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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

486 records · Page 27Linked to original sources

Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1.

A molecular clone containing part of the transforming gene from two human sarcoma cell lines, HT1080 and RD, has been obtained and shown to represent a new member of the human ras gene family. The transforming gene has undergone no major rearrangements and has not been amplified in either sarcoma cell line. The major transcript from the gene is 2,200 nucleotides long and is present at the same levels in both normal fibroblasts and tumour cells. The same gene is also activated in HL60, a promyelocytic leukaemia line and in SK-N-SH, a neuroblastoma line. The gene, N-ras, is located on chromosome 1.

Alleles↗

Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite.

HL-60, a cell line established from a patient with promyelocytic leukaemia, responds to a variety of inducing agents by ceasing division and acquiring some of the characteristics of either granulocytes or monocytes. Among the agents so far tested, only a comparative few occur naturally in vertebrates and would appear to have significant clinical potential in the treatment of leukaemic patients. One of the most promising of these is the dihydroxymetabolite of vitamin D3, 1,25(OH)2D3. This compound circulates in normal man and has a major role in calcium homeostasis. Moreover, it has recently been reported that 1,25(OH)2D3 increases the survival time of mice injected with myeloid leukaemia cells. We and McCarthy et al. have previously shown that HL-60 cells respond to near physiological levels of 1,25(OH)2D3 by rapidly acquiring a number of monocyte-like features. Here we document that these phenotypic changes are preceded by a marked decrement in the expression of the c-myc oncogene. In fact, the diminution in the level of c-myc mRNA parallels the dose dependency and metabolite specificity shown by the various other indicators of phenotypic change. In addition, we demonstrate that removal of vitamin D3, after the onset of maturational change, results in the reappearance of elevated myc mRNA levels. We believe this to be the first demonstration of a sequential relationship between the application of an exogenous inducing agent, a reduction in myc mRNA levels and the development of characteristics associated with normal cell maturation.

Animals↗

Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production.

Many receptors, in response to ligand activation, trigger inositol phospholipid breakdown, which leads to rapid intracellular responses. The sustained activation of this pathway is believed to be at least one of the factors involved in the stimulation of cell growth and there has been much speculation that certain oncogenes use this pathway to effect uncontrolled cellular proliferation. It has been suggested, by analogy with the receptor-mediated control of adenylate cyclase, that the receptor stimulation of inositol phospholipid metabolism is mediated through a guanine nucleotide regulatory protein (G-protein) called Gp (or Np). Although such a species has not been identified, there is now strong experimental evidence that this process is mediated by a G-protein distinct from the stimulatory and inhibitory G-proteins (Gs and Gi, respectively). The ras genes code for a plasma membrane protein, p21, whose only known biochemical property is a high-affinity GTPase activity. We show here that the expression of normal p21N-ras in NIH 3T3 fibroblasts leads to the coupling of certain growth factor receptors to stimulated inositol phosphate production. We propose that the N-ras proto-oncogene encodes a protein which couples the receptors for certain growth factors to the stimulation of phospholipase C. Thus, N-ras p21 may be the putative Gp or a functionally related protein.

Animals↗

Epidemiology of infections caused by gentamicin-resistant enterobacteriaceae and Pseudomonas aeruginosa over 15 years at the Nashville Veterans Administration Medical Center.

Nosocomial infections and gentamicin resistance were surveyed over 15 years at Nashville Veterans Administration Medical Center, and trends for Enterobacteriaceae and Pseudomonas aeruginosa were contrasted. Analysis of approximately 6,000 nosocomial infections indicated that four-fifths were caused by aerobic gram-negative bacilli. Three hospital-wide outbreaks caused by Enterobacteriaceae occurred; these three outbreaks were due to Serratia marcescens, Klebsiella pneumoniae, and Enterobacter cloacae, respectively. The outbreaks were temporally related to the emergence of gentamicin resistance. Detailed analysis of the recent outbreak due to Enterobacter indicated that an increasing prevalence of gentamicin-resistant E. cloacae predated nosocomial infections by several months; this pattern suggested that such outbreaks could be predicted. Molecular epidemiologic data pertaining to the preservation over a decade of genes encoding gentamicin resistance were reviewed. In contrast to Enterobacteriaceae, P. aeruginosa gradually and progressively developed resistance to gentamicin that spread in an endemic fashion, with parallel increases in nosocomial infections. This pattern appeared to relate to different modes of spread and persistence for resistant P. aeruginosa that may require unique methods for control.

Cross Infection↗

A quantitative in vivo comparison of six contrast agents by digital subtraction angiography.

Digital subtraction angiography (DSA) technology can now visualize many significant arterial structures from intravenous injections of contrast media. Image quality of these DSA studies is related to contrast agent enhancement. This study compares contrast agents of differing iodine concentration, viscosity, and osmolarity. A technique is described that utilizes a scanned projection digital radiographic system to compare quantitatively degrees of intra-arterial opacification after the administration of six intravenous contrast agents: iothalamate (at four different concentrations and in combinations with two different cations), diatrizoate, and ioxaglate. The quantitative arterial enhancement was compared in dogs utilizing an extra-period latin-square multiple change-over clinical trial design. The contrast agents span a range of organically bound iodine from 282 mg I/ml. When rate and volume of contrast agent injected are held constant, intra-arterial opacification is directly a function of the iodine concentration (mg I/ml) of the agent injected, while osmolarity and viscosity have no effect on opacification. These studies support the use of agents with high iodine concentration for maximum vascular visualization.

Angiography↗

Evaluation of enamel dental restoration interface by optical coherence tomography.

Evaluation of molar dental restorations on enamel is performed using optical coherence tomography (OCT) with 10 microm resolution. Images of approximately 50 microm failure gaps in the restorations are demonstrated and the OCT images are compared with x-ray and optical microscopy pictures. The results demonstrate the potential of the technique for clinical evaluation of dental restorations.

Algorithms↗

A method for selective tissue and bone visualization using dual energy scanned projection radiography.

Information contained in the x-ray energy spectrum can be used to produce selective radiographic images of bone or soft tissue. A method has been devised to separate bone and soft tissue based upon differences in photoelectric absorption and Compton scattering using an appropriate combination of images obtained with radiographic exposures at 70 KVP and 140 KVP. Since photoelectric absorption is highly dependent upon atomic number, high atomic number materials such as calcium can be easily separated from water density substances. Using a prototype system for line-scanned radiography, selective subtraction of bone or soft-tissue has been implemented. Because this method uses a conventional broad-spectrum x-ray source, it was necessary to develop a nonlinear polynomial approximation to estimate tissue and bone thickness. The model was verified with phantom studies using water and aluminum. The application of this dual-energy bone and soft-tissue separation to chest radiography is demonstrated. This method allows accurate estimation of tissue and bone thickness and should find application to chest radiography for improved lesion detection and for bone mineral assessment.

Animals↗

The efficacy of bilingual health advocacy in ethnic minority patients with cancer.

AIM: This research aims to establish the efficacy of introducing trained bilingual health advocates to non-English speaking cancer patients. METHOD: Male and female Bengali advocates received appropriate training. They were then given a group of patients to manage, while a control group received no such intervention. Outcomes were determined at the baseline and after three months. The study finally concludes in April 2000. RESULTS: The progress so far shows that the advocates had only recruited half of the expected number of Bengali cancer patients. Focus groups showed, however, that healthcare professionals felt that their training was inadequate to overcome the language and cultural barriers, and many were distressed that they were not meeting the needs of minority ethnic patients. CONCLUSION: The authors anticipate that this study will concur with research in other health sectors where bilingual health advocacy has been beneficial, and that future care will be better informed as a result.

Humans↗

The British version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the British language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. A total of 440 subjects were enrolled: 219 patients with JIA (17% systemic onset, 41% polyarticular onset, 33% extended oligoarticular subtype, and 9% persistent oligoarticular subtype) and 221 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the British version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Adolescent↗

Low-dose methotrexate in systemic onset juvenile chronic arthritis.

Twelve children with severe systemic juvenile chronic arthritis, all requiring high dose corticosteroids, have been admitted to a pilot study to evaluate the effect of low-dose methotrexate (mean dose: 8.5 mg/M2) on disease activity over a 6 month period. Definite improvement occurred in 4 children, allowing reduction of the steroid dose in 2 cases. Two children showed an acute flare of disease activity during the treatment period and in three, steroids had to be increased. Overall, side effects were rare with a rise in transaminases only occurring once. MTX blood levels taken on 14 occasions in 8 children documented absorption in all cases with a mean level of 3.45 x 10(-7) mol/l on a mean dose of 9 mg/M2. Low-dose MTX appears to be a safe drug in the short term treatment of severe systemic JCA with beneficial effect in about a third of patients. Long-term controlled trials will be needed to evaluate its role in the treatment of systemic disease as well as side effects.

Absorption↗

N-ras and human cancer.

Activated N-ras genes have been detected in a variety of human tumours and tumour derived cell lines. It has been proposed that mutation or amplification of an N-ras gene represents one of the key steps in the development of some human tumours. Here we discuss the various methods by which activated N-ras genes have been detected, the ways in which they have become activated, and their contributions to the transformed phenotype.

Animals↗

Amyloidosis in juvenile chronic arthritis: a morbidity and mortality study.

A retrospective study of 79 juvenile arthritic patients with reactive amyloidosis for a mean of 10 years (3 months-24.25 years) from the onset of amyloidosis was performed. Eighty percent of those treated with chlorambucil (n = 57) were alive compared with 23.5% of patients not treated with chlorambucil (n = 19) 10 years after diagnosis. Renal failure was the cause of death in 82.3% and infection in 11.7%. Side effects included one chlorambucil-treated patient who developed acute leukaemia, and seven patients who developed severe leucopenia and four thrombocytopenia. Fifteen patients are no longer on cytotoxic therapy and are in remission. Analysis of their fertility status showed that there were 5 normal births in 3 women and 2 terminations of pregnancy in 23 chlorambucil-treated women of child bearing age. Six women had ovarian failure. None of the male patients fathered a child.

Adolescent↗

Eliciting hyperacute xenograft response to treat human cancer: alpha(1,3) galactosyltransferase gene therapy.

Xenograft hyperacute rejection in humans occurs as a secondary response to a cellular glycosylation incompatibility with most non-human mammalian species. A key component of hyperacute rejection, alpha(1,3)galactosyl (agal) epitopes present on the surface of most non-human mammal cells, is bound by host anti-agal IgG antibodies leading to the activation of complement and, cellular lysis (1). The enzyme causing specific glycosylation patterns, alpha(1,3)galactosyltransferase [alpha(1,3)GT], directs the addition of agal to N-acetyl glucosamine residues in the trans Golgi apparatus in most mammalian species including Mus musculus, but not old world primates, apes or humans. In this report, we cloned both a truncated and full length murine alpha(1,3)GT gene into a retroviral vector backbone in order to transfer alpha(1,3)galactosyl epitopes into human A375 melanoma cells. Expression of agal epitopes on A375 cells after alpha(1,3)GT gene transfer was demonstrated using FITC-labeled ligand and FACS analysis. These cells were exposed to human serum for 30 minutes and > 90% of the agal expressing cells were killed by this treatment. These pretreated cells failed to establish tumors after implantation into athymic nude mice. This is the first report of retroviral vector transfer of the alpha(1,3)GT gene into human tumor cells in an attempt to elicit hyperacute rejection as a novel anti-cancer gene therapy strategy.

3T3 Cells↗