Biomedical subjects
M Grace
Publications and source records attributed to M Grace.
Biochemical and molecular diagnosis of lipoamide dehydrogenase deficiency in a North American Ashkenazi Jewish family.
A late-onset presentation of lipoamide dehydrogenase (E3) deficiency is described in a North American Ashkenazi Jewish (AJ) family. Diagnosis was made by urine organic acid and molecular analyses.
Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by hepatic arterial infusion in a Phase 1 colorectal cancer trial.
The major focus of intrahepatic arterial (IHA) administration of adenoviruses (Ad) has been on safety. Currently, there is little published data on the biological responses to Ad when administered via this route. As part of a Phase I study, we evaluated biological responses to a replication-defective adenovirus encoding the p53 transgene (SCH 58500) when administered by hepatic arterial infusion to patients with primarily colorectal cancer metastatic to the liver. In analyzing biological responses to the Ad vector, we found that both total and neutralizing Ad antibodies increased weeks after SCH 58500 infusion. The fold increase in antibody titers was not dependent on SCH 58500 dosage. The proinflammatory cytokine interleukin-6 (IL-6) transiently peaked within 6 h of dosing. The cytokine sTNF-R2 showed elevation by 24 h post-treatment, and fold increases were directly related to SCH 58500 doses. Cytokines TNF-alpha, IL-1beta, and sTNF-R1 showed no increased levels over 24 h. Predose antibody levels did not appear to predict transduction, nor did serum Ad neutralizing factor (SNF). Delivery of SCH 58500 to tumor tissue occurred, though we found distribution more predominantly in liver tissues, as opposed to tumors. RT-PCR showed significantly higher expression levels (P<0.0001, ANOVA) for adenovirus type 2 and 5 receptor (CAR) in liver tissues, suggesting a correlation with transduction. Evidence of tumor-specific apoptotic activity was provided by laser scanning cytometry, which determined a coincidence of elevated nuclear p53 protein expression with apoptosis in patient tissue. IHA administration of a replication defective adenovirus is a feasible mode of delivery, allowing for exogenous transfer of the p53 gene into target tissues, with evidence of functional p53. Limited and transient inflammatory responses to the drug occurred, but pre-existing immunity to Ad did not preclude SCH 58500 delivery.
Dentist on TV.
Why is it that dentistry just doesn't seem to cut the mustard when the programme planners are looking to fill next year's schedules?
An IMRT dose distribution study using commercial verification software.
The introduction of IMRT requires users to confirm that the isodose distributions and relative doses calculated by their planning system match the doses delivered by their linear accelerators. To this end the commercially available software, VeriSoft (PTW-Freiburg, Germany) was trialled to determine if the tools and functions it offered would be of benefit to this process. The CMS XiO (Computerized Medical System, St. Louis, MO) treatment planning system was used to generate IMRT plans that were delivered with an upgraded Elekta SL15 linac. Kodak EDR2 film sandwiched in RW3 solid water (PTW-Freiburg, Germany) was used to measure the IMRT fields delivered with 6 MV photons. The isodose and profiles measured with the film generally agreed to within +/- 3% or +/- 3 mm with the planned doses, in some regions (outside the field) the match fell to within +/- 5%. The isodose distributions of the planning system and the film could be compared on screen, allowing for electronic records of the comparison to be kept if desired. The features of this software would be of benefit to an IMRT QA program.
Pelvic organ descent in young nulligravid women.
OBJECTIVE: There is little information available on what constitutes "normal" pelvic organ mobility. This study presents normal values for urethral, bladder, cervical, and rectal descent on Valsalva. STUDY DESIGN: One hundred eighteen nulligravid white women aged 18 to 24 years were recruited for a prospective observational study. Translabial ultrasound was undertaken supine and after voiding, with the most effective of at least 3 Valsalva maneuvers used for evaluation. RESULTS: Urethral rotation on Valsalva varied from 0 to +90 degrees (mean 32 degrees), bladder neck descent from 1.2 to 40.2 mm (mean 17.4 mm). The cervix descended to between 59 and 0 mm above the symphysis pubis (mean 30.8 mm); the rectal ampulla descended to between 54 mm above and 22 mm below the symphyseal margin (mean 7.8 mm). In a test-retest series, intraclass correlations were between 0.64 and 0.89, implying good-to-excellent repeatability of the ultrasound assessment. CONCLUSION: A wide range of values was obtained for all parameters. A significant congenital contribution to the phenotype of female pelvic organ prolapse appears likely.
ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency.
T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4+ T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4+ T cells, and delayed disease progression following intrarectal challenge exposure of the animals to SIV(mac251 (561)). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8+ T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in Mamu-A*01-positive macaques following intravenous challenge with either SIV(mac251 (561)) or SIV(SME660). However, a significant delay in CD4+ T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV(89.6P) or SHIV(KU2), respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models.
Is CPD effective?
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Biological activities and molecular targets of the human papillomavirus E7 oncoprotein.
The human papillomavirus (HPV) E7 protein is one of only two viral proteins that remain expressed in HPV-associated human cancers. HPV E7 proteins share structural and functional similarities with oncoproteins encoded by other small DNA tumor viruses such as adenovirus E1A and SV40 large tumor antigen. The HPV E7 protein plays an important role in the viral life cycle by subverting the tight link between cellular differentiation and proliferation in normal epithelium, thus allowing the virus to replicate in differentiating epithelial cells that would have normally withdrawn from the cell division cycle. The transforming activities of E7 largely reflect this important function.
How much does it cost?
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I'll be alright, Jack.
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Just for the record. . .
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Opportunities for women.
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The training plan.
A training plan needs to be a working document that helps ensure the appropriate training for everyone in the organization is carried out.
Learning styles.
Before we can draw up our plan we need to first look at learning itself, and be aware that a number of different learning styles exist which can influence our choice of appropriate training.