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Biomedical subjects

E Chao

Publications and source records attributed to E Chao.

14 recordsLinked to original sources

Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis.

In a 4 year clinical trial in 202 postmenopausal osteoporotic women receiving NaF at 75 mg/day or placebo (both groups received supplementary calcium at 1500 mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral density in the lumbar spine (LS-BMD) substantially but did not decrease vertebral fracture rate (VFR), and it increased the nonvertebral fracture rate. Additional analyses and extended observations are now available on 50 women from the NaF group followed for up to 6 years of treatment. In these women, LS-BMD increased linearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm2/year). Because during the 4 year trial the NaF dosage was decreased (because of side effects) in 54 of the 101 women randomized to NaF, dose-response relationships could be evaluated. For the entire study population, serum F level correlated directly with increase in LS-BMD (r = 0.61, P < 0.001). When individual person-years of observation were grouped by deciles of LS-BMD, VFR (per 100 person-years) decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2 g/cm2 and then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm2. Multivariate analyses and inspection of three-dimensional plots revealed a complex pattern in which VFR was influenced by interaction of several variables. When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed simultaneously, VFR was seen to decrease with increasing LS-BMD except when the higher LS-BMD was associated with rapid rate of increase in LS-BMD or a large increase from baseline serum F. For some patients (noncompliers or nonresponders), serum F or LS-BMD failed to increase. Thus, it is possible that lower dosages of NaF produce moderate decreases in VFR.

Aged

Seasonal variation of vitamin A (retinol) status in older men and women.

OBJECTIVE: The present study was undertaken to determine vitamin A status in 59 free-living (26 males, 33 females) healthy older persons (65-74 years) in winter and summer. DESIGN: Three-day dietary intake data for vitamin A along with carbohydrate, lipid and protein were collected during the summer (June-September) and again during the winter (November-March). In addition, retinol and its carrier proteins, retinol-binding protein (RBP) and transthyretin (TTR), were measured in the plasma in each season. RESULTS: The mean vitamin A intake met the Canadian Recommended Intake (RNI) for both gender and season. However, probability analysis of dietary data revealed that 7 and 11% of males, and 8 and 14% of females, in summer and winter, respectively, were at risk of deficiency. None of the subjects in the present study exhibited biochemical evidence of vitamin A deficiency as determined by plasma levels of retinol and its transport proteins. Overall, the mean intake of vitamin A was significantly higher in males than in females; no seasonal effect was observed. On the other hand, the plasma levels of retinol and its carrier proteins were significantly lower in winter season than in summer, without any gender variation effect. CONCLUSION: Although mean values for dietary intake and plasma concentration of vitamin A may indicate nutritional adequacy, a small proportion of an older population may be at nutritional risk. The prevalence of risk appears to be generally higher in the winter than in the summer season and in females than in males.

Aged

Data explorer: a prototype expert system for statistical analysis.

The inadequate analysis of medical research data, due mainly to the unavailability of local statistical expertise, seriously jeopardizes the quality of new medical knowledge. Data Explorer is a prototype Expert System that builds on the versatility and power of existing statistical software, to provide automatic analyses and interpretation of medical data. The system draws much of its power by using belief network methods in place of more traditional, but difficult to automate, classical multivariate statistical techniques. Data Explorer identifies statistically significant relationships among variables, and using power-size analysis, belief network inference/learning and various explanatory techniques helps the user understand the importance of the findings. Finally the system can be used as a tool for the automatic development of predictive/diagnostic models from patient databases.

Artificial Intelligence

Vitamin B12 and folate status of a selected group of free-living older persons.

Vitamin B12 and folate status was determined in 50 male and 47 female free-living subjects (65-77 years) in winter and summer. The mean intake calculated from 3-day food records met the Canadian recommended intake (RNI) for both gender and season, however, probability analysis of dietary data revealed a number of subjects at risk of deficiency. Although the mean plasma levels were within the acceptable range for both vitamins, some 9 to 14% of individual subjects had folate plasma levels below normal. Fewer subjects had subnormal plasma vitamin B12 levels. Although mean values for dietary intake and plasma concentration of folate and vitamin B12 may indicate nutritional adequacy, a proportion of an older population may be at nutritional risk.

Aged

Measurement of vertebral area on spine x-rays in osteoporosis: reliability of digitizing techniques.

Much of the clinical research in osteoporosis is directed toward documenting a reduction in vertebral fracture rate, but there is considerable disagreement about defining and quantifying vertebral fractures. We have evaluated the technique of digitizing landmarks identified on lateral radiographs of thoracic and lumbar vertebrae and computing vertebral body area. Reduction in area indicates that fractures occurred. Radiographs from 10 patients with osteoporosis and vertebral fractures were obtained from each of two centers. Henry Ford Hospital (HFH) and Mayo Clinic (MC), and vertebral area for each individual in the complete set of 20 radiographs was calculated at each center. Measurements at the two centers differed by a multiplicative constant related to the method of recording landmarks on the radiographs that was estimated using 300 x-rays from HFH. After adjusting the MC areas for this multiplicative relationship, the average ratio of the HFH areas to the transformed MC areas of individual vertebrae (T4-L5) ranged from 0.98 to 1.06. The correlation between HFH and transformed MC areas for individual vertebrae averaged 0.85, with slopes between 0.87 and 1.00, intercept average -0.57. Within-patient rank correlation averaged 0.97. We conclude that radiographic digitization is a reliable and reproducible method of determining vertebral body dimensions that is suitable for evaluating radiographs obtained at different clinical sites and for comparison with normal data. This technique should prove useful for documenting the presence of a vertebral fracture that may not be readily apparent on visual inspection of radiographs and for monitoring serial changes in vertebral body dimensions in long-term epidemiologic and therapeutic studies.

Aged

Leukemogenicity of Moloney murine leukemia viruses carrying polyoma enhancer sequences in the long terminal repeat is dependent on the nature of the inserted polyoma sequences.

The leukomogenicity of Moloney murine leukemia virus (M-MuLV) variants with chimeric long terminal repeats (LTRs) containing sequences from polyomavirus was studied. We previously showed that insertion of the B enhancer element from the PyF101 variant into the M-MuLV LTR between the M-MuLV enhancers and promoter abolished leukemogenicity. PyF101 differs from wild-type polyoma in that it can productively infect undifferentiated F9 embryonal carcinoma cells; this is due to alterations in the B enhancer element. Two additional chimeric M-MuLVs were generated that contained the B enhancers from wild-type polyoma and also from a second host range variant (PyF441), which differs from wild-type polyoma by only a single base change. In contrast to Mo+PyF101 M-MuLV, both Mo+Pywt and Mo+-PyF441 M-MuLV induced T-lymphoid leukemia in neonatal NIH Swiss mice with the same time course as wild-type M-MuLV. Thus the lack of leukemogenicity of Mo+PyF101 M-MuLV was related to the exact nature of the PyF101 B enhancers. While both Mo+Pywt and Mo+PyF441 M-MuLVs induced leukemia, they showed differences when the resulting tumors were examined. First, approximately one-third of the tumors induced by Mo+Pywt M-MuLV contained proviruses which lacked polyoma sequences, while all of the tumors induced by Mo+PyF441 M-MuLV contained proviruses with the chimeric LTR. Second, a majority of tumors induced by Mo+Pywt M-MuLV (and also wild-type, M-MuLV) showed proviral integrations near one or more of the cellular c-myc, pim-1, or pvt-1 loci. In contrast, tumors induced by Mo+PyF441 M-MuLV showed infrequent integrations at these loci.

Animals

Prosthetic replacement of the proximal humerus.

Eighteen patients had prosthetic proximal humeral replacement with either a metal or ceramic prosthesis. Three replacements were performed for fracture nonunions, five for benign neoplasms, six for low-grade malignancies, and four for high-grade malignancies. Retention of elbow and hand function was good. In five of the 11 ceramic prostheses, failure occurred at the humeral-prosthetic junction even though it was designed for biologic fixation. Ten of 18 prostheses subluxated or dislocated. Twelve of 18 patients have had revision operations. While the revision rate in this initial series was high, valuable experience was gained for further investigations of shoulder arthroplasty.

Adolescent

Rearrangements and insertions in the Moloney murine leukemia virus long terminal repeat alter biological properties in vivo and in vitro.

The effects of rearrangement and insertion of sequences in the Moloney murine leukemia virus (M-MuLV) long terminal repeat (LTR) were investigated. The alterations were made by recombinant DNA manipulations on a plasmid subclone containing an M-MuLV LTR. Promoter activity of altered LTRs was measured by fusion to the bacterial chloramphenicol acetyltransferase gene, followed by transient expression assay in NIH 3T3 cells. M-MuLV proviral organizations containing the altered LTRs were also generated, and infectious virus was recovered by transfection. Infectivity of the resulting virus was quantified by XC plaque assay, and pathogenicity was determined by inoculating neonatal NIH Swiss mice. Inversion of sequences in the U3 region containing the tandemly repeated enhancer sequences (-150 to -353 base pairs [bp]) reduced promoter activity approximately fivefold in the transient-expression assays. Infectious virus containing the inverted sequences (Mo- M-MuLV) showed a 20-fold reduction in relative infectivity compared with wild-type M-MuLV, but the virus still induced thymus-derived lymphoblastic lymphoma or leukemia in mice, with essentially the same kinetics as for wild-type M-MuLV. We previously derived an M-MuLV which carried inserted enhancer sequences from the F101 strain of polyomavirus (Mo + PyF101 M-MuLV) and showed that this virus is nonleukemogenic. In Mo + PyF101 M-MuLV, the PyF101 sequences were inserted between the M-MuLV promoter and the M-MuLV enhancers (at -150 bp). A new LTR was generated in which the PyF101 sequences were inserted to the 5' side of the M-MuLV enhancers (at -353 bp, PyF101 + Mo M-MuLV). The PyF101 + Mo LTR exhibited promoter activity similar (40 to 50%) to that of wild-type M-MuLV, and infectious PyF101 + Mo M-MuLV had high infectivity on NIH 3T3 cells (50% of wild type). In contrast to the nonleukemogenic Mo + PyF101 M-MuLV, PyF101 + Mo M-MuLV induced leukemia with kinetics similar to that of wild-type M-MuLV. Thus, the position of the PyF101 sequences relative to the M-MuLV LTR affected the biological behavior of the molecular construct. Furthermore, PyF101 + Mo M-MuLV induced a different spectrum of neoplastic disease. In comparison with wild-type M-MuLV, which induces a characteristic thymus-derived lymphoblastic lymphoma with extremely high frequency, PyF101 + Mo M-MuLV was capable of inducing both acute myeloid leukemia or thymus-derived lymphoblastic lymphoma, or both. Tumor DNA from both the PyF101 + Mo- and Mo- M-MuLV-inoculated animals contained recombinant proviruses with LTRs that differed from the initially inoculated virus.

Animals

Characterization of murine hepatoma BW7756. III. Hematological profile of a tumor-associated anemia.

A severe anemia develops in recipient C57L/J mice after syngeneic transplantation of the BW7756 murine hepatoma. The tumor undergoes an exponential growth spurt in the 14-21 days post-implantation, accompanied by a parallel increase in serum alpha-fetoprotein levels and a significant decrease of hemoglobin concentration and hematocrit extending to the 28th day. Concomitant with the decreased hematocrit, the blood volume displayed a 10% increase. The blood cell population was generally one of reticulocytosis and leukocytosis. Mild icteric plasma was observed and both "cold" and "warm" antibodies were detected in the sera of tumor-bearing mice. An elevation of IgM was observed by day 7, followed by a depletion of IgG1 and IgG2 throughout the tumor growth period. When RBCs of tumor-bearing mice were compared to those of normal mice, the same degree of osmotic fragility was found. However, the lifespan of the transfused RBC was shorter in tumor-bearing mice than in normal mice (half-life: 2 days vs. 4 days). The data suggest a type of auto-immune hemolytic anemia which is analogous to various hematopoietic disturbances described for murine hosts bearing solid tumors distal to hematopoietic sites.

Anemia, Hemolytic

Construction and characterization of Moloney murine leukemia virus mutants unable to synthesize glycosylated gag polyprotein.

Murine leukemia virus (MuLV) encodes two independent pathways for expression of the gag gene. One pathway results in processing and cleavage of the precursor Pr65gag to yield the internal capsid proteins of the virion and is analogous to gag polyprotein precursors for all classes of retroviruses. The other pathway, which is not encoded by several other classes of retroviruses, begins with a glycosylated polyprotein gPr80gag . gPr80gag is synthesized independently of Pr65gag; it contains Pr65gag peptides and additional amino-terminal protein. It is modified by further addition of carbohydrate, exported to the cell surface, and released from the cell but does not appear in virus particles. To investigate the role of glycosylated gag in MuLV infection, two mutants of Moloney MuLV (M-MuLV) deficient for synthesis of gPr80gag but able to synthesize Pr65gag were constructed. The mutants were obtained by substitution into a molecular clone of M-MuLV DNA by DNA from two acutely transforming viruses, Ableson MuLV (Ab-MuLV) and Moloney murine sarcoma virus (M-MSV). Both Ab-MuLV and M-MSV are derived from M-MuLV and they express M-MuLV gag sequences, but some strains do not synthesize glycosylated gag protein. For Ab-MuLV, a 177-base-pair Pst I fragment from the P90 strain containing the initiation codon for Pr65gag was substituted for the equivalent fragment in M-MuLV DNA. For M-MSV, 1.5 kilobases at the 5' end of the genome was substituted. Transfection of the recombined DNAs onto NIH-3T3 cells produced infectious M-MuLV, although the infected cells did not produce gPr80gag. Therefore glycosylated gag is not absolutely required for MuLV replication. Deletion of the glycosylated gag pathway did not significantly reduce the level of virus production, although a minor difference in XC plaque morphology was observed.

Animals

Segmental replacement of long bones using titanium fiber metal composite following tumor resection.

A series of 17 long bone defects following tumor resections were reconstructed using titanium fiber metal implants with adequate bone grafts. There were nine diaphyseal segmental arthroplasties and eight arthrodeses of the knee. The results were excellent in 11 and satisfactory in five, and there was one failure. Sixteen patients became fully weight-bearing. Adequate bone grafts, especially from both posterior iliac crests, and good skin coverage are essential to adequate bony reconstruction.

Adult

Simple modification of the cellulose acetate method for identifying adult hemoglobin (hemoglobin A) in dried specimens of newborn blood.

Definition of hemoglobin A in cellulose acetate electrophoretograms of eluate from air-dried specimens of newborns' blood was improved by adding glycerine to the Tris--ethylenediametetraacetic acid--borate buffer system. Examination of 1,672 randomly received samples showed no reduction in ability to detect hemoglobin S with the modified buffer. The method may be adopted as a useful adjunct to current technics for rapid electrophoretic screening of neonatal dried blood samples.

Blood Protein Electrophoresis

Non-function of a Moloney murine leukaemia virus regulatory sequence in F9 embryonal carcinoma cells.

Moloney murine leukaemia virus (M-MuLV) infection of embryonal carcinoma (EC) cells results in the integration of proviral DNA into the host cell genome, but not in virus production. One suggested explanation for the lack of viral gene expression in EC cells has been methylation of the integrated viral DNA. However, subsequent reports indicated that integration of the M-MuLV DNA occurs soon after infection, but that viral DNA methylation occurs considerably later. Nevertheless, viral gene expression is not observed even at early times. One possible explanation is that certain M-MuLV regulatory sequences do not function in EC cells. We now present evidence which supports this hypothesis.

Acetyltransferases