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Biomedical subjects

S Gill

Publications and source records attributed to S Gill.

At least 73 records · Page 4Linked to original sources

Induction of osteopontin mRNA expression during activation of murine NK cells.

Osteopontin (OPN) is an extracellular phosphorylated glycoprotein expressed in bone, kidney, nervous tissue, bone marrow, and granulated metrial gland (GMG) cells in murine decidua. We recently demonstrated that GMG cells are differentiated natural killer (NK) lineage cells that share phenotypic, functional, and morphologic characteristics with adherent interleukin-2 (IL-2)-activated NK cells. We now show that conditions that induce resting splenic NK cells to develop into adherent, activated cells induce the expression of opn mRNA. Nonstimulated NK cells did not express opn mRNA detectable by Northern analysis. However, expression was evident by day 1-2 of culture of NK cells with IL-2, increased to high levels by day 4, and was maintained at high levels thereafter. Thus, expression of mRNA for OPN, a secreted protein associated with cell adhesion, embryonic development, tissue remodeling, and immune regulation, is up-regulated during the activation of NK cells.

Animals↗

Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas.

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.

Adult↗

Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma.

Human synovial sarcomas contain a recurrent and specific chromosomal translocation t(X;18)(p11.2;q11.2). By screening a synovial sarcoma cDNA library with a yeast artificial chromosome spanning the X chromosome breakpoint, we have identified a hybrid transcript that contains 5' sequences (designated SYT) mapping to chromosome 18 and 3' sequences (designated SSX) mapping to chromosome X. An SYT probe detected genomic rearrangements in 10/13 synovial sarcomas. Sequencing of cDNA clones shows that the normal SYT gene encodes a protein rich in glutamine, proline and glycine, and indicates that in synovial sarcoma rearrangement of the SYT gene results in the formation of an SYT-SSX fusion protein. Both SYT and SSX failed to exhibit significant homology to known gene sequences.

Amino Acid Sequence↗

Identification of variability of ribosomal DNA spacer from Pseudomonas soil isolates.

The polymerase chain reaction was used to amplify the spacer region located between the 16S and 23S ribosomal RNA genes of strains of Pseudomonas fluorescens and Pseudomonas putida isolated from peat bog, canola field, or arctic plants. Some of spacer region of four of the P. fluorescens strains examined, strains 64-3, 63-28, QP5, and R17-FP2, was about 515 base pairs (bp) in length, and contained the genes for tRNA(Ile) and tRNA(Ala). The DNA sequences of two strains from canola, 64-3 and 63-28, differed at only two positions. The sequences of the peat bog strains QP5 and R17-FP2 were identical. However, differences were noted between the DNA sequence common to the pair of strains 64-3 and 63-28 and the corresponding common sequence for strains QP5 and R17-FP2. These differences were mainly concentrated in two DNA segments of 10 and 19 bp, respectively. A probe for the 19-bp variable segment that occurs in the ribosomal spacer of strains QP5 and R17-FP2 recognized total DNA from these two strains, but not DNA from other bacteria of different origins. These results suggest the existence of a limited degree of variability within the 16S-23S ribosomal DNA spacer region, and that this variability may be useful to the recognition of particular Pseudomonas strains from environmental samples.

Base Sequence↗

Thrombolysis in acute myocardial infarction. The implementation of thrombolytic therapy in a coronary care unit in 1992.

In order to describe the execution of thrombolytic therapy in acute myocardial infarction (AMI) in a coronary care unit, case records of 427 admissions in 1992 due to definite or possible AMI were reviewed: 32% received thrombolytic therapy while 68% did not because of contraindications, delayed admission, advanced age or nondiagnostic ECG changes. Among cases otherwise eligible for thrombolytic therapy according to the instructions of the department, 32% did not receive thrombolytic treatment solely because of nondiagnostic ECG changes. There is an obvious need for implementation of improved early diagnostic tools in the decision-making of thrombolysis as for instance newer, sensitive biochemical markers and continuous vectocardiography.

Adult↗

Patterns of practice analysis for acute myocardial infarction.

OBJECTIVE: To assess the level of use of acetylsalicylic acid (ASA), beta-blockers and thrombolytic therapy--proven efficacious therapies in the management of acute myocardial infarction (AMI)--in contemporary patients admitted with AMI, and to assess the role of contraindications and other patient-specific factors in the use or nonuse of these treatments. DESIGN: The demographics and treatment course of patients admitted with a diagnosis of AMI were reviewed. Specifically targeted therapies were ASA, beta-blockers and thrombolytic therapy. Rates of use were calculated as 'gross utilization' (overall use) and 'adjusted utilization' (accounting for late presentation to hospital, initially equivocal diagnosis or contraindications). SETTING: Tertiary care hospital in suburban Vancouver, British Columbia. PATIENTS: A total of 372 consecutive patients admitted to Royal Columbian Hospital between September 1, 1990 and September 1, 1991. INTERVENTIONS: None. MAIN RESULTS: Gross utilization of ASA, beta-blockers and thrombolytic therapy was 71, 31 and 21%, respectively. The adjusted utilization rates for early (6 h or less) treatment with ASA was 66%; with early beta-blockers, it was 18% and was 100% for thrombolytic therapy. Adjusted late (more than 6 h, to hospital discharge) use of ASA and beta-blockers was 84 and 57%, respectively. CONCLUSIONS: With the exception of thrombolytic therapy, proven efficacious medical therapies for AMI appear underused at the study hospital. Ongoing educational efforts and continuing patterns of practice analyses are needed.

Adrenergic beta-Antagonists↗

The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome.

A high proportion of synovial sarcomas contain the reciprocal translocation t(X;18)(p11.2;q11.2). We have previously localized the breakpoint on the X chromosome between the X chromosome marker DXS255 and an ornithine aminotransferase (OAT) pseudogene region designated OATL2. Subsequently by fluorescence in situ hybridization (FISH) we provided evidence that YACs corresponding to the OATL2 locus spanned the break-point. In order to confirm the position of this breakpoint cosmids corresponding to the OATL2 region were isolated. Most of these cosmids mapped to four cosmid contigs designated C1-C4. Analysis of two contigs, C1- and C4, using FISH established that in four of six synovial sarcomas examined the breakpoint occurs between these two contigs: C1 lies distal to the break-point while C4 is proximal. In contrast we provide evidence that the breakpoint in the remaining two tumours mapped to a second pseudogene region called OATL1 that is telomeric to the OATL2 locus. This heterogeneity of the breakpoint position on the X chromosome explains why in previous mapping studies there have been discrepancies between the results obtained by different laboratories.

Chromosome Mapping↗

Is the cervical spine clear? Undetected cervical fractures diagnosed only at autopsy.

Undetected cervical-spine injuries are a nemesis to both trauma surgeons and emergency physicians. Radiographic protocols have been developed to avoid missing cervical-spine fractures but are not fail-safe. Three case reports of occult cervical fractures documented at autopsy in the face of normal cervical-spine radiographs and computerized tomography scans are presented.

Adolescent↗

The effects of twice and four times daily zidovudine on p24 antigenaemia in CDC stage II/III patients.

Reduction of HIV p24 antigenaemia by zidovudine was investigated in 34 HIV antibody-positive, asymptomatic patients in a randomised, double-blind, placebo-controlled trial. Zidovudine was shown to lower p24 antigen levels as effectively when administered twice daily as when administered four times daily. Serum levels of p24 antigen varied little over 18 weeks in patients taking placebo.

Adult↗

Detection of transforming genes by transfection of DNA from primary soft-tissue tumours.

A series of adult soft-tissue tumours were screened for the presence of activated oncogenes by transfecting tumour DNA into NIH3T3 mouse fibroblasts. In these studies an activated K-ras gene that contained a mutation at the second position of codon 12 (GGT----GAT) was found in a leiomyosarcoma. In addition, following transfection of DNA from a liposarcoma, we identified an activated gene that failed to hybridize to probes prepared from 10 known human oncogenes (K-ras, H-ras, N-ras, ret, met, trk, mas, dbl, raf and hst) that have previously been detected in DNA transfection experiments. BamHI-BamHI fragments of this activated gene of 3.5 and 8.5 kb were cloned from NIH3T3 secondary transfectants using a probe that detects the human alu family of highly repetitive DNA sequences. Repeat-free subclones of these BamHI fragments were used to map this gene to human chromosome 19 (p13.2-q13.3). Our studies also demonstrate that a subclone from one of the BamHI fragments detects a 3.0 kb transcript in primary and secondary transfectants.

3T3 Cells↗

Removing barriers to partnerships.

One of the six corollaries to high quality healthcare identified in a 1987 study indicated that a team approach is required, although it challenges the notion of the professional autonomy of the medical staff. There are both individual and delivery system barriers to formation of partnerships and resistance to the change process. Combined with different views between physicians and executives, partnership building is a complicated process, and a number of recommendations are suggested to promote better relationships.

Attitude of Health Personnel↗

Injuries of the spine sustained during rugby.

In 1984 JR Silver reported on 63 patients who had sustained serious injuries of their cervical spine as a result of games of rugby between the years 1952 and 1982. In this paper his results have been brought up to date. A further 19 players who were treated personally are reported, sustaining their injuries between 1983 and 1987. The mechanism of injury was still blows to the head or the head being driven into the ground. Seven injuries occurred in the scrums all were front row forwards. One was injured when the players charged, two players were inexperienced and the other cases all followed a collapse of the scrum after which the second rows continued to push. Five players were injured while tackling, six players were injured in a ruck and maul situation--in each case they were pushed to the ground while stooping to pick up the ball, other players piled on top of them (one player broke from the scrum and he endeavoured to retrieve a low ball and then fell striking his head). Further research was carried out by circularising all the spinal units in the United Kingdom to obtain the overall figures. It has been found that there has been a reduction in the number of injuries from ten in 1983 to five in 1986/7, presumably from a change in the laws. In order to determine whether a further change in the laws was necessary or whether the existing laws were adequate, research was carried out by video recording several games of rugby and analysing the games later in slow motion and determining how injuries occurred. Most of the injuries in these small number of games occurred in the ruck and maul situation. It was concluded that the majority of such injuries were not due to bad luck but were caused by irresponsible actions. The laws were still being broken and not being enforced. The existing laws were adequate since there has been a reduction in the number of injuries overall, particularly at first class and schoolboy levels, but were not enforced at junior levels-they were the main source of injury.

Athletic Injuries↗

Computer-directed stereotactic biopsy of intrinsic brain stem lesions.

Despite advances in the neuro-imaging of the brain stem, an accurate diagnosis of intrinsic lesions in this region requires tissue sampling and histological verification. We have performed a series of computer-directed stereotactic procedures in 12 patients with intrinsic brain stem lesions. A positive diagnosis was obtained in 11 cases and therapeutic intervention was possible in four. There was no operative mortality. Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, computer-directed stereotactic biopsy should be considered in all patients harbouring an intrinsic brain stem mass.

Adolescent↗

Lack of synergy between cisplatin and cytarabine against ovarian carcinoma in vitro.

Synergy has been reported for the combination of cisplatin and cytarabine in a murine model and in several human cell lines in vitro. Clinical trials are under way with this combination. However, we were unable to demonstrate any significant synergistic interaction between these two agents in two human ovarian carcinoma cell lines with either 4-hour or continuous concurrent exposure in vitro at drug concentration producing 1-2 logs of cell kill. Synergy between these two drugs may be limited to unique cell lines and tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Regions on plasmid pCU1 required for the killing of Klebsiella pneumoniae.

Plasmid pCU1 was Kik+ (promotes killing of Klebsiella pneumoniae). All Tn5 insertions within the tra region of pCU1 were Kik-. Two other regions, kikA and kikB, were needed. They may be separated on different plasmids, but both must be mobilized into Klebsiella pneumoniae. Establishment of one kik region in K. pneumoniae followed by receipt of the second did not lead to killing. Kik was therefore intracellular and required concerted and transient action of both regions.

DNA Transposable Elements↗