Associated soft tissue injuries.
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Contusions↗
Biomedical subjects
J Bennett
Publications and source records attributed to J Bennett.
Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses.
Expression of P-glycoprotein (Pgp), the product of the multidrug resistance (MDR1) gene, detected by flow cytometric analysis of the binding of antibody 4E3.16, was found on significantly fewer leukemic cells in 35 adult patients with de novo acute promyelocytic leukemia (APL) (mean 14.8%, median 7%) than in 184 patients with non-APL acute myeloid leukemia (AML) at diagnosis (mean 28.3%, median 18%) (p = 0.0038). APL was diagnosed based on morphology, the detection of t(15;17) and of the chimeric fusion transcript PML/RAR alpha by PCR. To further substantiate low MDR1 expression in APL, we studied cells from 11 APL patients at the molecular and functional level in comparison to 48 non-APL cases. The diagnosis of APL was associated with the absence of Pgp function by the rhodamine efflux assay (p = 0.0001). Furthermore, MDR1-specific transcript levels, determined by quantitative PCR with two distinct sets of primers, were significantly lower in mononuclear cells from the APL than the other AML cases (p = 0.013). The frequency of leukemic cells positive for CD34, an antigen presumably associated with Pgp expression in AML, was significantly lower in APL than other AMLs (p = 0.0001). In contrast to non-APL leukemias, those few cases of CD34 strongly positive APL neither expressed Pgp nor contained significant MDR1 transcript levels. Low expression of Pgp by APL cells may provide the biologic basis for the high sensitivity of this leukemia subtype to chemotherapeutic agents in vivo.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Sex-specific differences in mortality after high-titre measles immunization in rural Senegal.
Administration of high-titre measles vaccine (Edmonston-Zagreb (EZ) at > 10(5) plaque-forming units (PFU) per dose) before the age of 9 months has been recommended in areas with high measles mortality before the routine age of immunization after 9 months. The study compares the long-term survival after high-titre measles immunization at 5 months of age with that following routine immunization with standard-titre vaccine at 10 months of age. At 5 months of age the high-titre group received Edmonston-Zagreb (EZ-HT, 5 months) or Schwarz (SW-HT, 5 months) at titres > 10(5) PFU per dose, while the standard-titre group received placebo at 5 months of age and < 10(4) PFU per dose of Schwarz vaccine at 10 months (SW-std, 10 months). All the children were followed up to at least 36 months of age. The mortality ratio (MR) for infants in the EZ-HT, 5 months and SW-HT, 5 months groups was 1.32 (P = 0.089) and 1.45 (P = 0.092), respectively, which did not differ significantly from that of recipients of the SW-std, 10 months. The higher MR among recipients of the high-titre vaccines was due to the significantly lower survival among females compared with the females who received SW-std vaccine (EZ-HT, 5 months MR = 1.76, P = 0.013; SW-HT, 5 months MR = 2.14, P = 0.017). For children aged 5-10 months the high-titre measles vaccine did not increase mortality relative to unvaccinated children who had received placebo.
Bias↗
The immunophenotype of acute promyelocytic leukemia (APL): an ECOG study.
In 452 adult patients with de novo acute myeloid leukemia (AML), a series of 22 monoclonal antibodies was used to identify immunophenotypic characteristics of acute promyelocytic leukemia (APL) as compared to other AMLs (groups FAB M1/M2 and M4/M5). Only those patients with FAB M3 cytology were included in the analysis for which APL was confirmed by the presence of the t(15;17) cytogenetic aberration and the detection of the PML/RAR alpha gene fusion transcript by PCR amplification (35 cases). Significantly fewer APL blast cells were positive for the stem cell antigen, CD34 (p = 0.0001) as well as for HLA-DR (p < 0.0001). With respect to myeloid antigens, APLs less frequently expressed the myelomonocytic antigens, CD11b (p = 0.0001) and CD14 (p = 0.0013), whereas expression of CD33, a pan-myeloid marker, was more frequent in APL (p = 0.0001). CD15, the X-hapten carbohydrate structure (lacto-N-fucopentaose-III), typically expressed at the maturation stage of normal promyelocytes, was found to be sialylated on APL blasts as recognized by differential binding of the anti-CD15 antibodies, VIM-D5 (non-sialylated CD15) and VEP-9 (sialylated CD15). Expression of the T-cell associated CD7 antigen was rarer on APL than non-APL cells (p = 0.0001), as was that of the multidrug resistance P-glycoprotein (p = 0.0038). Marginal correlations existed between antigen profile (particularly CD2) and the type of PML/RAR alpha transcripts. In addition to its unique genotypic features, these data establish APL as a distinct immunophenotypic entity.
Adult↗
Adenovirus vector-mediated in vivo gene transfer into adult murine retina.
PURPOSE: To determine whether a reporter gene can be introduced into the adult mammalian retina in vivo through means of a recombinant replication-deficient adenovirus. METHODS: A dilution series of purified Ad.CMVlacZ ranging from 10(5) to 10(11) pfu/ml was prepared and microinjected into the subretinal space of adult CD-1 mice. This virus contained the cytomegalovirus (CMV)-promoted Escherichia coli reporter gene, lacZ. LacZ expression was assessed in enucleated eyes from 0 to 95 days after injection by beta-galactosidase (beta-Gal) assay. RESULTS: The efficiency of transfection increased as a function of concentration of recombinant virus injected. Eyes injected with greater than 10(7) pfu of Ad.CMVlacZ demonstrated beta-Gal activity lasting at least 95 days. LacZ expression was apparent only in those cells directly exposed to the adenovirus. LacZ expression was observed in the retinal pigment epithelium (RPE) at high efficiency at 48 hours after exposure. By 2 weeks after injection of > 10(7) pfu, lacZ was also expressed in photoreceptors, but at lower density. CONCLUSIONS: These results demonstrate that high efficiency stable transfer of functional genes can be achieved in vivo in post-mitotic mammalian retina using recombinant adenoviral vectors. Adenovirus vectors appear to be a promising means for delivering therapeutic genes in vivo to the mammalian neural retina and particularly to the RPE.
Adenoviruses, Human↗
Assessment of praziquantel therapy in treatment of Schistosoma mansoni infection.
The present study is the first report of the epidemiological survey carried out as a part of the Praziquantel resistance project which is one of the projects of Schistosomiasis Research Project (SRP) in Egypt. The results of the study, which has been carried out in 3 villages, revealed that praziquantel is effective as an antischistosomal drugs and reduced egg count significantly. However at the end of the study some cases remained infected in spite of the three treatment regimens. Several factors can be responsible, among them is the presence of resistance strains, which will only be elucidated in the subsequent steps of the project, when identification of resistant strains in experimental animals will be carried out.
Drug Resistance↗
Divergent mortality for male and female recipients of low-titer and high-titer measles vaccines in rural Senegal.
The female/male mortality ratio among unimmunized children and children vaccinated with standard or high-titer measles vaccines was examined for all children born in the period 1985-1991 in a rural area of Senegal. The female/male mortality ratio from 9 months to 5 years of age for unvaccinated children was 0.94 (95% confidence interval (CI) 0.75-1.19), significantly different from the ratio of 0.64 (95% CI 0.48-0.85) for recipients of the Schwarz standard measles vaccine (p = 0.040). In the 4-year period, where high-titer measles vaccines were used in the study area, the female/male mortality ratio was 1.33 (95% CI 1.00-1.78) for recipients of high-titer Edmonston-Zagreb or Schwarz vaccines compared with 0.67 (95% CI 0.42-1.07) for recipients of the Schwarz standard vaccine (p = 0.013). Hence, the Schwarz standard and high-titer measles vaccines have divergent sex-specific effects on mortality throughout childhood. Further studies of the underlying mechanisms are needed.
Cause of Death↗
Acute myeloid leukemia M4 with inv(16) (p13q22) exhibits a specific immunophenotype with CD2 expression.
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Antigens, Differentiation, T-Lymphocyte↗
Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia.
A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1 beta genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1 beta gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy.
Aged↗
Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study.
In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine. Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate.
Adult↗
Preliminary characterization of porcine bone marrow stromal cells: skeletogenic potential, colony-forming activity, and response to dexamethasone, transforming growth factor beta, and basic fibroblast growth factor.
Neonatal pig bone marrow stromal cells (PBMSC) were tested in vivo and in vitro to establish their use as a large-animal model for the study of skeletogenesis. When implanted in diffusion chambers in athymic mice for 6-8 weeks, both freshly isolated pig bone marrow and passage 2 PBMSC formed partially mineralized cartilage, bone-like material, and fibrous tissue. The cartilage showed metachromatic, perilacunar staining with toluidine blue and safronin O, alcian blue staining for chondroitin and keratan sulfate, and intense immunostaining for type II collagen. Osteocalcin was immunolocalized to the mineralized regions, consistent with the formation of bone. Alkaline phosphatase was primarily observed in cell layers at boundaries between tissue types. Unstimulated monolayer cultures of PBMSC produced type I but not type II collagen, responded to dexamethasone (10(-8) M) with a 1.7-fold increase in alkaline phosphatase activity, and were stimulated to divide by basic fibroblast growth factor (1.5-fold; EC50 1 ng/ml). Transforming growth factor beta (TGF-beta) blocked both dexamethasone-induced alkaline phosphatase expression (EC50, 1 ng/ml of TGF-beta) and the mitogenic effects of bFGF (EC50 0.06 ng/ml of TGF-beta). When incubated for 10-14 days in medium containing dexamethasone, beta-glycerophosphate and ascorbate PBMSC formed mineralized nodules. Calcification occurred in the middle of the aggregates and was associated with intensely alkaline phosphatase positive cells and a dense type I collagen-rich matrix. PBMSC also displayed colony-forming unit-fibroblastic activity, with approximately 1 in 80 of the plated cells formed colonies > 128 cells over 14-21 days. PBMSC therefore mimic the known activities of stromal cells from other species, including the human, suggesting that they are a valid model for skeletal research.
Alkaline Phosphatase↗
Genes for crop improvement.
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Base Sequence↗
Improving decision making at school entry medicals--completing the audit cycle.
An audit of decision making at the entry medical was carried out to ascertain how doctors responded to childrens' physical, developmental and psychosocial adversity. Using specifically designed recording protocols, eleven doctors recorded their activity at 922 entry medicals over one term. The results were discussed, protocols of decision making were prepared and ten doctors re-ran the exercise assessing a further 783 over one term; one year later. The proportions discussed with headteachers, referred to agencies and selected for review varied in both data sets, and certain trends emerged. More experienced doctors were more likely to discuss vulnerabilities and did so for 18 to 25% of entrants in addition to the 20-30% referred or selected for review. The introduction of guidelines increased the overall proportion of children discussed with teachers and reduced, in part, the proportion scheduled for review. This study informs the debate about selective entry medicals. The findings will be of interest to commissioners of health care who have the responsibility for contracting for school entry assessments.
Child↗
Effect of extradural diamorphine on analgesia after caesarean section under subarachnoid block.
We have examined the efficacy, duration of action and side effects of extradural diamorphine alone and in combination with 1:200,000 adrenaline in a randomized, double-blind controlled study of 45 patients who underwent Caesarean section under spinal anaesthesia. Saline 10 ml, diamorphine 2.5 mg in saline 10 ml or diamorphine 2.5 mg in 1:200,000 adrenaline 10 ml were administered via the extradural route at delivery of the baby. Both diamorphine and diamorphine with adrenaline provided significantly prolonged analgesia compared with control (mean time to next analgesia (95% confidence interval) 17.3 h (12.0, 22.1 h), 15.9 h (10.6, 21.1 h), 5.7 h (1.5, 9.9 h), respectively) (P < 0.01). The addition of adrenaline increased the quality of analgesia 8 h after operation, but had no effect on the total amount of i.m. morphine administered during the first 24 h. The incidence of side effects was similar in all groups.
Adult↗
Resistance of a human serum-selected human immunodeficiency virus type 1 escape mutant to neutralization by CD4 binding site monoclonal antibodies is conferred by a single amino acid change in gp120.
We have selected an HXB2 variant which can replicate in the presence of a neutralizing human serum. Sequencing of the gp120 region of the env gene from the variant and parental viruses identified a single amino acid substitution in the third conserved region of gp120 at residue 375 (AGT-->AAT, Ser-->Asn; designated 375 S/N). The escape mutant was found to be resistant to neutralization by soluble CD4 (sCD4) and four monoclonal antibodies (MAbs), 39.13g, 1.5e, G13, and 448, binding to epitopes overlapping that of the CD4 binding site (CD4 b.s.). Introduction of the 375 S/N mutation into HXB2 by site-directed mutagenesis confirmed that this mutation is responsible for the neutralization-resistant phenotype. Both sCD4 and three of the CD4 b.s. MAbs (39.13g, 1.5e, and G13) demonstrated reduced binding to the native 375 S/N mutant gp120. The ability to select for an escape variant resistant to multiple independent CD4 b.s. MAbs by a human serum confirms the reports that antibodies to the discontinuous CD4 b.s. are a major component of the group-specific neutralizing activity in human sera.
Amino Acid Sequence↗
The development of alcohol strategies in England and Wales.
Alcohol has become a major public health problem in the UK. In order to coordinate the work of both statutory and non-statutory agencies more efficiently and effectively, a government circular HN(89)4 has emphasized the need for development of local multi-agency alcohol misuse prevention strategies. Despite expressed enthusiasm for alcohol strategies, information about their development, effectiveness and overall national progress is scarce and needs to be improved. This national survey reports the most recent and accurate information about the development of district and regional alcohol strategies in England and Wales. Although only 51 (27%) districts stated they had a strategy, it was encouraging to find 90 (47%) other districts that were in the process of, or planning to develop such a document. Of the 51 districts with a strategy, the following key findings were noted: (1) Forty-three (84%) districts stated that they had started to implement their strategy, but none claimed to have fully implemented it. (2) Thirty-six (71%) districts stated that their strategy had an action plan. (3) Thirty-four (67%) districts stated that their strategy had been officially endorsed by the district health authority. (4) Thirty-eight (76%) districts stated that they had identified an individual or group to monitor the strategies' implementation. The results of the survey could be of interest to the Department of Health, the Faculty of Public Health Medicine, the Health Education Authority and the regional alcohol coordinators.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcoholism↗