Vaccine liability and safety: a progress report.
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Biomedical subjects
Publications and source records attributed to G Evans.
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BACKGROUND AND PURPOSE: B-mode ultrasound imaging affords the opportunity to quantify both intimal-medial thickness (IMT) and lumen diameter of extracranial carotid arteries in ambulatory populations. Since the relation of IMT to lumen diameter may be complex, we asked whether cardiovascular disease risk factors (previously shown to be associated with greater arterial IMT) are related to smaller lumen diameters. METHODS: We used B-mode ultrasound to quantify lumen diameter, interadventitial diameter, and IMT of the extracranial carotid arteries and assessed the relationship of these measures to body mass index, smoking, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, hypertension, and diabetes in 6088 male and 7493 female participants in the Atherosclerosis Risk in Communities (ARIC) cohort. RESULTS: Smoking, hypertension, and LDL cholesterol were consistently related to greater IMT in the common and internal carotid arteries of men and women, as has been previously reported. In the internal carotid artery, smoking, hypertension, and LDL cholesterol were consistently related to smaller lumens. In the common carotid artery, body mass index, smoking, and hypertension were related to significantly larger, and LDL cholesterol to smaller, lumens. Thus, only LDL cholesterol was consistently associated with smaller lumens in both the common and internal carotid arteries. CONCLUSIONS: Risk factors relate positively to IMT in both the common and internal carotid arteries and inversely with lumen diameter in the internal carotid artery, in parallel with their relation to clinical events. However, their association with lumen diameters of the common carotid artery in population-based samples is more complex, and in some cases adverse levels of risk factors may be associated with larger lumens.
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Peripheral blood monocytes respond to interleukin-2 (lL-2) and express the gamma common (gamma c) subunit of the lL-2 receptor (lL-2R) complex. However, the role of lL-2 in myeloid development has recently become of interest for several reasons, including the effect gamma c mutations may or may not have on myeloid development in patients with XSCID. Many studies of lL-2 function in the myeloid cell lineage have been performed on a murine background. To study gamma c expression and function in human myeloid precursors, we introduced the human myelomonocytic cell line, Tf-1, with a retroviral vector containing the human lL-2R beta subunit to create functional human intermediate lL-2R consisting of beta gamma c dimers. We have characterized this transfected variant of Tf-1 (Tf-1 beta) with regard to its response to lL-2. Unlike the parental Tf-1 cell line that is deficient in both lL-2R alpha and lL-2R beta expression, the Tf-1 beta transfectant binds and responds to lL-2 through intermediate-affinity lL-2Rs. Scatchard analyses indicate the number of intermediate-affinity receptors on Tf-1 beta is similar to the number found on the well-characterized YT cell line. However, detection of gamma c on Tf-1 beta cells is dramatically less than on YT cells by Western blot analysis and is undetectable by flow cytometric studies and surface iodinations. The gamma c component on YT cells is readily detected by all three methods. We conclude from these studies that the intermediate-affinity lL-2Rs on the Tf-1 cell line behave differently than those on YT cells with respect to gamma c detection. Either the gamma c molecule itself is different, or the cellular environment in which it functions is altered. Elucidation of gamma c function on this cell line will allow for its use as a model in which other cytokines using gamma c (including lL-2, lL-4, and lL-15) can be studied on the same cellular background.
Eleven novel mutations were identified in the NF2 tumour suppressor gene in a panel of British NF2 patients. Screening was performed using a combination of heteroduplex and single-strand conformation polymorphism analysis on polymerase chain reaction amplified material.
The post-thaw survival and fertility of ram spermatozoa frozen in pellets, 0.25- and 0.5-ml PVC straws, and 0.25-ml minitubes were examined. In 5 experiments, a freezing height of 6 cm above the level of liquid nitrogen was optimal for 0.25- and 0.5-ml straws, whereas 4 cm was best for the 0.25-ml minitubes. Post-thaw motility of spermatozoa was lower for semen frozen in straws and minitubes than in pellets (Experiment 1: 43.7 vs 53.4%, P < 0.001), but after freezing was better in 0.5-ml straws and 0.25-ml minitubes than in 0.25-ml straws (Experiment 1: 44.9 vs 41.3%, P < 0.05; Experiment 2: 49.6 vs 46.8%, P < 0.01). Sperm motility was also better for 1:8 (semen:diluent) pre-freezing dilution rate (50.5%) than for 1:4 (45.6%, P < 0.01) and 1:2 (39.8%, P < 0.001) but not the 1:16 (49.5%) dilution rate. Dry ice was a better freezing medium than liquid nitrogen vapor (49.2 vs 46.9% motile spermatozoa, P < 0.001). The post-thaw motility of spermatozoa was similar for the three freezing packages if the semen was loaded at 5 degrees C, but motility was poorer for semen loaded into 0.25-ml straws than 0.25-ml minitubes at 30 degrees C (P < 0.05). In a fertility test, pregnancy rates were influenced by rams (3 rams, P < 0.05) and freezing package (pellets vs 0.25-ml minitube vs 0.25-ml straw vs 0.5-ml straw, P < 0.05) but not freezing medium (liquid nitrogen vapor vs dry ice). More ewes were pregnant after insemination with pellet-frozen semen (106/150, 71%) than with semen frozen in 0.25-ml straws (85/150, 57%; P < 0.05) and in 0.5-ml straws (83/150, 55%; P < 0.01) but not minitubes (98/150, 65%). It was concluded that minitubes provide a useful alternative to pellets as a storage package for ram spermatozoa, allowing for individual dose identification and easier storage while maintaining a fertility rate indistinguishable from that obtained with pellet-frozen semen.
Because of a predilection for occurrence in the anterior jaw in association with an unerupted tooth, the odontogenic adenomatoid tumor (OAT) will sometimes be discovered in the context of an orthodontic procedure to promote and guide eruption of the tooth. Two cases illustrate this situation. Some other lesions that might have a clinical presentation similar to the OAT are named.
Mutations in the BRCA1 gene, discovered in 1994, are associated with an 80-90% lifetime risk of breast cancer. We have analysed 60 families with a history of breast and/or ovarian cancer for germline mutations in BRCA1. Twenty-two different mutations were detected in 32 families (53%), of which 14 are previously unreported. We observed a significant correlation between the location of the mutation in the gene and the ratio of breast to ovarian cancer incidence within each family. Our data suggest a transition in risk such that mutations in the 3' third of the gene are associated with a lower proportion of ovarian cancer. Haplotype analysis supports previous data which suggest some BRCA1 mutation carriers have common ancestors; however, we have found at least two examples where recurrent mutations appear to have arisen independently.
The motility, acrosome integrity and fertility of ram spermatozoa were examined after treatment with five compounds (caffeine, pentoxifylline, cAMP, 2-deoxyadenosine and kallikrein). Semen was extended with a Tris-based medium and frozen in pellet form. The compounds were added at various concentrations to the semen before freezing or after thawing. Motility and acrosome characteristics were assessed over a 6-h post-thaw period of incubation at 37 degrees C. Of the five compounds examined, only pentoxifylline, when added after thawing, stimulated motility but had not effect on the acrosome integrity of spermatozoa. Pregnancy rates for ewes inseminated in the uterus with semen treated after thawing with Dulbecco's phosphate-buffered saline (PBS, control) or PBS containing pentoxifylline (15 mM in the thawed semen), were 16/39 (41%) and 22/42 (52%) respectively. Motility characteristics of spermatozoa assessed by image analysis (Hamilton-Thorne analyser) were initially better after treatment of thawed semen with pentoxifylline than with PBS ("percent motility', "percent progressive motility', "percent rapid', "percent moderate' and "percent static', P < 0.01 or P < 0.001), but there was a greater deterioration in these characteristics during post-thaw incubation in semen treated with pentoxifylline than in the controls. The deterioration in motility characteristics occurred within 4 h of thawing and this may have been responsible for the modest improvement in fertility of spermatozoa treated with pentoxifylline.
The incidence of postoperative abdominal bulge, hernia, and the ability to do sit-ups was reviewed in a series of 268 patients who had undergone free TRAM (FTRAM) or conventional TRAM (CTRAM) flap breast reconstruction. Minimum follow-up was 6 months. Patients were divided into four groups: unilateral FTRAM (FT1P; n = 123), double-pedicle bilateral FTRAM (FT2P; n = 45), single-pedicle CTRAM (CT1P; n = 40), and double-pedicle or bilateral CTRAM (CT2P; n = 60). The incidence of abdominal bulges (3.8 percent) and hernia (2.6 percent) was similar in the four groups. Synthetic mesh, however, was required for reinforcement of donor site closure twice as often in the CTRAM patients. The ability to perform sit-ups was greatest in the FT1P group (63.0 percent), slightly lower in the CT1P group (57.1 percent), still lower in the FT2P group (46.2 percent), and lowest in the CT2P group (27.1 percent; p = 0.0005). Patients reconstructed with an FTRAM flap were more likely to be able to do sit-ups (58.3 percent) than were those reconstructed with a CTRAM flap (38.2 percent; p = 0.0074). Patients who had only one muscle pedicle used were more likely to be able to do sit-ups (61.7 percent) than were those who had two muscle pedicles used (35.6 percent; p = 0.0003). We conclude that the incidence of abdominal bulge or hernia is relatively independent of the type of TRAM flap used and the number of muscle pedicles harvested. On the other hand, postoperative abdominal strength, as measured by the ability do sit-ups, is influenced significantly by both of these factors.
A weighted scoring system (Dental Panoramic Radiograph Score) taking into consideration the nature, extent, and site of osseous and dental changes on dental panoramic radiographs in familial adenomatous polyposis is described. The weighting takes into consideration the incidence of the anomaly in the general population. The reliability of the system was tested by application to 85 people known to be affected by clinical or mutation analysis, 30 people lacking mutation in the adenomatous polyposis gene, and 19 people shown to be at low risk (< 1%) by linkage analysis. Using the highest thresholds, a specificity of 100% and sensitivity of approximately 68% was obtained. If all positive findings were considered as significant, sensitivity was increased to approximately 82% but the specificity was reduced to approximately 88%. Significant DPRS findings were observed at a significantly higher frequency in patients aged over 20 compared to the patients aged 20 and under. Overall, approximately 68% of the affected subjects had significant changes, and approximately 18% had normal appearance on DPR, with the remainder having changes classified as minimal or equivocal.
The authors examined change in cerebral metabolic function over time by using PET in HIV-infected individuals diagnosed with AIDS. Ten subjects with AIDS received [18F]2-fluoro-2-deoxy-D-glucose PET scans and completed a comprehensive neuropsychological battery. The scan and test battery were repeated after 6 months. Over time, the subjects showed increased relative basal ganglia metabolism as well as increased parietal lobe metabolism. There were no statistically significant changes in neuropsychological performance. These results suggest that PET may be more sensitive than traditional neuropsychological evaluation to subtle central nervous system changes in AIDS.
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Rearrangements of the human trithorax gene (MLL, HRX, Htrx-1, All-1) were studied by Southern blotting in blast cells stored at presentation from 65 adults with de novo acute myelomonocytic (AML-M4) and acute monocytic leukemia (AML-M5). MLL rearrangements were demonstrated in 15 (23%) cases, including eight patients in whom karyotype analysis had failed to detect abnormalities of chromosome band 11q23. The patients with MLL rearrangements did not differ significantly from those with germline configurations in terms of the sex and age of the patients, the presence of lymphadenopathy, hepatosplenomegaly, or central nervous system involvement, and the absolute blast count at diagnosis. Kaplan-Meier analysis of the treated patients demonstrated no difference in survival for patients with MLL rearrangements compared with those without rearrangements. Therefore, in contrast to infantile acute leukemia, in adults with AML-M4 and AML-M5, MLL rearrangements do not identify a subgroup of patients with different clinical features or prognosis.
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