Biomedical subjects
Publications and source records attributed to Michelle Miller.
While newly recognized neck masses in children previously treated for malignancy raise the specter of recurrent disease, recent experience with 2 patients has shown us that enlargement of cervical thymic tissue should be considered in the differential diagnosis, especially early after the completion of chemotherapy or immunotherapy.
About 99% of soil microorganisms are unculturable. However, advances in molecular biology techniques allow for the analysis of living microorganisms. With the advent of new technologies and the optimization of previous methods, various approaches to studying gene expression are expanding the field of microbiology and molecular biology. Methods used for RNA extraction, DNA microarrays, real-time PCR, competitive RT-PCR, stable isotope probing and the use of reporter genes provide methods for detecting and quantifying gene expression. Through the use of these methods, researchers can study the influence of soil environmental factors such as nutrients, oxygen status, pH, pollutants, agro-chemicals, moisture and temperature on gene expression and some of the mechanisms involved in the responses of cells to their environment. This review will also address information gaps in bacterial gene expression in soil and possible future research to develop an understanding of microbial activities in soil environments.
Fibronectin is an extracellular matrix protein with broad binding specificity to cell surface receptors, integrins. The tenth fibronectin type III domain (FNfn10) is a small, autonomous domain of fibronectin containing the RGE sequence that is directly involved in integrin binding. However, in isolation FNfn10 only weakly bind to integrins. We reasoned that high-affinity and high-specificity variants of FNfn10 to a particular integrin could be engineered by optimizing residues surrounding the integrin-binding RGD sequence in the flexible FG loop. Affinity maturation of FNfn10 to alphavbeta3 integrin, an integrin up-regulated in angiogenic endothelial cells and in some metastatic tumor cells, yielded alphavbeta3-binding FNfn10 mutants with a novel RGDWXE consensus sequence. We characterized one of the RGDWXE-modified clones, FNfn10-3JCLI4, as purified protein. FNfn10-3JCLI4 binds with high affinity and specificity to purified alphavbeta3 integrin. Alanine scanning mutagenesis suggested that both the tryptophan and glutamic acid residues following the RGD sequence are required for maximal affinity and specificity for alphavbeta3. FNfn10-3JCLI4 specifically stained alphavbeta3-positive cells as detected with flow cytometry and it inhibited alphavbeta3-dependent cell adhesion. As with the anti-alphavbeta3 antibody LM609, FNfn10-3JCLI4 can interfere with in vitro capillary formation. Taken together, these data show that FNfn10-3JCL14 is a specific, high-affinity alphavbeta3-binding protein that can inhibit alphavbeta3-dependent cellular processes similar to an anti-alphavbeta3 monoclonal antibody. These properties, combined with the small, monomeric, cysteine-free and highly stable structure of FNfn10-3JCLI4, may make this protein useful in future applications involving detection and targeting of alphavbeta3-positive cells.
OBJECTIVE: To compare the effect of early discharge and home-based therapy with conventional hospital rehabilitation on patient and caregiver outcomes at 12 months after hip fracture. DESIGN: Randomized controlled trial. SETTING: Acute and subacute care with follow-up in a community setting in Australia. PARTICIPANTS: Sixty-six older adults admitted to acute care after hip fracture who were assessed as needing rehabilitation. INTERVENTIONS: Eligible patients were randomized to either home-based (n=34) or hospital (n=32) rehabilitation. Patients assigned to the home-based group were discharged home within 48 hours of randomization. Patients assigned to hospital rehabilitation received usual care. MAIN OUTCOME MEASURES: Modified Barthel Index (MBI), timed up and go (TUG) test, Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and Caregiver Strain Index. RESULTS: At 12 months, 56 of 66 (85%) participants were available for follow-up assessment. Both groups achieved significant improvements in MBI and TUG test scores. Patients in both groups had a significant decline in the physical score of the SF-36 and there were no differences between groups. Caregivers of patients allocated to receive home-based therapy reported a reduction in burden after 12 months. Over that period, there was a significant reduction in the burden for caregivers of those patients who received home rehabilitation (P=.020). CONCLUSION: For patients who were previously functionally independent and living in the community, early return home with increased involvement of caregivers after hip fracture resulted in similar patient outcomes (home vs hospital) and less caregiver burden at 12 months.
OBJECTIVE: To compare the four-month outcomes of fallers and nonfallers as well as those with slow gait speed in patients with hip fracture successfully discharged back to the community. DESIGN: Prospective study with four-month follow-up data. SETTING: Community sample of survivors of hip fracture who have completed their rehabilitation programme. SUBJECTS: A consecutive sample of 73 community-dwelling, cognitively intact older adults admitted to hospital following a fall-related hip fracture and available to complete a follow-up assessment at four months. MAIN OUTCOME MEASURES: At baseline, data collection consisted of the Modified Barthel Index (MBI), Mini Mental State Examination (MMSE), sociodemographics and medical history. At four months follow-up, data collection consisted of the MBI, London Handicap Scale (LHS), Berg Balance Scale (BBS), a 10-metre timed walk test, Falls Efficacy Scale (FES) and the Activities Balance Confidence (ABC) scale. Participants were also asked to recall if they had fallen in the four months since their fracture. RESULTS: Seventy-three participants had complete data for evaluation. There was minimal disability with a mean MBI of 91.2 but there was some residual handicap with a mean LHS of 0.67. Those who had fallen had lower self-efficacy (FES) and greater handicap (LHS). Those with slower gait speed were more handicapped (LHS), had lower self-efficacy (FES and ABC) and lower balance scores (BBS). CONCLUSIONS: Measuring ADL disability alone loses valuable information in community-dwelling survivors of hip fracture. Falls after hip fracture should be a target for treatment and our data give some weight to the idea of a fall fracture cycle. Gait speed, which may reflect lower limb strength, is also a target for therapeutic interventions. These measures should be included in clinical practice.
PURPOSE: To assess the role of endorectal coil magnetic resonance imaging (MRI) staging for patients undergoing seed implantation (SI) with or without external beam radiotherapy (EBRT). MATERIALS AND METHODS: Between October 1994 and December 1998, 390 patients underwent prostate SI (98% Pd-103, 2% I-125). Seventy-six percent of patients had a prostate serum antigen (PSA) < 10, 17% had PSA of 10-20, and 7% of patients had PSA of > 20. Ten percent of patients had a Gleason score (GS) of 4-5, 54% had GS 6, 29% had GS 7, and 7% had GS >/= 8. Monotherapy was employed in 46% of patients, and the remaining 54% received combined EBRT and SI. Three hundred twenty-seven were staged by high-resolution phased array pelvic coil, or in most cases, an endorectal coil MRI. The MRI findings were used to guide stage-appropriate treatment recommendations, and to assist in the preplanning and optimization of seed distributions. The criteria utilized to determine MRI-based stage were founded on the reported literature from the University of Pennsylvania. All MRI studies were reviewed by C.A., D.B., or W.H., who were unaware of clinical stage at the time of their review. The biopsy report was available to them as the only clinical correlate. RESULTS: Of the 327 patients staged by MRI, 70% were upstaged from the digital rectal examination-based clinical stage; 26% of T(1), T(2) patients were upstaged to T(3). Perineural invasion and the percentage of positive cores predicted for T(3) MRI stage (p < 0.0001 for both variables). MRI findings changed the overall treatment recommendation in 60/327 (18%) patients. The majority of these patients were advised to receive combined therapy instead of monotherapy after the MRI documented more extensive disease. The seed distribution was modified in 183/327 (56%) patients, mostly related to preplanned extracapsular coverage of bulky or extraprostatic disease seen on MRI. With a mean follow-up of 38 months (range 3-72), PSA freedom from progression (FFP) was 94% at 5 years. Cox regression analysis showed that only the percentage of positive cores (p = 0.001) and failure to have MRI staging (p = 0.0008) predicted for failure. Pretreatment PSA level, Gleason score, perineural invasion, and external beam radiotherapy did not significantly predict for PSA failure. We compared our MRI T(3) intermediate-risk group patients treated by combined therapy with a previous study of T(3) intermediate-risk group treated by radical prostatectomy (RP) at the University of Pennsylvania. Our 36-month PSA FFP was 94% compared with 21% for the previous study's RP patients. CONCLUSION: MRI is a valuable staging procedure for prostate cancer patients treated by SI. PSA FFP results appear to be improved by MRI staging. MRI T(3) disease can be treated more effectively by SI + EBRT than by RP.