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Biomedical subjects

C Cooper

Publications and source records attributed to C Cooper.

At least 19 recordsLinked to original sources

The C/EBP family of transcriptional activators is functionally important for Ig VH promoter activity in vivo and in vitro.

We have examined the functional importance of binding sites for C/EBP family members (E sites), in two Ig VH promoters: VH1, a member of the S107 family, and BCL1, a member of the J558 family. Mutation of the E site in the VH1 promoter diminishes transcription in vivo to 59% of wild-type and transcription from the BCL1 promoter in vitro is inhibited to an average of 39% of wild-type by competition with E site oligonucleotides. Purified E site binding proteins from plasmacytoma cells stimulated BCL1 transcription in vitro 2.3-fold. Although five C/EBP family proteins are known which bind the E site, antibody ablation of DNA:protein complexes resolved by electrophoretic mobility shift assays showed that Ig/EBP-1 is the only E site binding protein detectable in early B cell lines; more mature B cells contain Ig/EBP-1 and NF-IL6. We also show by antibody-depletion that Ig/EBP-1 activates the BCL1 promoter in vitro.

Animals

Osteoarthritis of the hip: an occupational disease in farmers.

OBJECTIVE: To test the hypothesis that farmers are at high risk of hip osteoarthritis and to investigate possible causes for such a hazard. DESIGN: Cross sectional survey. SETTING: Five rural general practices. SUBJECTS: 167 male farmers aged 60-76 and 83 controls from mainly sedentary jobs. All those without previous hip replacement underwent radiography of the hip. MAIN OUTCOME MEASURES: Hip replacement for osteoarthritis or radiological evidence of hip osteoarthritis. RESULTS: Prevalence of hip osteoarthritis was higher in farmers than controls and especially in those who had farmed for over 10 years (odds ratio 9.3, 95% confidence interval 1.9 to 44.5). The excess could not be attributed to any one type of farming, and heavy lifting seems the likely explanation. CONCLUSIONS: Manual handling in agriculture should be limited where possible. Consideration should be given to making hip osteoarthritis a prescribed industrial disease in farmers. There may be wider implications for the prevention of hip osteoarthritis in the general population.

Age Factors

Ankylosing spondylitis in Rochester, Minnesota, 1935-1989. Is the epidemiology changing?

OBJECTIVE: To determine trends in the incidence and clinical presentation of ankylosing spondylitis first diagnosed between 1935 and 1989 among residents of Rochester, Minnesota, and in the survival of the patients. METHODS: Population-based descriptive study. RESULTS: The overall age- and sex-adjusted incidence rate was 7.3 per 100,000 person-years (95% confidence interval 6.1-8.4). The rate tended to decline between 1935 and 1989, but there was little change in the age at symptom onset or diagnosis over the 55-year study period. Overall survival was not decreased up to 28 years following diagnosis. CONCLUSION: These data indicate that there is a constancy in the epidemiologic characteristics of ankylosing spondylitis and suggest that previously study results indicating changes may have been due to biases in patient selection and study design.

Adolescent

Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989.

Vertebral fractures are the classic hallmark of osteoporosis, yet little is known of their epidemiology. The incidence of clinically diagnosed vertebral fractures was therefore directly assessed in the predominantly white (European descent) population of Rochester, Minnesota. Altogether, 341 Rochester residents were radiologically diagnosed for the first time with one or more vertebral fractures in the 5 year study period, 1985-1989. The overall age- and sex-adjusted incidence rate was 117 per 100,000 person-years (95% CI, 105 to 130). The age-adjusted rate in women (145 per 100,000 person-years) was almost twice that in men (73 per 100,000 person-years). Of all fractures, 47 (14%) followed severe trauma, 282 (83%) followed moderate or no trauma, and 12 (3%) were pathologic. Incidence rates for fractures following moderate trauma were higher in women than in men and rose steeply with age in both genders. In contrast, fractures following severe trauma were more frequent in men, and their incidence increased less with age. These Rochester rates are greater than those previously reported from studies in Britain and Sweden but lower than the incidence rates extrapolated from a prevalence study in this population.

Adult

Is caffeine consumption a risk factor for osteoporosis?

High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota. After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites. In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages. When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral. Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption. After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables. These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis. Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur.

Adult

Perspective. How many women have osteoporosis?

Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population-based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health problem.

Adult

Secular trends in the incidence of postmenopausal vertebral fractures.

Several studies suggest secular increases in hip fracture incidence through this century, but little is known about such trends for vertebral fracture. We have examined changes in the incidence of clinically ascertained vertebral fractures among Rochester, Minnesota residents aged 35-69 years, that were first diagnosed between 1950 and 1989. Our results indicate no overall increase in incidence over the 40-year period. Categorization of fractures according to the level of preceding trauma, however, revealed a significant increase in the incidence of fractures following moderate trauma among women aged 60-69 years. This increase occurred between 1950 and 1964, and leveled off thereafter. Rates for severe trauma fractures among postmenopausal women, and for vertebral fractures from any cause among younger men and women, remained stable. The rise in moderate trauma fractures in postmenopausal women paralleled that for hip fractures in Rochester and began to plateau at around the same time. It might have resulted from increased diagnosis of vertebral fractures, but the increase in hip fracture incidence is inconsistent with this explanation. An increase in the prevalence of osteoporosis, however, might account for the trend in both types of fractures.

Adult

Hip fractures in the elderly: a world-wide projection.

Hip fractures are recognized to be a major public health problem in many Western nations, most notably those in North America, Europe and Oceania. Incidence rates for hip fracture in other parts of the world are generally lower than those reported for these predominantly Caucasian populations, and this has led to the belief that osteoporosis represents less of a problem to the nations of Asia, South American and Africa. Demographic changes in the next 60 years, however, will lead to huge increases in the elderly populations of those countries. We have applied available incidence rates for hip fracture from various parts of the world to projected populations in 1990, 2025 and 2050 in order to estimate the numbers of hip fractures which might occur in each of the major continental regions. The projections indicate that the number of hip fractures occurring in the world each year will rise from 1.66 million in 1990 to 6.26 million by 2050. While Europe and North America account for about half of all hip fractures among elderly people today, this proportion will fall to around one quarter in 2050, by which time steep increases will be observed throughout Asia and Latin America. The results suggest that osteoporosis will truly become a global problem over the next half century, and that preventive strategies will be required in parts of the world where they are not currently felt to be necessary.

Adult

The association between water fluoridation and hip fracture among white women and men aged 65 years and older. A national ecologic study.

For the past 45 years, there has been a great deal of debate regarding the health issues surrounding the fluoridation of public water supplies. In order to assess the association between fluoridation and hip fracture, we identified 129 counties across the United States considered to be exposed to public water fluoridation and 194 counties without exposure. Data from the Health Care Financing Administration and the Department of Veterans Affairs were used to calculate the incidence of hip fracture among white persons, aged 65 years or older, in fluoridated and nonfluoridated counties. There was a small statistically significant positive association between fracture rates and fluoridation. The relative risk (95% confidence interval) of fracture in fluoridated counties compared to nonfluoridated counties was 1.08 (1.06 to 1.10) for women and 1.17 (1.13 to 1.22) for men. As comparisons were made at the grouped level, it may be inappropriate at this time to draw inferences at the individual level. The relationship observed at the county level needs to be duplicated at the individual level with more precise measures of fluoride exposure.

Aged

Knee pain and disability in the community.

In order to investigate the strength of any relationship between knee pain and disability, a postal questionnaire was sent to 2102 men and women aged over 55 registered at a general practice in Bristol. A response rate of 80.6% was achieved at second reminder. Knee pain was common particularly in women (27.6% overall). Disability was also more frequently reported in women (P less than 0.05) and rose with increasing age. Respondents with knee pain had significantly more disability relating to upper as well as lower limb activities (P less than 0.05).

Aged

Is the hip involved in generalized osteoarthritis?

The authors examined the association of hip osteoarthritis with the presence of Heberden's nodes in a case-control study. Subjects were men aged 60-75 years who had undergone intravenous urography as out-patients. An examination of the hands was carried out in 240 patients who had a hip replacement for osteoarthritis or a joint space less than or equal to 2.5 mm, and in 290 controls whose joint space was greater than or equal to 3.5 mm in both hips. The presence of Heberden's nodes was associated with an increased risk of radiological hip osteoarthritis, the relationship being stronger in the 51 cases with severe joint-space narrowing (odds ratio = 3.4, 95% confidence interval 1.3-9.1). There was no evidence that this association differed according to the site of joint space narrowing within the hip. The finding provides further evidence that osteoarthritis of the hip can occur as part of a generalized process and does not only result from local damage to the joints.

Aged

Hospitalization with vertebral fracture among the aged: a national population-based study, 1986-1989.

Whereas fractures related to osteoporosis have become a pressing public health concern, relatively few epidemiologic studies have focused on vertebral fractures. To shed further light on the occurrence of this injury, we collected data from the Health Care Financing Administration on 151,986 discharges listing a diagnosis of vertebral fracture over a 4-year period. After adjusting for age, white women experienced the highest rates of discharge, at 17.1 per 10,000 per year, followed by white men (9.9 per 10,000), black women (3.7 per 10,000), and black men (2.5 per 10,000). Among white women, discharge rates rose exponentially from 5.3 discharges per 10,000 population at age 65 to nearly 47.8 per 10,000 at age 90. White men, black women, and black men experienced less dramatic age-related increases in discharge rates. The similarity of these patterns to discharge rates for hip fracture suggests that the race-sex differences in vertebral fracture discharge rates may be due to differences in the incidence of vertebral fracture.

Aged

Sonography in blunt abdominal trauma: a preliminary progress report.

Evaluation of blunt abdominal trauma is clinically challenging. Diagnostic peritoneal lavage (DPL) and computed tomographic (CT) scanning have become primary diagnostic modalities. We examined the efficacy and role of ultrasonographic (US) studies in the initial abdominal evaluation of blunt trauma patients. Over an 8-month period, patients whose abdominal work-up indicated the need for DPL or CT were evaluated sonographically within the first hour after admission by trauma fellows (PGY-6) with at least 1 hour of theoretical training and 1 hour of practical training. Sonograms considered positive were those showing free peritoneal fluid or organ disruption. Hard copies of the sonograms were evaluated by a staff radiologist without knowledge of the fellows' interpretations or of DPL or CT results. Based on the fellows' interpretation of the real-time sonograms, among the first 163 patients studied were 11 true-positive, 146 true-negative, one false-positive, and five false-negative results. Sixteen patients had intra-abdominal injury documented by DPL, CT, or laparotomy. Ultrasonography was 91% sensitive in detecting the presence of hemoperitoneum. Overall, ultrasonography was 69% sensitive, 99% specific, and 96% accurate in diagnosing abdominal injury. We conclude that emergency sonography on admission can serve as a valuable adjunct to the physical diagnosis of clinically significant hemoperitoneum. It is noninvasive, portable, and accurate in determining the need for further diagnostic/surgical intervention.

Abdominal Injuries

mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization.

Southwestern (DNA-protein) screening of a murine L-cell cDNA library by using a probe for the microE3 site in the immunoglobulin heavy-chain enhancer yielded a clone, mTFE3, which is a member of the subset of basic helix-loop-helix (BHLH) proteins that also contain a leucine zipper (ZIP). Since the individual contribution of these domains is not well understood for proteins which contain them both, mutational analyses were performed to assess the functional roles of the HLH and ZIP regions for DNA binding and multimerization. The HLH region is stringently required for DNA binding but not for multimerization. The ZIP region is not stringently required for binding or multimerization, but stabilizes both multimer formation and DNA binding. A high degree of conservation at both the amino acid and nucleotide levels between the human transcription factor TFE3 and mTFE3 suggests that mTFE3 is the murine homolog of human TFE3. By using fluorescent in situ hybridization, mTFE3 was mapped to mouse chromosome X in band A2, which is just below the centromere. We show that in addition to the immunoglobulin heavy-chain microE3 site, mTFE3 binds to transcriptional elements important for lymphoid-specific, muscle-specific, and ubiquitously expressed genes. Binding of mTFE3 to DNA induces DNA bending.

Amino Acid Sequence