Biomedical subjects

M A Lane

Publications and source records attributed to M A Lane.

At least 37 records · Page 2Linked to original sources

PubMed2001

Aging and caloric restriction in nonhuman primates: behavioral and in vivo brain imaging studies.

In a long-term longitudinal study of aging in rhesus monkeys, a primary objective has been to determine the effects of aging and caloric restriction (CR) on behavioral and neural parameters. Through the use of automated devices, locomotor activity can be monitored in the home cages of the monkeys. Studies completed thus far indicate a clear age-related decline in activity consistent with such observations in many other species, including humans. However, no consistent effects of CR on activity have been observed. Selected groups of monkeys have also been involved in brain imaging studies, using magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI studies completed thus far reveal a clear age-related decline in the volumes of the basal ganglia, the putamen, and the caudate nucleus, with no change in total brain volume. PET analysis has revealed an age-related decline in the binding potential of dopamine D2 receptors in the same brain regions. These results are consistent with findings in humans. Although additional longitudinal analysis is needed to confirm the present results, it would appear that locomotor activity, volume of the basal ganglia, as well as dopamine D2 receptor binding potential provide reliable, noninvasive biomarkers of aging in rhesus monkeys.

Aging↗

PubMed2001

Cryptosporidium parvum infection requires host cell actin polymerization.

The intracellular protozoan parasite Cryptosporidium parvum accumulates host cell actin at the interface between the parasite and the host cell cytoplasm. Here we show that the actin polymerizing proteins Arp2/3, vasodilator-stimulated phosphoprotein (VASP), and neural Wiskott Aldrich syndrome protein (N-WASP) are present at this interface and that host cell actin polymerization is necessary for parasite infection.

Actin-Related Protein 2↗

PubMed2001

Dietary caloric restriction prevents the age-related decline in plasma melatonin levels of rhesus monkeys.

Rhesus monkeys exhibit an age-associated decrease in peak plasma melatonin levels analogous to that reported for humans. This decrease is essentially abolished in monkeys subjected to a 30% reduction in caloric intake over a 12-yr period. The caloric restriction (CR) effect does not seem to be a reversal, but rather a long-term prevention, of the age-related decline in hormone concentrations. The age effect does not seem to be due to a phase shift in the peak of melatonin secretions, as has been observed in some populations of aged humans. It is also extremely unlikely that the CR effect simply reflects a phase shift, since old monkeys on the diet have nocturnal melatonin levels equal to or greater than adult fully fed controls. Thus, if peak times (approximately 0200 h) were actually shifted, maximal levels in old CR monkeys would be even higher. These findings, coupled with previous observations in humans, suggest that peak plasma melatonin levels may represent a possible candidate "biomarker of aging" in primates. Moreover, this index of age-associated physiological decrement seems to be inhibited by dietary CR.

Aging↗

PubMed2000

Interoperability of biodiversity databases: biodiversity information on every desktop.

Data about biodiversity are either scattered in many databases or reside on paper or other media not amenable to interactive searching. The Global Biodiversity Information Facility (GBIF) is a framework for facilitating the digitization of biodiversity data and for making interoperable an as-yet-unknown number of biodiversity databases that are distributed around the globe. In concert with other existing efforts, GBIF will catalyze the completion of a Catalog of the Names of Known Organisms and will develop search engines to mine the vast quantities of biodiversity data. It will be an outstanding tool for scientists, natural resource managers, and policy-makers.

Animals↗

PubMed2000

Fetuin in the developing neocortex of the rat: distribution and origin.

Immunocytochemical distribution of the fetal protein fetuin in the neocortex of developing rat brain and the presence of its mRNA, as detected by using reverse transcriptase-polymerase chain reaction analysis, was studied in fetuses at embryonic day 15 (E15) through E22, in neonates at postnatal day 0 (P0) through P20, and in adults. Quantitative estimates of fetuin in cerebrospinal fluid (CSF) and plasma were obtained over the same period. Exogenous (bovine) fetuin injected intraperitoneally into fetal and postnatal rats was used to study the uptake of fetuin into CSF and brain and its distribution compared with endogenous fetuin; bovine albumin was used as a control. Fetuin was identified immunocytochemically in the cortical plate and subplate cells of the developing neocortex. In the rat fetus, fetuin first was apparent at E17, mainly in cell processes, but a few subplate cells also were positive. By E18, there was strong staining in subplate neurons and in inner cells of the cortical plate. At E21, these inner cells of the cortical plate were beginning to differentiate into layer VI neurons, many of which were positive for fetuin. By P0-P1, more layer VI neurons and some layer V neurons had become positive for fetuin. Fetuin immunoreactivity generally was weaker at P1, and, by P2-P3, it had disappeared from all of the layers of the developing neocortex. Bovine fetuin (but not albumin), probably taken up through CSF over the neocortical dorsal surface, had a cytoplasmic distribution; endogenous rat fetuin was both cytoplasmic and membrane bound. Thus, much of this fetuin can be accounted for by uptake, although the presence of fetuin mRNA indicates that in situ synthesis may also contribute.

Animals↗

PubMed2000

Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta).

Calorie restriction (CR) is widely known for its effects on life span, physiological aging and age-related disease in laboratory rats and mice. Emerging data from CR studies in rhesus monkeys suggest that this nutritional intervention paradigm may also have beneficial effects in long-lived mammals. Studies from our laboratory and others have suggested that young- or adult-onset CR might have beneficial effects on cardiovascular disease and diabetes. For example, long-term CR reduced body fat and serum triglycerides, and increased a subfraction of HDL cholesterol associated with decreased cardiovascular disease risk. These studies suggested that long-term CR begun in young or adult animals might have important effects on markers relevant to age-related disease. Few studies have examined the effects of CR initiated in older animals (rodents or monkeys), and the temporal nature of some potentially beneficial effects of CR is unknown. The present study examined several markers related to diabetes and cardiovascular disease in thirteen older adult (> 18 year) non-obese (body fat < 22%), male rhesus monkeys during a short-term CR paradigm. Specifically, we collected these data at baseline (ad libitum feeding), 10, 20, and 30% CR, and at 6 and 12 months on 30% CR. Fasting and peak insulin were significantly reduced as were the acute and second-phase insulin responses. CR also marginally reduced triglycerides (50% reduction), but had no effect on total serum cholesterol or blood pressure. Interestingly, the observed glucoregulatory changes emerged prior to any evidence of a change in body composition suggesting that certain effects of CR may not be wholly dependent on changes in body composition in older monkeys.

Aging↗

PubMed2000

Acute-phase cytokines IL-1beta and TNF-alpha in brain development.

The nervous and the immune systems share several molecules that control their development and function. We studied the temporal and spatial distribution of the immunoreactivity of two acute-phase cytokines, TNF-alpha and IL-1beta, in the developing sheep neocortex and compared it with the well-described distribution of fetuin, a fetal glycoprotein also known to modulate the production of cytokines by lipopolysaccharide (LPS)-stimulated monocytes and macrophages. TNF-alpha was present first at embryonic day 30 (E30) (term is 150 days in sheep) as a faint band of immunoreactivity between the ventricular zone and the primordial plexiform layer (preplate). IL-1beta was detected at the first appearance of the cortical plate (E35-E40). Both cytokines were present on both sides of the cortical plate, which contained fetuin-positive cells, but was free from cytokine staining. By E60, TNF-alpha immunoreactivity was less prominent than that of IL-1beta and was confined to the marginal zone and outer developing white matter; IL-1beta was present in the marginal zone and in two bands of immunoreactive cells, one at the border of the cortical plate/developing layer VI (cells of neuronal morphology) and the other at the border of layer V and the developing white matter (identified as microglia). By E80, TNF-alpha staining had disappeared and IL-1beta-immunopositive microglia were no longer detectable. By E100-E140 only a few immunoreactive cells were identified in layers V-VI; these did not co-localize with fetuin-positive cells. The differences in distribution between fetuin and the two cytokines suggest that the opsonizing role of fetuin, proposed for monocyte production of cytokines, is probably not present in the developing brain. However, early in neocortical development TNF-alpha and IL-1beta were present in the subplate zone at a time of intense synaptogenesis.

Acute-Phase Reaction↗

PubMed2000

Nonhuman primate models in biogerontology.

A variety of animal models are utilized in biogerontological studies including yeast, nematodes, fruit flies, hamsters, mice, rats, and nonhuman primates. Species selection for research is based on many factors including economic feasibility, husbandry, generalizability of findings, available background information, adaptability to experimentation, and often, relevance to human aging. Each model offers its own strengths and limitations; however, nonhuman primates offer the unique advantage of phylogenetic proximity to humans. Among others, costs to purchase and maintain research subjects represent major limitations of nonhuman primate models. Although several nonhuman primate species have been utilized in aging research, rhesus monkeys (Macaca mulatta) are the best characterized and most extensively studied in biomedical gerontology. Nonhuman primate models have been employed as models for human aging in many research areas including neurobiology, skeletal, and reproductive aging and age-related diseases such as cardiovascular disease and diabetes. Primate models are now also being utilized to study interventions into aging such as caloric restriction. It will be several more years until definitive conclusions regarding lifespan effects can be made. However, existing data strongly suggest that many of the beneficial effects reported in rodents on CR also occur in primate models thereby strengthening the possibility that this nutritional paradigm may also impact favorably upon human aging.

Aging↗

PubMed2000

Effects of reduced energy intake on the biology of aging: the primate model.

Dietary energy restriction is the only proven method for extending lifespan and slowing aging in mammals, while maintaining health and vitality. Although the first experiments in this area were conducted over 60 y ago in rodents, possible applicability to primates has only been examined in controlled studies since 1987. Our project at the National Institute on Aging began with 3-0 male rhesus and 30 male squirrel monkeys of various ages over their respective life spans. Subsequently, it has been expanded to include female rhesus monkeys, and several other laboratories have initiated related studies. Experimental animals are generally fed 30% less than controls, and diets are supplemented with micronutrients to achieve undernutrition without malnutrition. These calorically restricted (CR) monkeys are lighter, with less fat and lean mass than controls. Bone mass is also slightly reduced, but in approximate proportion to the smaller body size. CR animals mature more slowly and achieve shorter stature than controls as well. Metabolically, CR monkeys have slightly lower body temperature and initial energy expenditure following onset of restriction, and better glucose tolerance and insulin sensitivity. The latter suggest a reduced predisposition towards diabetes as the animals age. Other potential anti-disease effects include biomarkers suggestive of lessened risk of cardiovascular disease and possibly cancer. Candidate biomarkers of aging, including the age-related decrease in plasma dehydroepiandrosterone sulfate (DHEAS), suggest that the CR animals may be aging more slowly than controls in some respects, although sufficient survival data will require more time to accumulate. In summary, nearly all CR effects detected in rodents, which have thus far been examined in primates, exhibit similar phenomenology. Potential applicability of these beneficial effects to humans is discussed.

Aging↗

PubMed2000

Locomotor activity in female rhesus monkeys: assessment of age and calorie restriction effects.

As a component of a long-term, longitudinal study of aging in this primate model, the objective of the current experiment was to assess age and diet effects on locomotor activity in a cross-sectional analysis. By attaching a motion detection device to the home cage, locomotor activity was monitored over a week in a group (N = 47) of female rhesus monkeys (Macaca mulatta) 6-26 yrs of age. About half these monkeys composed a control group fed a nutritionally fortified diet near ad libitum levels, whereas an experimental group had been fed the same diet at levels 30% less than comparable control levels for approximately 5 yrs prior to testing. Among control monkeys, a marked age-related decline in activity was noted when total activity was considered and also when diurnal and nocturnal periods of activity were analyzed separately. When comparing activity levels between control and experimental groups, only one significant diet effect was noted, which was in the youngest group of monkeys (6-8 yrs of age) during the diurnal period. Monkeys in the experimental group exhibited reduced activity compared to controls. Body weight was not consistently correlated to activity levels. In some older groups, heavier monkeys tended to show greater activity, but in younger groups the opposite pattern was observed.

Age Factors↗

PubMed2000

Are adolescents being screened for sexually transmitted diseases?

OBJECTIVES: To determine the proportion of sexually experienced African American adolescents who report having been screened for sexually transmitted diseases and to determine the proportion who report having been screened for these diseases among adolescents who have had a preventive primary health care visit in the past 2 years. METHODS: A telephone survey of a population-based sample of African American adolescents aged 12 to 17 years residing in a low-income neighborhood in San Francisco with a high prevalence of sexually transmitted diseases. RESULTS: Of the 302 adolescents surveyed, 118 (39.1%) reported a history of sexual intercourse. Of these, 17 (26. 2%) of 65 males and 31 (58.5%) of 53 females had been screened for a sexually transmitted disease in the previous 12 months. Twenty (30. 8%) of the males and 32 (60.4%) of the females had been screened for a sexually transmitted disease in the previous 24 months. Of the 93 participants who had a preventive primary care visit since their first episode of sexual intercourse, 14 (26.4%) of the 53 males and 24 (60.0%) of the 40 females had been screened for a sexually transmitted disease in the previous 24 months. CONCLUSIONS: Sexually experienced African American adolescents in San Francisco are being screened for sexually transmitted diseases at rates well below those recommended by current clinical guidelines. A low rate of screening was found even in adolescents who had been seen for a preventive primary care visit since they had first had sex. This suggests that the preventive primary care visit is not being used to its full potential as an opportunity to screen and treat adolescents for sexually transmitted diseases. Capitalizing on this opportunity to screen may increase the number of cases of sexually transmitted diseases diagnosed and, thus, decrease rates of these diseases in this population.

Adolescent↗

PubMed2000

Are adolescents being screened for sexually transmitted diseases? A study of low income African American adolescents in San Francisco.

OBJECTIVES: To determine the proportion of sexually experienced African American adolescents who report having been screened for sexually transmitted diseased (STDs), and to determine the proportion who report having been screened for STDs among those adolescents who have had a preventive primary healthcare visit in the past 2 years. METHODS: A telephone survey of a population based sample of African American 12-17 year old adolescents residing in a low income San Francisco neighbourhood with a high prevalence of STDs. RESULTS: Of the 302 adolescents surveyed, 118 (39%) reported a history of sexual intercourse. Of these, 26% of the males and 59% of the females had been screened for an STD in the previous 12 months. 31% of the males and 63% of the females had been screened for an STD in the previous 24 months. Of the 93 participants who had had a preventive primary care visit since their first episode of sexual intercourse, 26% of the males and 60% of the females had been screened for an STD in the previous 24 months. CONCLUSIONS: Sexually experienced African American adolescents in San Francisco are being screened for STDs at rates well below that recommended by current clinical guidelines. A low rate of screening was found even in those adolescents who had been seen for a preventive primary care visit since they first had sex. This suggests that the preventive primary care visit is not being used to its full potential as an opportunity to screen and treat adolescents for STDs. Capitalizing on this opportunity to screen may increase the number of STDs diagnosed and, thus, decrease rates of STDs in this population.

Adolescent↗

PubMed2000

Sheep rumen metabolic development in response to age and dietary treatments.

This study examined the time course of rumen metabolic development in the absence of solid feed consumption and the effect of delayed solid feed consumption on sheep rumen development. Twenty-seven lambs consumed milk replacer until slaughter at nine ages from 1 to 84 d (milk group). Three additional lambs consumed milk replacer from 1 to 48 d. From 49 d until slaughter at 84 d, these lambs were weaned onto solid feed (fed group). At slaughter, rumen contents were removed for VFA analysis and rumen epithelium was preserved for morphological examination. Rumen epithelial cells were isolated and incubated in media containing 2.5 mM U-[14C]-glucose or 10 mM 1-[14C]-butyrate. Rumen VFA concentrations did not change with age in lambs given milk replacer. At 84 d of age, intraruminal VFA concentrations were elevated in lambs consuming solid feed compared to 84-d-old lambs given milk replacer (P < .05). The number of ruminal papillae per square centimeter decreased (P < .05) while papillae length and width did not change significantly with age in rumen epithelium from lambs given milk replacer. At 84 d of age, rumen epithelium from lambs in the fed group had fewer and larger papillae/per square centimeter than rumen epithelium from lambs given milk replacer (P < .05). Rates of glucose and butyrate oxidation and acetoacetate and lactate production by rumen cells isolated from lambs given milk replacer did not change with age. Beta-hydroxybutyrate (BHBA) production was undetectable before 42 d of age in lambs given milk replacer and increased to levels found in conventionally raised adults by 84 d. At 84 d there were no differences in rates of glucose and butyrate oxidation or acetoacetate and lactate production by rumen cells between the two treatment groups. Thus, the change in substrate oxidation from glucose to butyrate, indicative of rumen metabolic maturation, does not occur in the absence of solid feed consumption. However, the development of rumen ketogenesis, as evidenced by increased BHBA production, does occur in the absence of solid feed consumption. Delaying the initiation of solid feed consumption results in rumen morphological development but does not stimulate rumen metabolic development. Increased intraruminal VFA concentrations, earlier exposure to VFA, or a longer period of exposure to VFA may be required to induce the genes responsible for rumen metabolic development.

Aging↗

PubMed1999

Removal of LIF (leukemia inhibitory factor) results in increased vitamin A (retinol) metabolism to 4-oxoretinol in embryonic stem cells.

Retinoids, vitamin A (retinol) and its metabolic derivatives, are required for normal vertebrate development. In murine embryonic stem (ES) cells, which remain undifferentiated when cultured in the presence of LIF (leukemia inhibitory factor), little metabolism of exogenously added retinol takes place. After LIF removal, ES cells metabolize exogenously added retinol to 4-hydroxyretinol and 4-oxoretinol and concomitantly differentiate. The conversion of retinol to 4-oxoretinol is a high-capacity reaction because most of the exogenous retinol is metabolized rapidly, even when cells are exposed to physiological ( approximately 1 microM) concentrations of retinol in the medium. No retinoic acid or 4-oxoRA synthesis from retinol was detected in ES cells cultured with or without LIF. The cytochrome P450 enzyme CYP26 (retinoic acid hydroxylase) is responsible for the metabolism of retinol to 4-oxoretinol, and CYP26 mRNA is greatly induced (>15-fold) after LIF removal. Concomitant with the expression of CYP26, differentiating ES cells grown in the absence of LIF activate the expression of the differentiation marker gene FGF-5 whereas the expression of the stem cell marker gene FGF-4 decreases. The strong correlation between the production of polar metabolites of retinol and the differentiation of ES cells upon removal of LIF suggests that one important action of LIF in these cells is to prevent retinol metabolism to biologically active, polar metabolites such as 4-oxoretinol.

Animals↗

PubMed1999

Features of sexually transmitted disease services important to African American adolescents.

OBJECTIVE: To determine the relative importance of various features of health clinics when African American adolescents consider seeking care for sexually transmitted diseases (STDs). DESIGN: Confidential interviewer-administered telephone survey. SETTING: A predominantly low-income, African American neighborhood in San Francisco, Calif. PARTICIPANTS: Random sample of African American adolescents aged 12 to 17 years; 302 (76.6%) of 394 identified eligible adolescents participated. MAIN OUTCOME MEASURES: Items and scales measuring adolescents' sense of the importance of the attributes of the provider (alpha = .58), availability of services (alpha = .61), and perceived confidentiality of health services from family (alpha = . 72) when deciding where to seek care for possible STDs. RESULTS: More than 90% (90.4%) of subjects rated items relating to provider attributes as being highly important when they consider where they would seek care for an STD; between 62.5% and 82.7% rated availability items as being highly important; and between 38.6% and 60.8% rated items pertaining to confidentiality as being highly important. Greater importance was placed on provider attributes and confidentiality by female than male adolescents. The importance placed on provider attributes and confidentiality increased as adolescents aged. CONCLUSIONS: Low-income, African American adolescents place great importance on provider attributes, less importance on availability, and even less importance on confidentiality when deciding where to seek health care for a possible STD. Health care providers and organizations need to be aware of these adolescent preferences to better promote screening and treatment of STDs in this population.

Adolescent↗

PubMed1999

Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta).

Caloric restriction (CR) is the most successful method of extending both median and maximal lifespans in rodents and other short-lived species. It is not yet clear whether this method of life extension will be successful in longer-lived species, possibly including humans; however, trials in rhesus monkeys are underway. We have examined the cellular proliferative potential of cells from CR and AL (ad libitum fed) monkey skin cells using two different bioassays: colony size analysis (CSA) of dermal fibroblasts isolated and cloned directly from the skin and beta-galactosidase staining at pH 6.0 (BG-6.0) of epidermal cells in frozen sections of skin. Decreases in both proliferative markers occurred with age, but no differences were observed between CR and AL animals. Skin biopsies were obtained from AL and CR rhesus monkeys from two different aging colonies, one at the National Institute on Aging (NIA) and one at the University of Maryland-Baltimore (UMB). These biopsies were used as a source of tissue sections and cells for two biomarkers of aging assays. The CR monkeys had been maintained for 9-12 years on approximately 70% of the caloric intake of control AL animals. In the CSA studies, the fraction of small clones increased significantly and the fraction of large clones decreased significantly with increasing age in AL monkeys. The frequency of epidermal BG-6.0 staining cells increased with age in older (>22 years) AL monkeys, but most predominately in those of the UMB colony, which were somewhat heavier than the NIH AL controls. Old monkeys on CR tended to have fewer BG-6.0-positive cells relative to old AL-derived epidermis, but this effect was not significant. These results indicate that cellular proliferative potential declined with age in Macaca mulatta, but was not significantly altered by CR under these conditions. Although these experiments are consistent with an absence of effect of CR on monkey skin cell proliferative potential, we have found in previous experiments with mice that a longer duration of CR (as a fraction of total lifespan) was needed to demonstrate CR-related improvement in clone size in mice. Further studies on the now mid-aged monkeys will be needed as their age exceeds 20 years to conclusively rule out an effect of CR on proliferative potential of skin cells from these primates.

Aging↗

PubMed1999

Skeletal effects of aging in male rhesus monkeys.

Age-related bone loss in men is receiving increased attention. In light of this, animal models for male bone loss are desirable. This study examined the effects of age and osteoarthritis (OA) on bone mineral content (BMC), bone mineral density (BMD), and markers of bone turnover and skeletal relevance in 56 male rhesus monkeys 4-34 years of age. BMC and BMD increased at all sites from 4 to 10 years of age. Male rhesus monkeys reach peak bone mass at approximately 10 years of age after which bone mass is lower at the lateral spine and distal radius. Markers of bone turnover (osteocalcin and carboxyterminal telopeptide of type I collagen [ICTP]) decreased with age. There was no relationship between PTH, 25-hydroxyvitamin D, FSH, or testosterone and age. With advancing age, the prevalence of lumbar spine OA increases dramatically, masking decreases in posteroanterior spine bone mass that are clear in the lateral projection. These data suggest that male rhesus monkeys sustain age-related bone loss in the absence of nutritional or gonadal steroid deficiencies. These animals may prove useful in studying the mechanisms of age-related bone loss.

25-Hydroxyvitamin D 2↗

PubMed1999

Calorie restriction in nonhuman primates: effects on diabetes and cardiovascular disease risk.

The effects of calorie restriction (CR) on life span, disease, and aging in physiological systems have been documented extensively in rodent models. However, whether CR has similar effects in longer-lived species more closely related to humans remains unknown. Studies of CR and aging using nonhuman primates (rhesus monkeys) have been ongoing for several years at the National Institute on Aging and the University of Wisconsin-Madison. The majority of data published from these studies are consistent with the extensive findings reported in rodents. For example, monkeys on CR weigh less and have less body fat. Monkeys on CR also exhibit lower body temperature, fasting blood glucose and insulin, and serum lipids. In addition, insulin sensitivity is increased in monkeys on CR. Recent efforts in the NIA study have focused on the effect of this intervention on risk factors for various age-related diseases, in particular for diabetes and cardiovascular disease. We have shown that monkeys on CR have lower blood pressure, reduced body fat, and a reduced trunk:leg fat ratio. Also, monkeys on CR have reduced triglycerides and cholesterol and have increased levels of HDL2B. Low levels of this HDL subfraction have been associated with increased cardiovascular disease in humans. In short-term studies, older (> 18 years) monkeys on CR exhibit reductions in insulin and triglycerides before changes in body composition and fat distribution became evident. These and other findings have suggested that CR might have beneficial effects on certain disease risk factors independent of reductions in body weight or prevention of obesity.

Aging↗