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R M Slater

Publications and source records attributed to R M Slater.

At least 55 records · Page 3Linked to original sources
PubMed1989

Use of survivors' cardiorespiratory values as therapeutic goals in septic shock.

The responses to therapy of 29 patients in septic shock are described. Patients received controlled plasma volume expansion followed by infusions of norepinephrine, dobutamine, and dopamine to achieve appropriate therapeutic goals. Increases in oxygen delivery (Do2) from 605 +/- 40 (SEM) to 843 +/- 27 ml/min-m2 (p less than .001) were associated with increases in oxygen consumption (Vo2) from 130 +/- 6.8 to 169 +/- 6.2 ml/min.m2 (p less than .001). The overall hospital survival rate was 52%. We suggest that the rational use of adrenergic agents and the achievement of appropriate physiologic end-points for therapy not only result in the reversal of hypotension, but also maintain or increase Do2 and Vo2, and may improve survival.

Adult↗
PubMed1989

The effect of acutely administered phenytoin on vecuronium-induced neuromuscular blockade.

Phenytoin was administered intravenously in a dose of 10 mg kg to a group of patients in whom steady state neuromuscular blockade had been established with an infusion of vecuronium. A control group of patients were given 0.9% saline instead of phenytoin. Administration of phenytoin produced significant augmentation of neuromuscular blockade (p less than 0.001). The possible mechanism of this effect is discussed.

Adult↗
PubMed1989

Autosomal dominant aniridia linked to the chromosome 11p13 markers catalase and D11S151 in a large Dutch family.

In a large pedigree with autosomal dominant aniridia, we found close linkage between the aniridia locus AN2 and the markers catalase (CAT) (zeta = 7.27 at theta = 0.00) and D11S151 (zeta = 3.86 at theta = 0.10) flanking the AN2 locus on 11p13. Positive lod scores were also obtained for the 11p13----11p14 markers D11S16 and FSHB with the linkage group CAT/AN2/D11S151. We conclude that the autosomal dominant aniridia in this family is due to a mutation at the AN2 locus on 11p13. We have excluded linkage (zeta less than -2 at theta less than 0.18) between the aniridia and the chromosome 2p25 marker D2S1 (linked to ACP1).

Aniridia↗
PubMed1988

Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours.

In this paper we describe the analysis of genetic changes in chromosome 11 in Wilms' tumours. Using a range of probes for regions 11p15, 11p13 and 11q we have screened DNA from 14 Wilms' tumours together with control DNA obtained from the patients' lymphocytes and their parents. We have been able to demonstrate loss of heterozygosity in 5 of the 14 different Wilms' tumours. In three of these five tumours, loss of heterozygosity did not involve markers for 11p13, 11p15.4 or the proximal region of 11p15.5, but only some markers assigned to the most distal part of 11p15.5. In two of these tumours we could demonstrate unequal mitotic recombination in 11p with breakpoints in the hypervariable regions 5' of the insulin gene and/or 3' of the HRASI proto-oncogene. In one tumour, from a Beckwith-Wiedemann patient, all markers for the region 11q13-pter became hemizygous; the region 11q13-qter remained heterozygous. These results demonstrate that loss of heterozygosity in Wilms' tumours may not necessarily involve the proposed Wilms' tumours locus at 11p13 but may be limited to 11p15.5. This suggests that not only the 11p13 region, but also the 11p15.5 region is involved in Wilms' tumour development. The possible role of both regions in the development of Wilms' tumour is discussed.

Alleles↗
PubMed1988

Morphological transformation by early region human polyomavirus BK DNA of human fibroblasts with deletions in the short arm of one chromosome 11.

Human fibroblasts derived from four individuals with various deletions in the short arm of one chromosome 11 were susceptible to morphological transformation by early region BK virus DNA, whereas diploid human fibroblasts were not. This difference in susceptibility to transformation by early region BK virus DNA might be explained by a putative 'transformation suppressor' locus situated within the deleted region on the short arm of chromosome 11.

BK Virus↗
PubMed1988

Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA.

Human embryonic fibroblasts with a large deletion (11p11.11p15.1) in the short arm of one chromosome 11 (del-11 cells) appeared to be susceptible to transformation by early human papillomavirus type 16 (HPV-16) DNA, whereas diploid human embryonic fibroblasts were not. This difference in susceptibility might be explained by the absence of a tumor suppressor gene located within the deleted part on the short arm of chromosome 11. The presence of abundant viral early-gene transcripts in transformed cells suggests that transformation was induced by an elevated level of an HPV-16 early-gene product(s). The low transcriptional activity of HPV-16 in diploid cells may indicate that cellular genes affect viral transcription. Interruption of the HPV-16 E2 early open reading frame is probably required for high-level HPV-16 early-gene expression driven from the homologous enhancer-promoter region.

Blotting, Southern↗
PubMed1987

Phenytoin infusion in severe pre-eclampsia.

Intravenous phenytoin sodium was given as a high-dose infusion (10 X 8-18 mg/kg) for anticonvulsive prophylaxis to 2 eclamptic patients and to 24 patients with moderate to severe pre-eclampsia. There were no major maternal or neonatal side-effects. Plasma phenytoin levels were within the therapeutic range (7-20 mg/l) at 30 min and 6 h after the infusion in all patients, and remained at a therapeutic level in 21 patients after 12 h. After a second dose of phenytoin in 19 patients, drug levels were within the therapeutic range at 24 h.

Female↗
PubMed1987

Regional localization of DNA probes on the short arm of chromosome 11 using aniridia-Wilms' tumor-associated deletions.

We are interested in the precise localization of various DNA probes on the short arm of chromosome 11 for our research on the aniridia-Wilms' tumor association (AWTA), assigned to region 11p13 (Knudson and Strong 1972; Riccardi et al. 1978). For this purpose we have screened lymphocyte DNA and material derived from somatic cell hybrids from individuals with constitutional 11p deletions with a range of available probes: D11S12; calcitonin/CGRP (CALC1/CALC2); insulin (INS); Harvey ras 1 (HRAS 1); beta-globin gene cluster (HBBC); human insulin-like growth factor 2 (IGF-2); parathyroid hormone (PTH); human pepsinogen A (PGA). Using this material, it has been possible to map all probes used, except insulin, outside the region 11p111-p15.1, resulting in an SRO (same regional overlap) of 11p15.1-p15.5 for most probes. We found an SRO for PGA of 11p111-q12 and an SRO for CALC2 of 11p15.1-p15.5 or 11p111-q12. We have localised the insulin gene to band 11p15.1.

Animals↗
PubMed1987

Effect of salbutamol and suxamethonium on the plasma potassium concentration.

In a double-blind randomized study, patients received premedication with lorazepam 0.04 mg kg-1 and salbutamol 0.1 mg kg-1 or lorazepam 0.04 mg kg-1 and placebo given orally 2.5-3 h before anaesthesia. The plasma potassium concentration was measured at the time of premedication, before the induction of anaesthesia and at selected intervals after suxamethonium 1 mg kg-1 i.v. The plasma potassium concentration was lower in those patients who received salbutamol than in those given placebo, and remained lower at all the subsequent sample times. Oral salbutamol did not appear to affect the incidence of suxamethonium related muscle pain.

Adolescent↗
PubMed1987

Characterization of the blast cells in acute leukemia with translocation (4;11): report of eight additional cases and of one case with a variant translocation.

Eight new cases (five adults and three children) of acute leukemia characterized by the presence in bone marrow cells of a t(4;11)(q21;q23)and one similar case, a child, with a t(1;11)(p32;q23) are reported. All patients were diagnosed as having acute lymphoblastic leukemia (ALL) with high-risk features. Immunologically the blast cells of the nine cases showed a strikingly consistent immature lymphoid phenotype, i.e., TdT+, HLA-DR+, B4(CD19)+, CALLA(CD10)-, Smlg-, cmu-, BA-2(CD9)+ corresponding to a "null ALL." In addition, six of nine cases expressed the myeloid marker VIM-D5(CD15). By double immunofluorescence staining it was determined that the VIM-D5(CD15) antigen was expressed by terminal deoxynucleotidyl transferase-positive blast cells, excluding the possibility of double leukemia. In five cases investigation of the Ig heavy chain genes by Southern blot analysis showed clonal rearrangement of both Ig heavy chain gene alleles. These data suggest that the blast cells involved in t(4;11) leukemia represent early B-cell progenitors with "aberrant" expression of myelomonocytic features, possibly related to the 11q23 breakpoint.

Adolescent↗
PubMed1986

Imbalanced MHC class II molecule expression at surface of murine B cell lymphomas.

To study the role of class II MHC expression in mouse lymphomagenesis, we examined the cell surface expression of I-A/E antigens on 24 spontaneous or murine leukemia virus (MuLV)-induced mouse B10.A (I-Ak, I-Ek) B cell lymphomas. Two primary B10.A B cell lymphomas were observed with strong I-Ek expression but with only minimal cell surface I-Ak expression. Both tumors are readily transplantable in syngeneic mice, with maintenance of their I-A-, I-E+ phenotype. Strikingly, one I-A-, I-E+ B cell lymphoma contains a (11; 17) translocation with a breakpoint on chromosome 17 that is localized within or very close to the H-2 complex. DNA of both tumors contains normal restriction enzyme fragments of the A alpha and A beta genes. Northern blot analyses indicated that one I-A-, I-E+ tumor strongly expressed A alpha, E alpha, and E beta mRNAs but possessed only a weak expression of A beta mRNA. The other B cell lymphoma showed A beta, E alpha, and E beta mRNA expression but only minimal A alpha mRNA expression. In 11 primary B10.A B cell lymphomas with a normal I-A+, I-E+ phenotype, no imbalances in A alpha/A beta mRNA levels were observed. The implications of these findings for the role of class II MHC expression in mouse B cell lymphoma-genesis are discussed.

Animals↗
PubMed1986

The cytogenetics of Wilms' tumor.

A close association has been demonstrated between the congenital deletion 11p13 and predisposition to Wilms' tumor. Recent cytogenetic studies on Wilms' tumor cells from normal children strongly suggests that somatic changes in the short arm of chromosome #11 play an important role in the development of this tumor. The application of improved cytogenetic techniques coupled with molecular biologic analysis may help resolve questions regarding the requirement of additional changes (to alterations of 11p13) in order to evoke complete transformation leading to malignancy.

Child↗
PubMed1986

Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood.

To examine whether determination of (1) the copynumber or restriction pattern of certain oncogenes or (2) the mutational activation of the N-ras gene might contribute to the risk classification of acute lymphoblastic leukemia of childhood (ALL), we investigated DNA isolated from lymphoblasts of untreated patients. Restriction enzyme analysis of cellular oncogenes was performed on DNA of 25 patients. No rearrangements could be demonstrated within or near the genes c-myc, c-myb, c-abl, bcr, c-Ki-ras, and N-ras. No amplifications of these genes nor of N-myc or c-Ha-ras were present. Eight of 21 patients were heterozygote for "rare" Ha-ras allelic restriction fragments that have been associated with an increased risk of developing a malignancy. These patients were clinically indistinguishable from patients lacking these fragments. The breakpoint cluster region (bcr) that is rearranged in all patients with Philadelphia chromosome positive chronic myeloid leukemia, was normal in all cases, including at least one patient with Philadelphia chromosome positive ALL. A 2.8 kb HindIII fragment of a hitherto unknown gene or pseudogene related to v-myb probably derives from the Y chromosome. Nineteen patients were examined for point mutations in the N-ras gene, using a novel synthetic oligonucleotide hybridization assay. In two patients activating point mutations were present, both in positions 1 of the 12th codon. Both patients were somewhat older than the others (16 and 11 years), had L2 morphology, and were shown to have high growth fractions of tumor in their bone marrow.

Adolescent↗
PubMed1985

A cytogenetic study of Wilms' tumor.

Cytogenetic studies were attempted on a sample of 33 Wilms' tumors using short- and long-term tissue culture techniques; most were studied after 2-13 wk in vitro. Abnormal karyotypes were found in 11 tumors, 10 of which had been treated previously with radiotherapy and/or chemotherapy. Insufficient growth of 17 tumors prevented cytogenetic analysis, and in 5 only normal karyotypes were found. Of the 11 tumors with abnormalities, 9 had modes within the diploid range, 1 was hypertriploid, and 1 showed hypodiploid variation. Except for chromosome #5, all chromosomes were involved in structural and numeric changes. Three tumors showed variation in the short arm of chromosome #11, and abnormalities of chromosomes #1, #3, #7, #9, #10, and #14 occurred in more than one tumor. A predisposition to Wilms' tumor is associated with a constitutional deletion of 11p13. From the present study, it is apparent that a similar cytogenetic change may play a primary role in the development of Wilms' tumor in normal individuals.

Cells, Cultured↗