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Electrophoretic mobility profiles of mouse leukemias: I. Electrophoresis of normal mouse thymus and lymph node cell populations.

Anodic electrophoretic mobility of thymocytes and lymph node cells from random-bred ICR Swiss mice was examined. Three cell populations were identified which differed in their surface charge as reflected in their distinct mean AEM and in their time of appearance during the course of life. The first electrophoretically slow-moving population with a mean AEM of 0.97 microns sec-1 V-1 cm was detected in the early postnatal period. In the first month after birth, the first population was replaced by a second, slower-moving population with a mean AEM of 0.83 microns sec-1 V-1 cm. In the second month after birth, a third, fast-moving population with a mean AEM value of 1.24 microns sec-1 V-1 cm appeared in addition to the second cell population. The third population constituted only a minority of thymus cells and continued to be present, as well as the second cell population, up to two years of age. Lymph node cells of ICR mice showed a typical bimodal electrophoretic distribution; fast LNC displayed a mean AEM of 1.18 microns sec-1 V-1 cm whereas slow LNC that of 0.76 microns sec-1 V-1 cm. The percentage of cells in the fast- and slow-moving LNC subpopulations was similar to the expected percentage of T and B LNC. Fractionation of the ICR LNC on nylon wool columns revealed that the majority of the fast-moving LNC corresponded to the nonadherent Thy 1.2+ lymphocytes and the majority of the slow-moving LNC to the nylon wool-adherent sIg+ lymphocytes.

Animals↗

Modulation of fat-soluble vitamin concentrations and blood mononuclear leukocyte populations in milk replacer-fed calves by dietary vitamin A and beta-carotene.

Dairy calves (n = 18), separated from dams at birth, were fed 1 L of pooled-colostrum. For the remaining 7 wk of the study, they were fed one of three diets consisting of either a custom-formulated milk replacer without vitamin A (controls), or supplemented with retinyl palmitate (equivalent to 32,000 IU of vitamin A/d) or with beta-carotene (equivalent to 20,000 IU of vitamin A/d). Plasma retinol, beta-carotene, and RRR-alpha-tocopherol concentrations were lowest at birth, and increased substantially from birth to 1 wk postpartum in all groups, a probable consequence of ingestion of colostrum. From 1 to 7 wk of age, retinol concentrations were greatest in retinyl palmitate-supplemented calves, intermediate in beta-carotene-supplemented calves and lowest in control calves. At 2, 3, 5, 6, and 7 wk, RRR-alpha-tocopherol concentrations were lower in retinyl palmitate-supplemented calves than in control calves. A negative correlation between plasma retinol and vitamin E concentrations existed from wk 2 to 7, suggesting vitamin A influences the absorption and distribution of RRR-alpha-tocopherol. Supplemental retinyl palmitate, but not beta-carotene, was associated with a reduction in the percentage of blood mononuclear leukocytes expressing CD2, CD4, and CD8-T cell antigens and interleukin-2 receptors. By wk 7, leukocyte populations from retinyl palmitate-supplemented calves were more similar to those from adult cattle than those from control calves, suggesting that supplemental vitamin A, as retinyl palmitate, affects the maturation of the neonatal immune system. Differences in the composition of blood mononuclear leukocyte populations may represent changes in immune competency.

Animals↗

A comparison of self-reported hip symptomatology in hip replacement patients and a population-based sample of medicare beneficiaries.

BACKGROUND: There exists variation over geographic areas in the use of total hip arthroplasty. This variation is not explained by the variation in the density per unit area of surgeons. The objective was to compare the severity of hip symptoms between a population-based sample of community-dwelling Medicare beneficiaries and a hospital-based sample of patients undergoing total hip replacement surgery. MATERIAL/METHODS: Population-based survey data on 113 community residents were compared to data from an independent sample of 157 hospital-based patients who underwent total hip replacement surgery, all of whom were 65 years and older. Severity of symptoms in both groups was rated using the Hip Rating Questionnaire (HRQ). RESULTS: The average population sample HRQ score was 63+/-9.0; overall arthritis impact 12+/-5, pain 14+/-6, walking 18+/-4, function 19+/-4. The average patient sample HRQ score was 56+/-14; overall arthritis impact 10+/-7, pain 11+/-4, walking 15+/-4, function 20+/-3. CONCLUSIONS: Community-dwelling individuals report symptoms as severe as patients who have undergone total hip arthroplasty. Further research is necessary to identify the reasons for the low incidence of treatment for those living in the community.

Activities of Daily Living↗

Wide tissue distribution of axolotl class II molecules occurs independently of thyroxin.

Unlike most salamanders, the Mexican axolotl (Ambystoma mexicanum) fails to produce enough thyroxin to undergo anatomical metamorphosis, although a "cryptic metamorphosis" involving a change from fetal to adult hemoglobins has been described. To understand to what extent the development of the axolotl hemopoietic system is linked to anatomical metamorphosis, we examined the appearance and thyroxin dependence of class II molecules on thymus, blood, and spleen cells, using both flow cytometry and biosynthetic labeling followed by immunoprecipitation. Class II molecules are present on B cells as early as 7 weeks after hatching, the first time analyzed. At this time, most thymocytes, all T cells, and all erythrocytes lack class II molecules, but first thymocytes at 17 weeks, then T cells at 22 weeks, and finally erythrocytes at 26-27 weeks virtually all bear class II molecules. Class II molecules and adult hemoglobin appear at roughly the same time in erythrocytes. These data are most easily explained by populations of class II-negative cells being replaced by populations of class II-positive cells, and they show that the hemopoietic system matures at a variety of times unrelated to the increase of thyroxin that drives anatomical metamorphosis. We found that administration of thyroxin during axolotl ontogeny does not accelerate or otherwise affect the acquisition of class II molecules, nor does administration of drugs that inhibit thyroxin (sodium perchlorate, thiourea, methimazole, and 1-methyl imidazole) retard or abolish this acquisition, suggesting that the programs for anatomical metamorphosis and some aspects of hemopoietic development are entirely separate.

Ambystoma↗

Molecular genetics of speciation and human origins.

The major histocompatibility complex (MHC) plays a cardinal role in the defense of vertebrates against parasites and other pathogens. In some genes there are extensive and ancient polymorphisms that have passed from ancestral to descendant species and are shared among contemporary species. The polymorphism at the DRB1 locus, represented by 58 known alleles in humans, has existed for at least 30 million years and is shared by humans, apes, and other primates. The coalescence theory of populations genetics leads to the conclusion that the DRB1 polymorphism requires that the population ancestral to modern humans has maintained a mean effective size of 100,000 individuals over the 30-million-year persistence of this polymorphism. We explore the possibility of occasional population bottlenecks and conclude that the ancestral population could not have at any time consisted of fewer than several thousand individuals. The MHC polymorphisms exclude the theory claiming, on the basis of mitochondrial DNA polymorphisms, that a constriction down to one or few women occurred in Africa, at the transition from archaic to anatomically modern humans, some 200,000 years ago. The data are consistent with, but do not provide specific support for, the claim that human populations throughout the World were at that time replaced by populations migrating from Africa. The MHC and other molecular polymorphisms are consistent with a "multiregional" theory of Pleistocene human evolution that proposes regional continuity of human populations since the time of migrations of Homo erectus to the present, with distinctive regional selective pressures and occasional migrations between populations.

Animals↗

BD ProbeTec ET assay for the diagnosis of gonorrhoea in a high-risk population: a protocol for replacing traditional microscopy and culture techniques.

OBJECTIVES: To evaluate the Neisseria gonorrhoeae Becton Dickinson (BD) ProbeTec strand displacement assay (SDA) on female endocervical swab and male first void urine against culture for Neisseria gonorrhoeae on female endocervical and urethral swab for the diagnosis of N gonorrhoeae infection in genitourinary medicine (GUM) attendees. To determine an algorithm for implementation of N gonorrhoeae infection screening by SDA in these patients taking account of the desirability of having a N gonorrhoeae isolate in people with N gonorrhoeae infection. METHODS: Initially, 1582 patients attending the GUM clinic were tested for N gonorrhoeae infection by SDA and routine microscopy, and culture. On the basis of the results, a protocol for diagnosis of N gonorrhoeae infection by SDA, with culture specimens only from patients with a listed risk factor for acquiring N gonorrhoeae infection, was devised and implemented. A post implementation audit was done to assess the effectiveness of this protocol for routine service use. RESULTS: There was good concurrence between the N gonorrhoeae SDA and culture results with a N gonorrhoeae infection prevalence rate of 3.4% by both methods. All men and 85% of women with N gonorrhoeae infection had an identifiable risk factor for acquiring infection. Overall, 38% men and 60% women attending the GUM clinic had this listed risk factor for acquiring N gonorrhoeae. Post implementation audit confirmed the initial findings. CONCLUSION: Nucleic acid amplification techniques like the SDA are sensitive and specific for diagnosis of N gonorrhoeae. We were able to list certain risk factors, which were predictive of those patients most likely to have N gonorrhoeae infection. To obtain timely sensitivity data, a culture specimen should also be submitted at the same time from patients deemed to have a listed risk factor for acquiring Neisseria gonorrhoeae infection.

Bacteriological Techniques↗

Immigration, below-replacement fertility, and long-term national population trends.

The long-term demographic effects of immigration on a population experiencing below-replacement fertility are studied by assuming that the size and age composition of the immigrant population do not change over time. The size of the first-generation immigrant population becomes stationary within a time period not greater than the human life span. Thereafter, the number dying equals the number entering over any given time interval. The stationarity of the native population, among which deaths exceed births, is maintained by the compensating number of births to the immigrant population. The limiting age distribution of the country's population, although stationary, may not decline monotonically with age and may look like a camel's back, with one or two humps.

Demography↗

In vivo separation of two classes of T cells as determined by negative selection after the injection of UV-treated allogeneic lymphoid cells.

Negative selection occurred when gamma-irradiated lymphoid cells of rat strain PVG were injected intravenously into strain Fischer rats, which differ from PVG rats at the major histocompatibility complex. By 48 hr after injection, thoracic duct lymphocytes (TDL) from these animals failed to proliferate or generate cytotoxic T lymphocytes (CTL) in vitro in response to gamma-irradiated PVG lymphoid cells. Responses to cells of a third rat strain were unaffected. By about 6 days after antigen injection, positive selection had occurred, as shown by enhanced responses to gamma-irradiated PVG cells in the same assays. Ultraviolet-irradiated strain PVG populations were tested in the same way. They differed from gamma-irradiated PVG cells in that they failed to induce proliferation or stimulate CTL in vitro. TDL from Fischer rats injected with UV-irradiated PVG cells failed to proliferate or generate CTL in response to gamma-irradiated PVG cells in vitro. The CTL response of TDL from rats injected with UV-irradiated cells was restored by the addition of supernatant factor(s) from concanavalin A-stimulated lymphoid cells (ConA SnF). Therefore, CTL precursors did not undergo negative selection after injection of UV-treated cells. There was also no detectable positive selection 6 days after injection of UV-treated cells. These experiments show that it is possible to separate two populations of T cells in vivo by the injection of UV-irradiated allogeneic lymphoid cells. One population incorporates [3H]thymidine early in an allogeneic response in vitro, the other expresses cytotoxic activity only after the addition of ConA SnF in vitro. The first population can replace the requirement for ConA SnF by the CTL population.

Animals↗

Cancer risk after hip replacement with metal implants: a population-based cohort study in Sweden.

BACKGROUND: Joint replacement with metal implants has been the standard procedure for surgical treatment of irreversible degeneration of hip and knee joints for more than two decades. However, reports of local malignancy after joint replacement and experimental studies that suggest a carcinogenic action of metal ions and polymethylmethacrylate (an acrylic compound used to stabilize the implant in the host) have raised concern about the possible long-term risks associated with metal implants. PURPOSE: Our aim was to study cancer risk in a Swedish cohort of patients who had hip replacement surgery during the period 1965 through 1983. METHODS: We studied the risk of cancer in a cohort of 39 154 patients (14 869 men and 24 285 women), identified in the nationwide Swedish Inpatient Register with at least one hip replacement during the period 1965 through 1983. The patients were followed through 1989 by means of record linkage to the Swedish Cancer Register. The cohort contributed a total of 327 922 person-years at risk. Standardized incidence ratios (SIRs) were computed using age-, sex-, and period-specific incidence rates derived from the entire Swedish population. RESULTS: The overall relative risk of cancer was increased by only 3%. Bone cancer--the focus of previous concerns--occurred in six cases versus 4.3 expected, and connective tissue cancer occurred in 28 cases versus 25.9 expected. Increased risks were observed for kidney cancer (SIR = 1.31; 95% confidence interval [CI] = 1.13-1.51), prostate cancer (SIR = 1.13; 95% CI = 1.04-1.22), and melanoma (SIR = 1.23; 95% CI = 1.00-1.50). The relative risk of gastric cancer steadily declined with increasing follow-up time, in both men and women (SIR = 0.58; 95% CI = 0.39-0.84 more than 10 years after hip replacement). CONCLUSION: In this study, the largest study to date to evaluate hip replacement and subsequent cancer risk, the overall cancer risk appears to be negligible from a public health perspective, and our results have not produced any strong evidence against the continued use of these devices. Nevertheless, the small but statistically significant increases in kidney and prostate cancers and the decrease in gastric cancer deserve further study.

Aged↗

Population requirement for primary hip-replacement surgery: a cross-sectional study.

BACKGROUND: There has been a long-standing failure in many countries to satisfy the demand for several elective surgical treatments, including total hip replacement. We set out to estimate the population requirement for primary total hip replacement in England. METHODS: We undertook a cross-sectional study of a stratified random sample of 28,080 individuals aged 35 and over from 40 general practices in inner-city, urban, and rural areas of Avon and Somerset, UK. Prevalent disease was identified through a two-stage process: a self-report screening questionnaire (22,978 of 26,046 responded) and subsequent clinical examination. Incident disease was estimated from the point prevalence by statistical modelling. The requirement for total hip replacement surgery was estimated on the basis of pain and loss of functional ability, with adjustment for evidence of comorbidity and patients' treatment preferences. FINDINGS: 3169 people reported hip pain on the screening questionnaire. 2018 were invited for clinical examination, and 1405 attended. The prevalence of self-reported hip pain was 107 per 1000 (95% CI 101-113) for men and 173 per 1000 (166-180) for women. The prevalence of hip disease severe enough to require surgery was 15.2 (12.7-17.8) per 1000 aged 35-85 years. The corresponding annual incidence of hip disease requiring surgery was estimated as 2.23 (1.56-2.90), which suggests an overall requirement in England of 46,600 operations per year for patients who expressed a preference for, and were suitable for, surgery; the recent actual provision in England was about 43,500. INTERPRETATION: This research suggests that the satisfaction of demand for total hip replacement, given agreed criteria for surgery, is a realistic objective.

Adult↗

[Hormone replacement therapy and cardiovascular diseases: different populations, different risks].

Observational studies indicate that oral hormone replacement therapy (HRT) in menopause is associated with a 20-40% reduction of coronary risk. Population risk/benefit analyses on mortality after large-scale HRT use indicate that excess deaths can be counted when coronary heart disease is relatively less frequent than breast cancer before age 60 (as occurs in Italy). The decline in mortality trends for coronary heart disease support a word for caution for a large scale use of HRT in the next years even in those populations for which a relative advantage is presently estimated.

Cardiovascular Diseases↗

Rates and outcomes of primary and revision total hip replacement in the United States medicare population.

BACKGROUND: Information on the epidemiology of primary total hip replacement is limited, and we are not aware of any reports on the epidemiology of revision total hip replacement. The objective of this study was to characterize the rates and immediate postoperative outcomes of primary and revision total hip replacement in persons sixty-five years of age and older residing in the United States. METHODS: We used Medicare claims submitted by hospitals, physicians, and outpatient facilities between July 1, 1995, and June 30, 1996, to identify individuals who had undergone elective primary total hip replacement for a reason other than a fracture (61,568 patients) or had had revision total hip replacement (13,483 patients). Annual incidence rates of primary and revision total hip replacement were calculated, and multivariate modeling was used to evaluate the association between patient characteristics and surgical rates. The rates of occurrence of five complications within ninety days postoperatively were also evaluated, and relationships between those outcomes and patient characteristics were assessed with use of multivariate models adjusted for hospital and surgeon volume. RESULTS: The rates of primary total hip replacement were three to six times higher than the rates of revision total hip replacement. Women had higher rates than men, and whites had higher rates than blacks. The rates of primary and revision total hip replacement increased with age until the age of seventy-five to seventy-nine years and then declined. The rates of complications occurring within ninety days after primary total hip replacement were 1.0% for mortality, 0.9% for pulmonary embolus, 0.2% for wound infection, 4.6% for hospital readmission, and 3.1% for hip dislocation. The rates after revision total hip replacement were 2.6%, 0.8%, 0.95%, 10.0%, and 8.4%, respectively. Factors associated with an increased risk of an adverse outcome included increased age, gender (men were at higher risk than women), race (blacks were at higher risk than whites), a medical comorbidity, and a low income. CONCLUSIONS: Analysis of United States Medicare population data showed that the rates of total hip replacement increased with age up to the age of seventy-five to seventy-nine years and that blacks had a significantly lower rate of total hip replacement than whites. The overall rates of adverse outcomes were relatively low, but they were significantly higher after revision than after primary total hip replacement. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See p. 2 for complete description of levels of evidence.

Age Factors↗

The ecology of antigenic variation.

A detailed molecular analysis using recombinant DNA technologies is extremely important to our understanding of the phenomena of antigenic variation in the African trypanosomes; however, by itself, it may not completely explain antigenic variation as it occurs in vivo. Several laboratories have demonstrated the ability of one variant population to replace another in vivo as well as the presence of heterogeneous populations of trypanosomes within an individual animal. These two phenomena do not permit us to explain antigen variation solely on the basis of the molecular regulation of variant antigen expression. In addition to studies in molecular biology, it will be necessary to define clearly the differences in growth rates of variant populations and the role of competition between these variants in a single anatomical site. It will also be necessary to determine the influence of various physiological environments on growth rates and the competition between the different variants of a single repertoire. It is concluded that the phenomenon of antigenic variation is a complex problem in ecology and population dynamics as well as molecular regulation. This paper is designated to examine a variety of the ecological parameters presumably involved in antigenic variation.

Animals↗