Provider automation. Using the Internet to access records.
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Attitude to Computers↗
Biomedical subjects
M A Cross
Publications and source records attributed to M A Cross.
Planning for disaster recovery.
Planning for restoring information systems in the event of a disaster is rapidly changing and growing in importance. As health care organizations become more reliant on information technology, they're taking extra steps to safeguard their investments and to ensure reliable access to data.
Academic Medical Centers↗
Disney's city of the future.
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Community Health Centers↗
Practice management companies. Creating sound information technology strategies.
Practice management companies are becoming more prominent players in the health care industry. To improve the performance of the group practices that they acquire, these companies are striving to use updated information technologies.
Confidentiality↗
Mechanisms of antigenic variation in African trypanosomes.
African trypanosomes can escape destruction by the immune system of their mammalian host by antigenic variation of the trypanosome surface coat. This coat is mainly composed of a single protein species, the Variant Surface Glycoprotein or VSG. The genes for VSGs are expressed in a polycistronic telomeric expression site together with at least eight expression site-associated genes (ESAGs). Trypanosomes may switch coat either by replacing the VSG gene in the active expression site by a different one, or by activating another expression site with concomitant silencing of the previously active one. Here we review our present knowledge of antigenic variation in Trypanosome brucei. We focus on four questions: How do trypanosomes switch from one VSG gene expression site to another one? What is the role of the novel base J in silencing expression sites? What is the functional significance of the antigenic variation of the heterodimeric transferrin receptor encoded by two ESAG genes? Why do trypanosomes have multiple expression sites at all?
Africa↗
The viral thymidine kinase gene as a tool for the study of mutagenesis in Trypanosoma brucei.
We have tested the use of thymidine kinase as a negative selection system for Trypanosoma brucei. To this end we have targeted a construct containing a Herpes simplex virus thymidine kinase (TK) gene into the ribosomal DNA array of procyclic T. brucei. This resulted in TK activity 30-50-fold above background and in susceptibility to the nucleoside analogues ganciclovir, ethyl-deoxyuridine and 1-[2-deoxy,2-fluoro-8-D-arabinofuranosyl]-5-iodouracil, all of which have no effect on wild-type trypanosomes. TK+ trypanosomes, however, reverted to a ganciclovir resistant phenotype at a rate of 10(-6) per cell-generation. A similar reversion rate was observed using the Varicella-zoster virus TK gene. Loss of TK activity was not due to detectable DNA rearrangements or a decrease in TK mRNA. Sequence analysis of the revertant genes demonstrated, however, the occurrence of point mutations and frameshifts. One revertant line had a mutation in the thymidine binding site leading to the substitution of a conserved arginine by a glycine. Other mutations included single base insertion, single base deletion and the introduction of a premature termination codon by point mutation.
Animals↗
Provider as payer. Technology helps manage risk.
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Capitation Fee↗
Dissection of the core and auxiliary sequences in the vegetative replication origin of promiscuous plasmid RK2.
The vegetative replication origin (oriV) of promiscuous IncP plasmid RK2 can function in many Gram-negative bacterial species when supplied with the plasmid-encoded replication protein TrfA and host-encoded replication proteins including DnaA. Nine TrfA binding sites (iterons) are known, and also two DnaA binding sites, box 1, between TrfA iterons 4 and 5, and box 2, downstream of repeat 9. The deletion analysis presented here shows that the core oriV requires DnaA box 1 for function in Escherichia coli and Pseudomonas putida. This DnA box is not essential in Pseudomonas aeruginosa, although its deletion does reduce plasmid copy number in this species. A putative IHF binding site is located upstream of DnaA box 1, but IHF deficiency in E. coli seems not to alter replication efficiency or copy number control. Cloned oriV can interfere with maintenance of an independent RK2 replicon. Analysis of replication inhibition functions associated with oriV showed that a short putative orf between TrfA iterons 1 and 2 is not necessary for replication inhibition, the presence of repeats 5 to 9 in target and inhibitor plasmid are not sufficient for efficient inhibition and inhibition does not correlate directly with the number of direct repeats present. Rather, the results showed that the isolated repeats 1 and 2 to 4, potentiate replication inhibition disproportionately to their effect on the number of TrfA binding sites. The results are consistent with the idea that repeats 1 to 4, arranged as a single copy and as an irregular group of three, potentiate the ability of the oriV region to form complexes which inhibit replication. We suggest that TrfA bound at these iterons may be more susceptible to forming pairs between oriV sequences on different plasmids.
Bacterial Proteins↗
Discordant regulation of SCL/TAL-1 mRNA and protein during erythroid differentiation.
The SCL/TAL1 gene was originally identified by virtue of its rearrangement and transcriptional activation in patients with T cell acute lymphoblastic leukaemia. It encodes a helix-loop-helix transcription factor, is not normally expressed in T cells, but is expressed in erythroid, mast, megakaryocytic and progenitor cells. Over-expression of sense and antisense constructs have implicated SCL as a positive regulator of erythroid differentiation. In addition we have previously shown that SCL mRNA levels undergo biphasic modulation during induced erythroid differentiation of murine erythroleukaemia (MEL) cells with a transient early fall followed by a late rise. In this paper we have studied expression of the SCL protein during erythroid differentiation and also the molecular basis for the raised SCL mRNA levels that accompany erythroid differentiation. We have generated an anti-SCL antiserum and used it to demonstrate that an early transient fall in SCL protein does not occur during induced differentiation of MEL cells. Furthermore SCL protein levels underwent a late fall in three different models of erythroid differentiation and in two models of myeloid differentiation. The fall in SCL protein levels during induced erythroid differentiation contrasted with the concomitant marked rise in SCL mRNA levels. These observations have significant implications for the mechanism by which SCL may regulate erythropoiesis. In addition we have demonstrated that the stability of SCL mRNA was only marginally enhanced during erythroid differentiation of MEL cells, whereas the activity of a luciferase reporter construct driven by the SCL promoter was increased 11- to 17-fold. Up-regulation of transcription therefore accounted for most of the increase in SCL mRNA levels during erythroid differentiation.
Animals↗
Do results justify an aggressive strategy targeting the pedal arteries for limb salvage?.
We initiated a strategy to bypass all of the significant popliteal and tibial disease in the setting of limb-threatening ischemia beginning in September 1986. Of 194 infrapopliteal bypasses performed for limb salvage during the ensuing 6 years, 111 (57%) autogenous vein bypasses were performed to the pedal vessels at or distal to the ankle. By life table analysis, primary graft patency at 60 months for pedal bypasses was 57%, with salvage of failed grafts resulting in secondary patency of 61%. Limb salvage was 64% at 60 months. Of 33 graft thromboses, 24 (73%) resulted in eventual limb loss. Five limbs were amputated due to wound complications or progressive forefoot sepsis despite patent pedal grafts. More bypasses were performed to the dorsalis pedis than the posterior tibial at the ankle (78 vs 33), but patency and limb salvage were similar. Bypasses to the pedal arteries resulted in superior limb salvage compared with peroneal bypass when forefoot tissue necrosis was present (63 vs 33% at 36 months, P = 0.048). Pedal grafts had comparable overall patency (57 vs 64%) and limb salvage (64 vs 75%) to more proximal tibial bypasses. Pedal bypass provides acceptable long-term outcomes for both patency and limb salvage. When forefoot ischemic tissue loss is present, pedal bypass, when feasible, appears preferable to peroneal bypass.
Diabetes Mellitus↗
Erythroid development of the FDCP-Mix A4 multipotent cell line is governed by the relative concentrations of erythropoietin and interleukin 3.
Conditions are described which promote the erythroid development of the FDCP-Mix A4 (A4) cell line with accompanying proliferation of the cells. The requirements for this development are low concentrations of interleukin 3 (IL-3) plus the presence of erythropoietin (epo) and haemin. When high concentrations of IL-3 are added with erythropoietin and haemin the cells do not differentiate and maintain their blast cell morphology. Addition of haemin, in the absence of erythropoietin, does not promote erythroid development, but the presence of haemin with erythropoietin promotes increased proliferation and maturation. The morphological maturation of A4 cells along the erythroid lineage is accompanied by a gradual loss of clonogenic potential, loss of A4 cell multipotency, increased erythropoietin receptor expression, and an increased expression of the beta-globin gene. An initial increase in mitogenic responsiveness to erythropoietin is followed by a decrease as the cells become refractory to all mitogenic stimuli with the acquisition of a postmitotic, mature erythroid cell phenotype.
Blotting, Northern↗
Effect of felodipine treatment and withdrawal on blood pressure and cardiovascular structure in New Zealand genetically hypertensive rats.
1. Four groups of New Zealand genetically hypertensive (GH) rats were treated with felodipine as follows: (A) from ages 4-12 weeks; (B) 4-20 weeks; (C) 4-12 weeks then withdrawn from felodipine till age 20 weeks; and (D) 12-20 weeks. 2. Effects on blood pressure (BP), left ventricular (LV) weight and the structure of myograph-mounted mesenteric resistance arteries (MRA) were measured. 3. BP was about 170 mmHg in 4 week old GH rats and did not change substantially from this value in groups A and B but rose to over 230 mmHg in untreated controls. In rats of group D, started on felodipine at 12 weeks, BP fell rapidly and was 173 mmHg at 20 weeks. On withdrawal of felodipine at 12 weeks (group C) BP rose rapidly and exceeded control levels at 20 weeks. 4. LV mass was significantly lower (P < 0.001) in all groups (A, B and D) killed while on felodipine but rose to control levels in the rats taken off felodipine. 5. In the four treated groups there were no significant changes in MRA structure (lumen diameter, medial thickness, media/lumen ratio and volume of medial tissue) as measured on the myograph. 6. Felodipine induces substantial falls in BP in GH rats which are sufficient to prevent cardiac hypertrophy but do not alter MRA structure. Resistance artery structure in GH rats does not seem to relate to the level of hypertension, and may therefore not have a necessary role in the pathogenesis of this hypertensive strain.
Animals↗
Paterson symposium 1993--gene therapy.
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Genetic Therapy↗
Expression of lineage restricted transcription factors precedes lineage specific differentiation in a multipotent haemopoietic progenitor cell line.
Lineage commitment and differentiation are likely to be coordinated by the combined effects of multiple transcription factors acting on numerous different target genes. The mechanisms by which lineage-restricted patterns of transcription factor expression are established are therefore of particular relevance to our understanding of the role of transcription factors both in normal development and in oncogenesis. Here, we report that the genes for the lineage-restricted transcription factors SCL, GATA-1 and GATA-2 are expressed in all multipotent, IL-3-dependent, haemopoietic progenitor cell lines tested. Moreover, a liquid differentiation assay has been used to demonstrate down regulation of SCL, GATA-1, GATA-2 and PU-1 during differentiation into non-expressing lineages. These data support the concept that multiple lineage-restricted transcription factors are expressed prior to lineage commitment.
Cell Line↗
Ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive irradiation. Correlation of pathologic parameters with outcome of treatment.
BACKGROUND: To evaluate the pathologic characteristics of the primary tumor relative to local control, survival, and freedom from distant metastases, an analysis was performed of 172 patients with ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive breast irradiation. METHODS: The clinical records and pathology slides were reviewed from 172 women with ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation at multiple institutions in Europe and the United States. Central pathology review was performed by one pathologist without knowledge of the clinical outcome. The clinical outcome was measured in terms of local control, overall survival, cause-specific survival, and freedom from distant metastases. The median follow-up time was 84 months (range, 17-177 months). RESULTS: The pathologic parameters evaluated were histologic subtype, nuclear grade, amount of necrosis, and final pathology margin. The only pathologic parameter that correlated with the rate of local recurrence was the presence versus the absence of the combination of the histologic subtype of comedo carcinoma plus nuclear grade 3 (8-year actuarial rate of local recurrence of 20% versus 5%, respectively; P = 0.009 on univariate analysis; P = 0.017 on multivariate analysis). None of the pathologic parameters evaluated correlated with overall survival (all P > or = 0.16), cause-specific survival (all P > or = 0.13), or freedom from distant metastases (all P > or = 0.13). CONCLUSIONS: These results have demonstrated that there are important differences in the rate of local recurrence based on the pathologic characteristics of the primary tumor for women with ductal carcinoma in situ treated with breast-conserving surgery and definitive irradiation. However, the differences in local recurrence have not been associated with differences in survival or freedom from distant metastases. Careful follow-up for patients at increased risk for local recurrence is warranted because of the potential ability to salvage patients with local recurrence.
Adult↗
Limitations of peroneal artery bypass grafting for limb salvage.
PURPOSE: The purpose of this study was to compare the results of peroneal bypass grafting for limb salvage with the results of other tibial and pedal bypass grafts performed concurrently. METHODS: Thirty-four peroneal bypass grafts with autologous vein were performed for limb salvage between September 1986 and June 1992. These constituted 18% of an overall experience of 194 tibial or pedal bypasses performed during that time. Preoperative and intraoperative arteriograms were reviewed to identify anatomic characteristics associated with successful limb salvage. RESULTS: Secondary patency rates for peroneal bypass grafts (70%) compared with the other tibial and pedal bypass grafts (65%) did not differ significantly at 48 months by life-table analysis. Limb salvage achieved by peroneal artery bypass grafting was significantly worse (55%) than that achieved by the remaining tibial and pedal bypasses (67%) at 48 months. Limb salvage was 33% at 7 months for those undergoing peroneal artery bypass grafting as opposed to 57% at 48 months for patients undergoing other tibial or pedal revascularizations with tissue necrosis. Four anatomic features were identified that were associated with failure after peroneal artery bypass grafting. These were peroneal length less than 10 cm (p = 0.012), peroneal artery diameter less than 2 mm (p = 0.035), absence of arteriographically demonstrated collaterals perfusing the foot (p = 0.0001), and little or no visualization of the pedal arch (p = 0.008). CONCLUSIONS: Although successful grafts may avoid amputation in carefully selected cases, alternatives to peroneal artery bypass grafting should be considered when less than favorable anatomic conditions are encountered, particularly in the presence of forefoot tissue necrosis.
Aged↗
Expression and downregulation of cytotoxic cell protease 1 or Granzyme 'B' transcripts during myeloid differentiation of interleukin-3-dependent murine stem cell lines.
Using the technique of differential cDNA library screening, we have molecularly cloned a gene that is highly expressed in an undifferentiated myeloid multipotent and growth factor-dependent stem cell line (FDCP-Mix) and that downregulates as these cells are induced to differentiate along monocytic, granulocytic, and erythroid cell lineages. Sequence analysis of this gene has shown homology with a previously cloned gene, cytotoxic cell protease 1 (CCP1 or Granzyme 'B'), that has been shown to be expressed only in thymocytes, activated T cells, a mast cell line, and peritoneal exudate leukocytes. In situ hybridization, Northern blot analysis, and nuclear run-off assay has confirmed that expression of CCP1 is restricted to the phenotypically primitive multipotent undifferentiated. FDCP-Mix cells that are undergoing self-renewal in the presence of growth factors such as interleukin-3.
Amino Acid Sequence↗
Ten-year results of breast-conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast.
An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10-year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow-up time was 78 months (range, 11 to 197 months). The 10-year actuarial overall survival rate was 94%, and the 10-year actuarial cause-specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10-year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty-four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow-up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node-positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow-up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow-up of patients after breast-conservation and definitive irradiation is required.
Actuarial Analysis↗