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Biomedical subjects

S C Miller

Publications and source records attributed to S C Miller.

At least 55 records · Page 3Linked to original sources

Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated.

A growing body of anecdotal evidence in young and adult humans suggests that certain phytochemicals have the capacity to ameliorate tumors and reduce infections, especially those mediated by virus, in vivo. These indications prompted us, therefore, to investigate the potentially immuno-stimulating effect of one such phytocompound, Echinacea purpurea, on natural killer (NK) cells since these cells are active in spontaneous, non-specific immunity against neoplasms and virus-mediated infections. We elected to study aging mice, since, at this stage of life, like humans, the above-mentioned afflictions increase in frequency. We had previously found that neither the cytokine, interleukin-2, nor the pharmacological agent, indomethacin, both potent stimulators of NK cell numbers/function in younger adult mice, was effective in stimulating NK cells in elderly mice. The present study was designed to assess the numbers/production of NK cells in the spleen and bone marrow of aging, normal mice, after in vivo dietary administration of E. purpurea (14 days), or, after injection of thyroxin, a stimulant of NK cell function (10 days). Immunoperoxidase labeling techniques, coupled with hematologic tetrachrome staining were used to identify NK cells in both the spleen (primary site of NK cell function) and the bone marrow (site of NK cell generation). Double immunofluorscence staining, employing propidium iodide, was used to assess NK cell lytic function. Our results revealed that E. purpurea, but not thyroxin, had the capacity to increase NK cell numbers, in aging mice, reflecting increased new NK cell production in their bone marrow generation site, leading to an increase in the absolute numbers of NK cells in the spleen, their primary destiny. The E. purpurea-mediated increase in NK cell numbers was indeed paralleled by an increase in their anti-tumor, lytic functional capacity. Collectively, the data indicate that E. purpurea, at least, and possibly other plant compounds, appear to contain phytochemicals capable of stimulating de novo production of NK cells, as well as augmenting their cytolytic function, in animals of advanced age.

Aging↗

Melatonin inhibits apoptosis during early B-cell development in mouse bone marrow.

The pineal secretory product, melatonin, exerts a variety of effects on the immune system. Administration of melatonin stimulates cell-mediated immunity, particularly by inhibiting apoptosis among T lymphocytes in the thymus and inducing production of T-cell-derived cytokines. However, its possible effects on the humoral immune system are unclear. In the present study, we have examined whether melatonin may influence the in vivo development of B lymphocytes in mouse bone marrow, a process in which apoptosis is normally a prominent feature. Double immunofluorescence labeling and flow cytometry were used to quantitate phenotypically defined precursor B-cell and mature B-cell populations and their apoptotic rates in bone marrow of mice fed either melatonin-containing or control diet for 16 days from 9 wk of age. In short-term bone marrow cultures, the incidence of apoptosis among large pre-B cells, including cells expressing the lambda5 component of pre-B-cell receptor, was markedly reduced in melatonin-treated mice, associated with an increase in the absolute number of large pre-B cells in bone marrow. In contrast, apoptosis of earlier precursor B cells and mature B lymphocytes did not differ from control values. The results indicate that orally administered melatonin can substantially promote the survival of precursor B cells in mouse bone marrow. Melatonin treatment may thus boost the survival of newly formed B cells mediating humoral immunity.

Animals↗

Reproductive longevity and increased life expectancy.

BACKGROUND: Female life expectancy in developed countries has increased by 30 years in the twentieth century. AIM: To determine if there has been an increase in reproductive longevity. METHODS: We analysed age-specific fertility data from birth statistics for the USA, Canada, Japan, France, Sweden, the UK and Australia. RESULTS: Since 1940, birth rates for women aged 35 and over have declined. Among women aged 50 years and older, there has been no increase in births. Fertility rates in 1990 were 0.0 to 0.044 per 1000 women, with total numbers ranging from 0 to 60 births. CONCLUSION: The fertile years have not been prolonged in the cohort of women whose life expectancy has increased so dramatically this century. This suggests that reproductive senescence is tightly controlled and not extended by factors that enhance female longevity. Other physiological mechanisms may also be fixed within narrow age limits.

Adult↗

Biokinetic and dosimetric model of plutonium in the dog.

A biokinetic model of the systemic distribution and dosimetry of 239Pu in the beagle dog is presented. To achieve maximum consistency with experimental data, known histomorphometric parameters and results of autoradiographic studies were adopted directly. The remaining parameters were determined from retention and excretion measurements by optimization procedures. The beagle model attempts to parallel the human model as much as possible, but only one liver compartment and one compartment representing other soft tissues were needed to describe the data adequately. The salient features and differences of the biokinetic behavior of 239Pu beagles and humans are compared. Generally the organ retention of the beagle in relation to the lifetime is longer than in humans. This is particularly pronounced in the skeleton. Trabecular deposits of plutonium are gradually shifted to cortical sites. For the dosimetric model some additional features disregarded in the human model were employed. These relate to bone volume labels, a gradation of concentrations in marrow, the energy-dependence of absorbed fractions, and the self-absorption in marrow. The model predicts that the contribution of surface deposits to the endosteal dose still exceeds the contributions from bone volume and marrow labels. The average endosteal dose is about eight times and the marrow dose about two times larger than the average skeletal dose. The model provides the basis for the analysis of survival and relative risks.

Animals↗

Fracture occurrence from radionuclides in the skeleton.

Because skeletal fractures were an important finding among persons contaminated with 226Ra, experience with fractures among dogs in our colony was summarized to determine the projected significance for persons contaminated with bone-seeking radionuclides. Comparison by Fisher's Exact Test of lifetime fracture occurrence in the skeletons of beagles injected as young adults suggested that for animals given 226Ra, 228Ra, 228Th, or 239Pu citrate, there was probably an excess over controls in fractures of the ribs, leg bones, spinous processes, and pelvis (os coxae) plus the mandible for dogs given 226Ra and the scapulae for dogs given 228Ra or 228Th. Regression analysis indicated that significantly elevated fracture occurrence was especially notable at the higher radiation doses, at about 50 Gy average skeletal dose for 239Pu, 140 Gy for 226Ra, about 40 Gy for 228Ra, and more than 15 Gy for 228Th. The average number of fractures per dog was significantly elevated over that noted in controls for the highest radiation doses of 239Pu and 226Ra and for the higher doses of 228Ra and 228Th. For those dogs given 90Sr citrate, there was virtually no important difference from control beagles not given radionuclides, even at group mean cumulative skeletal radiation doses up to 101 Gy. Because of a large proportion of dogs with fractures that died with bone malignancy (even at dosage levels lower than those exhibiting an excess average number of fractures per dog), we conclude that fracture would not be an important endpoint at lower levels of plutonium contamination in humans such as would be expected to occur from occupational or environmental exposure.

Animals↗

Development of an improved dosimetry system for the workers at the Mayak Production Association.

Databases are being created that contain verified and updated dosimetry and worker history information for workers at the Mayak Production Association. Many workers had significant external and internal exposures, particularly during the early years (1948-1952) of operation. These dosimetric and worker history data are to be used in companion epidemiology studies of stochastic and deterministic effects. The database contains both external and internal dose information and is being constructed from other databases that include radiochemical analyses of tissues, bioassay data, air sampling data, whole body counting data, and occupational and worker histories. The procedures, models, methods, and operational uncertainties will be documented and included in the database, technical reports, and publications. The cohort of the stochastic epidemiological study is expected to include about 19,000 persons while the cohort for the deterministic epidemiological study is expected to include about 600 persons. For external dosimetry, workplace gamma, beta, and neutron doses are being reconstructed. The models used for this incorporate issues such as known isotopes, composition, shielding, further analysis of film badge sensitivities, and records of direct measurements. Organ doses from external exposures are also being calculated. Methods for calculating dose uncertainties are being developed. For internal dosimetry, the organ doses have been calculated using the established FIB-1 biokinetic model. A new biokinetic model is being developed that includes more information of the solubility and biokinetics of the different chemical forms and particulate sizes of plutonium that were in the workplace. In addition, updated worker histories will be used to estimate doses to some workers where direct measurements were not made. A rigorous quality control procedure is being implemented to ensure that the correct dosimetry data is entering the various databases being used by the epidemiologists.

Beta Particles↗

Radium-induced eye melanomas in dogs.

The intraocular radiotoxicity of intravenously injected 226Ra and 228Ra was studied in beagle dogs. Approximately 0.071% of injected radium was retained in each eye of beagles following intravenous administration. The retention was principally in the tapetum and the intraocular pigmented structures where significant pigmentary lesions were produced. These included melanotic plaques on the iris, melanosis of the ciliary body, varying degrees of tapetal degeneration, and intraocular melanomas. The tumors occurred principally in the ciliary body and to a much lesser extent in the iris. They appeared to arise from the pigment epithelium layer of the ciliary body. Thus, unlike melanomas arising in other sites, they are apparently not of neural crest origin. In addition to bone cancer, they represent another radium-induced neoplasm in beagles. Radium-induced intraocular melanomas have not been reported in people.

Animals↗

Does body size contribute to sensitivity of bone tumor induction by radionuclide exposure?

Investigation of a possible increase in sensitivity to occurrence of radionuclide-induced skeletal malignancy with increasing body size was analyzed among 358 beagles injected as young adults with either 226Ra or monomeric 239Pu and maintained for their lifespans. Corresponding analyses were performed for about 240 other beagles injected as young adults with 90Sr, 228Ra, or 228Th. Body masses at the time of injection ranged between about 5.6 and 16 kg. Logistic regression analysis using body mass and cumulative skeletal radiation dose as the independent variables indicated that there could not be established a dependency of tumor occurrence upon body mass, although skeletal dose was found to be significantly correlated with occurrence of bone cancer. Regression analysis indicated that for any dosage group there could not be established a correlation between body mass and skeletal dose. Each dosage group having similar injected kBq kg(-1) for each nuclide was divided into 2 subgroups of equal size, one containing the less massive dogs and the other containing the more massive dogs. These subgroups within a roughly uniform value of skeletal dose-rate were compared by Fisher's Exact Test, and the less massive subgroups were combined within each nuclide for an additional, separate analysis against the combined more massive subgroups using the same method. In only one instance (the dosage group given 3607 kBq 90Sr kg(-1)) was there indicated a substantially greater tumor occurrence among dogs in the more massive subgroup (p = 0.061). However, for the group given 0.382 kBq 239Pu kg(-1) there was indicated a significant difference between subgroups, but the effect was exactly opposite to that found for the highest level 90Sr dogs in that the less massive subgroup had a higher relative tumor occurrence than the most massive (p = 0.042). For all groups with a p-value < 0.10, a possible correlation was investigated between survival and body mass at injection (since bone tumor occurrence might be a function of longevity), but a significant relationship could not be determined. No significant differences could be established between the combined more massive and the combined less massive subgroups for any radionuclide. We conclude that, for the conditions in our experiment, relative size within a species does not contribute importantly to the sensitivity (lifetime occurrence) for induction of skeletal malignancy.

Animals↗

Effective thresholds for induction of skeletal malignancies by radionuclides.

Our analysis of data from the beagle project completed at the University of Utah has provided some comparisons that appear to be useful in testing the model proposed by Raabe of effective thresholds for induction of skeletal malignancy by bone-seeking radionuclides in beagles. Raabe's model predicted that cumulative skeletal doses of less than about 0.9 to 1.4 Gy from alpha emitters or 28 to 70 Gy from beta emitters deposited in the skeleton require a long enough time for bone cancer expression that the dog's natural lifespan would be exceeded before the tumor appeared. Results from the Utah beagle project seem to confirm these projections for 226Ra, 228Ra and, perhaps, for 90Sr. The lowest doses at which malignant bone tumors were observed in animals injected with these radium isotopes were about 0.9 Gy (226Ra) and 3 Gy (228Ra). For the beta emitter, 90Sr, the lowest doses at which bone tumors were seen were about 18, 50, and 70 Gy with an expectation for naturally occurring tumor of about one. Twenty-six of the two hundred and thirty-three Utah beagles given monomeric 239Pu that developed skeletal malignancies had doses between 0.02 and 0.51 Gy (80 of these dogs had skeletal doses of less than 0.9 Gy). Three dogs of 54 given 241Am with doses lower than 0.9 Gy had bone tumors at 0.23, 0.56, and 0.88 Gy with the expectation of about one naturally occurring case. For 25 animals injected with 228Th at skeletal doses below 0.9 Gy, one bone tumor dog had a dose of about 0.4 Gy, and the expectation of a dog with natural tumor among the group was only about 0.38. Five beagles of 74 given 224Ra with resulting doses of less than 0.9 Gy died with skeletal malignancy at 0.32 Gy or less with an expectation for non 224Ra induced tumor of about one. It appears that Raabe's proposal might be confirmed for some but not all of the radionuclides used in the Utah studies. Models presented in earlier papers by Raabe provide results that are somewhat different from his recent abstract and compare more favorably with those cited herein for Utah dogs. Re-examination of our data for these analyses has suggested a novel concept for calculation of carcinogenic dose to endosteal bone surfaces.

Americium↗

Mandibular bone formation rates in aged ovariectomized rats treated with anti-resorptive agents alone and in combination with intermittent parathyroid hormone.

Anti-resorptive agents--including estrogen (E), calcitonin (CT), and bisphosphonates--are established in the treatment of osteoporosis. Intermittent administration of parathyroid hormone (PTH) stimulates bone formation and is a possible therapeutic agent for the restoration of bone mass. The purpose was to determine the effects of the anti-resorptive agents alone and in combination with intermittent PTH on bone formation in the mandible and a long bone in the aged ovariectomized (Ovx) rat. Female rats were ovariectomized or sham-operated. One year later, groups of Ovx rats were treated with E, CT, or the bisphosphonate, Risedronate (NE). Additional groups of Ovx rats were treated with each of these agents in combination with human PTH for 10 weeks. Estrogen treatment suppressed most indices of bone formation in the humerus and mandible, while NE decreased some indices of formation at the endocortical and endosteal surfaces of the mandible and humerus. Increased double-labeled surface and mineral apposition rates were observed only on the mandibular endosteal surfaces following CT treatment. When the anti-resorptive agents were combined with intermittent PTH, most indices of bone formation at all skeletal sites were substantially greater than those of the untreated Ovx controls as well as the E-, CT-, and NE-treated groups, respectively. These results provide additional evidence that established and emerging therapies for osteoporosis affect osseous tissues in the oral cavity, and this may influence the progression of diseases and/or aging changes at this site.

Analysis of Variance↗

Histologic changes in the adrenal cortex from young rats following spaceflight.

BACKGROUND: Potential stresses associated with spaceflight include microgravity, acceleration and deceleration forces, a crowded environment and re-adaptation to normal gravity after landing. HYPOTHESIS: We hypothesized that spaceflight would result in histological changes in the adrenal glands of young rats. METHODS: Six week old male rats were group-housed in an Animal Enclosure Module (AEM) for a 17 d shuttle flight (STS-78). Ground-based controls included a baseline group, an AEM-housed group and a vivarium group. Adrenal glands were collected from 4-6 hours after flight, fixed, embedded in plastic and sections prepared for light microscopy. RESULTS: The adrenals from the baseline and vivarium groups had normal histological features. Some changes in the adrenal cortices from the ground-based AEM group included greater parenchymal cord-like formation. The adrenal weights and width of the zona fasciculata were greater in the flight group than the controls. There were also increased parenchymal cord-like formation with better demarcation of the vascular sinusoids in the zona reticularis and zona fasciculata, greater depletion of cytoplasmic lipid vacuoles, and an increased nuclear volume of the cells in the zona fasciculata when compared with the controls. CONCLUSIONS: The adrenal changes in the ground-based AEM animals may be attributed to the confined space in the AEM. The adrenal enlargement and the histological changes observed in the flight animals may be attributed to spaceflight and possibly re-entry in addition to possible confinement stress in the AEM.

Adrenal Cortex↗

Metastable equilibrium solubility behavior of bone mineral.

Previous studies have shown that carbonated apatites with a range of carbonate contents and crystallinities exhibit the phenomenon of metastable equilibrium solubility (MES) distributions. The purpose of the present study was to investigate the solubility behavior of bone mineral using the concepts of MES and MES distributions and, together with crystallinity and chemical composition data, examine the similarity of bone mineral to carbonated apatite (CAP). Bone samples were harvested from 1-, 5-, and 8-month-old rats. The organic components of the bone samples were removed by hydrazine deproteination. Carbonated apatite was synthesized by the hydrolysis of dicalcium phosphate dihydrate (DCPD) in a NaHCO3-containing media at 50 degrees C. The MES distributions of bone mineral and CAP were determined by equilibrating predetermined amounts of CAP or bone mineral in a series of 0.1 M acetate buffers containing calculated levels of calcium and phosphate and maintained at essentially constant pHs of 5.0, 5.3, 5.7, and 6.5. From the compositions of the equilibrating buffer solutions, ion activity products based upon the stoichiometries of octacalcium phosphate, hydroxyapatite, and carbonated apatite were calculated in an attempt to determine the function governing the dissolution of CAP and bone mineral. The results of this study demonstrated that the MES distribution phenomenon appeared to hold for bone mineral and that the changes in crystallinity of bone mineral with age correlated well with changes in the MES values. A CAP sample was prepared that was found to be an excellent synthetic prototype closely mimicking the physicochemical behavior of bone mineral from an 8-month-old rat. Another finding of this study was that the ion activity product function based upon the hydroxyapatite stoichiometry well described the MES results obtained with both CAP and bone mineral. The interpretation that a surface complex with hydroxyapatite stoichiometry governs the solubility behavior of bone mineral is, therefore, consistent with the experimental data. Other calcium phosphate stoichiometries for the surface complex showed systematic variations in the MES profiles when the pH of the equilibrating solution was varied.

Age Factors↗

Dual activity of pyrrolidine dithiocarbamate on kappaB-dependent gene expression in U937 cells: II. Regulation by tumour necrosis factor-alpha.

In the human promonocytic U937 cell line, pyrrolidine dithiocarbamate (PDTC) was a potent inhibitor of the nuclear factor-kappaB (NF-kappaB) signalling pathway induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). However, PDTC did not inhibit tumour necrosis factor-alpha (TNF-alpha)-induced NF-kappaB DNA binding activity but potentiated the effect of TNF-alpha on kappaB-dependent gene expression. The stimulatory effect of PDTC with TNF-alpha was not observed with an HIV-1 LTR reporter construct containing two mutated kappaB binding sites or with a construct with a mutation of the activating protein (AP)-2 binding site located between the two kappaB elements. Two distinct signalling pathways, one mediated by TPA and the other by TNF-alpha, were shown to interact, functionally defining a threshold important in the inhibitory or stimulatory effect of PDTC on kappaB-dependent gene expression. Evidence that PDTC induced AP-1 DNA binding and AP-1 reporter gene activity, raised the hypothesis that the effect of PDTC was mediated by an interaction between the AP-1 pathway and p65(RelA). Co-transfection with expression vectors for p65(RelA) and the AP-1 subunits c-Fos and c-Jun resulted in a decrease in the stimulatory effect of PDTC on HIV-1 LTR activity. Co-transfection of p65(RelA) with Tam67, a dominant negative mutant of c-Jun defective in transactivation, stimulated the effect of PDTC on HIV-1 LTR activity. Evidence that the stimulatory effect of Tam67 with PDTC was reduced with c-Jun is consistent with the hypothesis.

Binding Sites↗

Dual activity of pyrrolidine dithiocarbamate on kappa B-dependent gene expression in U937 cells: I. Regulation by the phorbol ester TPA.

Pyrrolidine dithiocarbamate (PDTC) has been widely used as an inhibitor of the nuclear factor-kappa B, (NF-kappa B) signalling pathway. Here, we show that kappa B-dependent reporter gene expression induced by low concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA) is potentiated by PDTC in the human pro-monocytic U937 cell line. The stimulatory effect of PDTC on kappa B-dependent gene expression was shown with a 4 x kappa B chloramphenicol acetyltransferase construct and required an intact kappa B element in the human immunodeficiency virus long terminal repeat (HIV-1 LTR). Unexpectedly, an HIV-1 LTR construct with a mutation of the activator protein 2 (AP-2) binding site located between the two kappa B elements was unresponsive to the stimulatory effect of PDTC with TPA. The stimulation or inhibition of kappa B-dependent gene expression was dependent on PDTC pre-treatment and the concentration of TPA. No stimulatory effect on HIV-1 LTR activity was observed with the metal chelator dipyridyl or the anti-oxidant N-acetyl-L-cysteine. These results are consistent with the hypothesis that PDTC treatment potentiated kappa B-dependent gene expression in a manner dependent on the concentration of TPA.

Chelating Agents↗

Skeletal mass, chemistry, and growth during and after multiple reproductive cycles in the rat.

There are dramatic changes in skeletal physiology and metabolism to accommodate the mineral requirements of the developing fetus during pregnancy and milk production during lactation. The purpose of this study was to document changes in skeletal growth, chemistry, and mass during and after multiple reproductive cycles in the rat, with emphasis on the putative reconstitution of the skeleton after lactation. To determine skeletal changes, experimental groups included rats at the end of the first and second lactation, at the end of the second pregnancy, and at various times after the first and second lactation. These groups were also compared with aged-matched, nulliparous animals. There were decreases in femoral ash weights and bone mineral densities (BMDs) during the first and second lactations, but accelerated rates of gain after lactation, compared with the nulliparous controls. The changes in bone ash were even more pronounced when normalized to the maternal body weight changes during and after the reproductive cycles. The rates and amount of bone mineral (ash) gain after the first and second reproductive cycles were similar; however, neither bone mineral nor BMD returned to levels found in nulliparous animals after the first and subsequent reproductive cycle. There was also a decrease in ash/dry weight ratio of the femur during the second lactation, suggesting a preferential loss of more mineralized bone. This decrease in ash/dry weight ratio reversed after lactation, indicating a relative accumulation of bone mineral during the postlactational period. As expected, endochondral growth was substantially suppressed during lactation, but rebounded during the postlactational period. These data collectively support the notion that the female rat has excess skeletal mass to accommodate losses associated with the first reproductive cycle. After the first reproductive cycle, a new optimal skeletal mass is achieved. These data also demonstrate that the postlactational period is "anabolic" with accelerated rates of bone growth and accumulation of bone mineral and bone mineral density with increases in the ratios of the inorganic to organic composition of the bone. This postlactational recovery phase may serve to at least partially reconstitute skeletal mineral depleted during lactation and perhaps to prepare the skeleton for the next reproductive cycle.

Animals↗

The American coneflower: a prophylactic role involving nonspecific immunity.

OBJECTIVE: In humans, considerable circumstantial evidence exists that indicates soluble root extracts of the American coneflower, genus Echinacea, may act to ameliorate virus-mediated afflictions, such as the common cold, influenza, and even AIDS and virus-based tumors. This study was designed to quantify, in normal mice, Echinacea-mediated, quantitative, dynamic changes, with time on both mature and precursor cells, of all the hemopoietic and immune-cell lineages in the spleen and bone marrow. DESIGN: A specific, commercially prepared potent extract of Echinacea root was provided daily in the diet for either 1 week or 2 weeks with the aim of establishing a possible mechanism of action for this herb. RESULTS: The data revealed that natural-killer (NK) cells and monocytes, both mediators of nonspecific immunity and well-demonstrated killers of virus-containing cells, were numerically and significantly increased in both the bone marrow and the spleen as early as 1 week after beginning treatment with the dietary herb. In contrast to our observations with NK cells and monocytes, the sizes of all other hemopoietic and immune cell populations in these two organs remained at control levels even after 2 weeks of daily dietary Echinacea. CONCLUSIONS: The work has demonstrated the specific nature of Echinacea-derived phytochemicals in acting as stimulants of those cells responsible for nonspecific immunity, as the first line of defense against virus-infected/transformed cells. The observations that these cells were elevated in the bone marrow indicates that at least one mechanism of action of this herb, is to stimulate new cell production in situ. The significant elevation of these two fundamental immune-cell populations, in normal animals, suggests a prophylactic role for this herb.

Animals↗

Nursing home admission for African Americans with Alzheimer's disease.

BACKGROUND: For African Americans with Alzheimer's disease (AD), little is known about the time to, and risk factors for, nursing home admission (NHA). Using Consortium To Establish a Registry for Alzheimer's Disease (CERAD) data, this study provides information on NHA for African Americans. METHODS: This longitudinal study followed subjects (N=122) for as long as 7 years and used survival analysis methodology and variable values at baseline and at follow-up to identify NHA risk factors. Studied were sociodemographic variables, physical symptom and disease status variables, the Blessed Dementia Rating Scale (including subscores), the Clinical Dementia Rating (CDR), and the Mini-Mental State Examination. RESULTS: Only 25% of African Americans with AD were estimated to have had a NHA by 3.4 years (confidence interval 2.1, 5.4). Being unmarried resulted in a five times earlier NHA (p< .01), and each unit increase in the CDR resulted in a 74% earlier NHA (p<.01). In the absence of the CDR, limitation in activities of daily living was associated with earlier NHA (p<.05). CONCLUSIONS: Findings suggest that African Americans with AD spend a substantial time in the community prior to NHA, a longer time than observed in similar studies among whites. This raises public health and clinical concern that African Americans with AD may be residing in the community with substantial unmet needs, and that their caregivers have potentially high levels of burden. The independent associations with time to NHA observed here, although few in number, are consistent with other related research.

Aged↗

Increased intracortical bone remodeling during lactation in beagle dogs.

There are substantial changes in skeletal and mineral metabolism during pregnancy and lactation. The purpose of this study was to determine the changes in intracortical bone remodeling and turnover during lactation in beagle dogs. A femur and rib were obtained from dogs near the end of lactation or soon after weaning and compared with nonlactating controls. Rib cortical bone had much higher bone turnover rates than did femoral diaphyseal cortical bone. The number of single-labeled osteons and the number of resorption spaces were significantly greater during lactation in both the rib and the femur. Additionally, the mineral apposition rate, basic multicellular unit activation frequency, and bone turnover rates were greater in the femoral cortical bone from the lactating dogs than from the controls. These data demonstrate that during lactation, intracortical bone remodeling increases, and this may provide a mechanism for the skeleton to be responsive to the calcium requirements of the mother. In addition, these data may help explain the transient decreases in cortical bone mineral density that are reported to occur during human lactation.

Animals↗