the acute infection, MHV-68 genome was detected in the lungs of both control and muMT mice by PCR analysis. This suggests that cells in the lung may act as a reservoir of latent virus which is independent of the B lymphocyte infection.

Animals↗
PubMed1996

The correlation between neuropsychological and neuroanatomic changes over time in asymptomatic and symptomatic HIV-1-infected individuals.

To determine the relationship between neuroanatomic and neuropsychological changes in both asymptomatic and symptomatic HIV-1-infected individuals, we conducted a longitudinal study of 47 HIV-infected individuals, 15 of whom were asymptomatic and 32 of whom had either AIDS-related complex or AIDS. To measure neuroanatomic change over a 30-month period, we conducted quantitative MRI measures of bicaudate/brain ratio (BCR) and bifrontal/ brain ratio. A comparison of change over time between BCR and neuropsychological performance showed a correlation between increase in atrophy and worsening in certain cognitive functions. The correlation held for both asymptomatic and symptomatic groups, with more pronounced changes in the symptomatic group.

AIDS Dementia Complex↗
PubMed1996

Viral Load and Neuropsychological Functioning in HIV Seropositive Individuals:A Preliminary Descriptive Study.

We have theorized a direct relationship between viral burden and deleterious effects on the central nervous systems. It was hypothesized that HIV+ individuals would manifest poorer neuropsychological functioning after increased viral load. To address this, we compared viral burden to neuropsychological performance in subjects who participated in ACTG 116-118. Plasma samples and neuropsychological assessments completed at the same time were available for 64 observations on 21 subjects. Subjects who had a viral peak of over 1000 TCID per ml were classified as high viral load, those who did not as low viral load. Mean performances of the high viral load subjects were poorer, even though baseline performances were slightly poorer in the low viral load group. Mean post-viral peak performances were poorer than pre-viral peak performances. Declines in neuropsychological performance were found significantly more often in the high viral load group. These findings support the viral load hypothesis.

HIV Infections↗
PubMed1996

Forced over-expression of the myeloid zinc finger gene MZF-1 inhibits apoptosis and promotes oncogenesis in interleukin-3-dependent FDCP.1 cells.

The myeloid zinc finger protein MZF-1 is important in hematopoiesis. Previous studies have found that reducing expression of MZF-1 inhibited G-CSF-driven human marrow colony formation assays. In this study we found that retrovirally overexpressing MZF-1 in IL-3-dependent FDCP.1 cells inhibited their apoptosis when IL-3 was withdrawn. The MZF-1-transduced FDCP.1 cells also formed tumors when injected into congenic mice, whereas control FDCP.1 cells did not.

Animals↗
PubMed1995

Reduction of pain and nausea after laparoscopic sterilization with bupivacaine, metoclopramide, scopolamine, ketorolac, and gastric suctioning.

OBJECTIVE: To determine whether postoperative pain and nausea after laparoscopic sterilization can be reduced with a combination of bupivacaine, metoclopramide, scopolamine, ketorolac, and gastric suctioning. METHODS: Women undergoing outpatient laparoscopic sterilization were randomized to protocol management or nontreatment groups. Each patient received standard general endotracheal anesthesia. Protocol subjects received intramuscular ketorolac 60 mg and scopolamine 0.25 mg, intravenous metoclopramide 10 mg, and gastric suctioning; bupivacaine (2.5 mg/mL) with epinephrine (5 micrograms/mL) was injected at trocar sites and dripped onto the fallopian tubes. The nontreatment group served as controls. Visual analogue scales were used to evaluate pain and nausea (measured in millimeters). Demographic characteristics, postoperative requirements for analgesics and antiemetics, time to discharge, and unscheduled admission were also evaluated. RESULTS: During a 7-month period, 71 women were enrolled. Protocol subjects (N = 35) reported pain severity of 27.9 +/- 19.1 mm (mean +/- standard deviation), whereas controls (N = 36) reported 59.3 +/- 23.3 mm (P < .001). Fourteen protocol patients requested additional pain medication, compared with 29 controls (P < .001). Protocol patients indicated a nausea severity of 9.9 +/- 18.7 mm, whereas the controls reported 38.8 +/- 35.5 mm (P < .001). Only one protocol patient required nausea medication, compared with nine controls (P < .02). Severity of pain correlated with severity of nausea (r = 0.38166, P < .001). Protocol patients were discharged from the outpatient surgery unit in 148.6 +/- 45.0 minutes, compared with 176.4 +/- 58.5 minutes for controls (P < .03). CONCLUSION: This regimen reduced the severity of pain and nausea after outpatient laparoscopic sterilization. The need for additional analgesics and antiemetics was also reduced. Protocol patients were discharged earlier than controls. These benefits seem to accrue without significant risk. We believe that this regimen may also be useful in other ambulatory laparoscopic procedures.

Analgesics, Non-Narcotic↗
PubMed1995

Expression of ret in the chicken embryo suggests roles in regionalisation of the vagal neural tube and somites and in development of multiple neural crest and placodal lineages.

In a screen for receptor tyrosine kinase genes regionally expressed in the developing hindbrain, we cloned and characterised the chicken ret gene. Data derived from studies of congenital human disease and from disruption of murine ret have demonstrated roles for ret in development of the kidney and enteric nervous system; the latter has been most well-studied in the avian embryo. In agreement with studies of the mouse embryo, we find expression of ret in both the intermediate mesoderm and the enteric nervous system. However, we additionally detect transcripts specifically in the vagal neural tube prior to the migration of enteric crest precursors, suggesting a possible earlier function in regionalisation of the neural tube and vagal neural crest. This spatial restriction in the neural tube is modulated by retinoic acid, but is not coordinately regulated with RAR-beta which shares a common anterior limit of expression with ret in normal embryos. Widespread expression of ret in placodal and neural crest derivatives raises the possibility of other roles in the development of the peripheral nervous system. In addition, ret may function in the spatial organisation of the epithelial somite, where it might play a role in the specification of anterior dermamyotome.

Amino Acid Sequence↗
PubMed1994

Dysregulated bcl-2 expression inhibits apoptosis but not differentiation of retinoic acid-induced HL-60 granulocytes.

The bcl-2-proto-oncogene appears to contribute to the development of certain malignancies by inhibiting programmed cell death (apoptosis). Mature granulocytes show a markedly limited life span and rapidly undergo apoptosis. To further define the relationship between apoptosis and granulocyte differentiation, we used retroviral vector-mediated gene transduction to introduce the normal bcl-2 gene into the HL-60 myeloid leukemia cell line and determined the response of these bcl-2-transduced HL-60 cells to the induction of granulocyte differentiation by retinoic acid (RA). Although the bcl-2-transduced HL-60 cells showed the same differentiative response to RA as did the parental HL-60 cells, the life span of the RA-induced, bcl-2-transduced HL-60 granulocytes was markedly prolonged compared with that of the RA-induced parental HL-60 granulocytes. DNA fragmentation studies indicate that this prolonged life span resulted from diminished apoptosis in the bcl-2-transduced cells. These studies indicate that bcl-2 is involved in regulating apoptosis in maturing granulocytes. Because bcl-2 over-expression did not interfere with RA-induced granulocyte differentiation, it appears that granulocyte differentiation and apoptosis are under distinct and separate regulatory controls.

Apoptosis↗
PubMed1994

Resistance of HLA-G and HLA-A2 transfectants to lysis by decidual NK cells.

Trophoblast cells from normal first trimester pregnancies have been shown to express the nonclassical Class I molecule, HLA-G, which is nonpolymorphic and has a heavy chain of 40 kDa. These HLA-G-expressing trophoblast cells infiltrate into maternal decidua, which contains abundant uterine-specific CD56bright natural killer (NK) cells. We believe HLA-G may act as a protective molecule against decidual NK lysis and thus allow trophoblast survival in the maternal tissues. To test this hypothesis, we have constructed HLA-G and HLA-A2 transfectants using LCL 721.221 HLA-null cells. We observed that both of these antigens protected target cells from NK effectors isolated from decidua or peripheral blood, although the effect of HLA-G is not as marked as that of HLA-A2. Our results, therefore, show that in this experimental system expression of a nonclassical Class 1 HLA molecule is also correlated with NK resistance in the same way as a classical Class I HLA molecule.

Blotting, Northern↗
PubMed1993

Differential nuclear expression of enhancer A DNA-binding proteins in human first trimester trophoblast cells.

In order to investigate the possible molecular regulatory mechanisms that repress classical HLA class I and stimulate nonclassical HLA-G and E-class I gene transcription in human trophoblast cells, we searched for the nuclear expression of the enhancer A DNA-binding proteins of the KBF1/NF-KB/rel family. Using both purified extravillous cytotrophoblast and villous syncytiotrophoblast from first trimester human placenta, it appeared that members of this family were present in the cytotrophoblast and absent in the syncytiotrophoblast. First, using the double stranded enhancer A DNA nucleotidic sequence that contains the palindromic KB site, known to be the binding site of the p50 subunits of KBF1-NF-KB and c-rel factors, we demonstrated, by band-shift assay, that binding activity, inhibited by addition of anti-p50 polyclonal serum, was present in cytotrophoblast as well as control maternal decidual cells, embryonic fibroblasts, and the trophoblast-derived JAR cell line. In contrast, this DNA-protein complex was undetectable in syncytiotrophoblast nuclear extracts. The specificity of this protein-DNA complex was further demonstrated by its disappearance upon competition with an excess of cold homologous nucleotidic competitor. Other nucleoprotein complexes were also detected in all nuclear extracts, including syncytiotrophoblast, that were competed out by an excess of cold enhancer A competitor DNA but were not affected by the addition of anti-p50 or anti-NF-KB sera, suggesting the presence of additional enhancer A-binding factors different from the KBF1/NF-KB/rel family. Second, using a Western immunoblot analysis, a doublet around 85 kDa was specifically stained by the same anti-p50 serum in cytotrophoblast, maternal decidual cells, embryonic fibroblasts, and the JAR nuclear extracts whereas no signal was obtained in syncytiotrophoblast. Finally, immunofluorescence cell staining using the same anti-p50 serum showed a positive staining in both cytoplasm and nucleus of cytotrophoblast and its absence in syncytiotrophoblast. We hypothesize that this enhancer A DNA-binding factor might represent the c-rel trans-acting factor, related to p50/KBF1/NF-KB proteins, and we discuss its possible relevance to the HLA class I transcription in human tissues.

Base Sequence↗
PubMed1992

Tolerance of self induced in thymus organ culture.

F liver protein occurs in serum at low concentration, and therefore induces tolerance of self only in T cells. T cells which mature in cultured thymus lobes in the absence of this protein become reactive towards it but can be prevented from doing so by exposure to the protein while in culture. The threshold of tolerance induction for this soluble antigen is estimated in this way at approximately 1 microgram/ml, which is slightly less than the threshold of response of primed T cells in a proliferation assay. Freshly isolated thymocytes do not display reactivity to self-F protein, indicating that T cells normally become tolerant while still within the thymus.

Animals↗
PubMed1992

Identification and characterization of a novel high-molecular-weight form of the integrin alpha 3 subunit.

The integrin alpha 3 beta 1 is a multiligand extracellular matrix receptor found on many cell types. Immunoprecipitations of 125I-surface-labeled prostate carcinoma cell lines, DU145 and PC-3, with the anti-alpha 3 integrin monoclonal antibodies J143 or PIB5, resulted in the coimmunoprecipitation, along with the expected alpha 3 beta 1 heterodimer, of a polypeptide with a molecular mass of 225 kDa. This protein could also be copurified with the 155-kDa alpha 3 and 115-kDa beta 1 subunits upon affinity chromatography of 125I-surface-labeled cell extracts on anti-alpha 3 antibody-Sepharose columns. Upon reduction, this 225-kDa protein generated 130- and 95-kDa polypeptides, while the 155-kDa alpha 3 subunit generated 130- and 25-kDa polypeptides. The 225-kDa protein did not generate a 25-kDa polypeptide. Deglycosylation and reduction of the 225-kDa protein resulted in the generation of 110- and 95-kDa polypeptides, while deglycosylation and reduction of the 155-kDa alpha 3 resulted in a 110-kDa polypeptide identical in size to the 110-kDa polypeptide generated from the 225-kDa protein. Peptide maps generated from the 110-kDa components of the 225-kDa polypeptide and the 155-kDa alpha 3 integrin subunit were identical, as were their N-terminal amino acid sequences. An antibody directed against the cytoplasmic domain of the alpha 3 subunit immunoprecipitated the 225-kDa polypeptide in addition to the 155-kDa alpha 3 subunit. Furthermore, Northern blot analysis of RNA from DU145 and PC-3 cells with a human alpha 3 cDNA probe identified an mRNA species of 6.2 kb in addition to a major mRNA species of 4.3 kb. The larger mRNA species, which is of an appropriate size for encoding a polypeptide of approximately 220-kDa, was not detectable in cells which did not express the 225-kDa protein. These data demonstrate that the 225-kDa polypeptide represents a novel integrin alpha 3 subunit consisting of the alpha 3 integrin heavy chain disulfide-bonded to a 95-kDa polypeptide which may represent an alternative "light" chain to the 25-kDa light chain of the alpha 3 subunit.

Amino Acid Sequence↗