Can colour vision re-evolve? Variation in the X-linked opsin locus of cathemeral Azara's owl monkeys (Aotus azarae azarae).

BACKGROUND: Do evolutionary specializations lead to evolutionary constraint? This appears plausible, particularly when specialization leads to loss of complex adaptations. In the owl monkey lineage, nocturnality clearly arose from a diurnal ancestor. This behavioural shift was accompanied by morphological changes in the eye and orbit and complete loss of colour vision via missense mutations in the gene encoding the short-wave sensitive visual pigment (SWS opsin). Interestingly, at least one subspecies of owl monkey, Azara's owl monkey (Aotus azarae azarae), has regained activity in daylight. Given that all primate species that are active in daylight, including primarily diurnal species and species that are active during both day and night, have at least dichromatic colour vision, it seems reasonable to propose that dichromacy would be adaptive in A. a. azarae. With a disabled SWS opsin, the main avenue available for Azara's owl monkeys to re-evolve colour vision is via a polymorphism in the intact X-linked opsin locus, which commonly occurs in other New World monkeys. To examine this possibility we assayed variation in the X-linked opsin of A. a. azarae, focusing on the three exons (3, 4 and 5) that control spectral sensitivity. RESULTS: We found low opsin genetic variation on a population level, and no differences at the three main sites that lead to variation in spectral sensitivity in the opsins of other New World monkeys. Two rare alleles with single amino acid variants are segregating in the population, but previous functional studies indicate that these are unlikely to affect spectral sensitivity. CONCLUSIONS: Genetic constraint on the re-evolution of colour vision is likely operating in Azara's owl monkey, which may affect the niche that this subspecies is able to occupy.

Major histocompatibility complex and microsatellite variation in two populations of wild gorillas.

In comparison to their close relatives the chimpanzees and humans, very little is known concerning the amount and structure of genetic variation in gorillas. Two species of gorillas are recognized and while the western gorillas number in the tens of thousands, only several hundred representatives of the mountain gorilla subspecies of eastern gorillas survive. To analyse the possible effects of these different population sizes, this study compares the variation observed at microsatellite and major histocompatibility complex (MHC) loci in samples of wild western and mountain gorillas, collected using a sampling scheme that targeted multiple social groups within defined geographical areas. Noninvasive samples proved a viable source of DNA for sequence analysis of the second exon of the DRB loci of the MHC. Observed levels of variation at the MHC locus were similar between the two gorilla species and were comparable to those in other primates. Comparison of results from analysis of variation at multiple microsatellite loci found only a slight reduction in heterozygosity for the mountain gorillas despite the relatively smaller population size.

Levels of selection, altruism, and primate behavior.

Altruistic behaviors seem anomalous from a traditional view of Darwinian natural selection, and evolutionary explanations for them have generated much discussion. The debate centers around four major explanations: classic individual-level selection, reciprocity and game theory, kin selection, and trait-group selection. The historical context and defining criteria of each model must be reviewed before its validity can be assessed. Of these proposed mechanisms, group selection historically has been the most controversial. Although the extent to which empirical data support group selection hypotheses is uncertain, there is evidence for group-level selection among avirulent virus strains and foraging ant queens. Researchers studying mammalian behavior, particularly primatologists, have largely dismissed models of group-level selection. Most discussion of altruism among primates has focused on differences in fitness among individuals within a single group, but students of altruistic behaviors exhibited by primates also need to investigate intergroup variation with respect to these behaviors. Various altruistic behaviors are likely to have evolved through different forms of selection, and each example of apparent altruism therefore needs to be evaluated separately.

A block rotation in community pediatrics.

OBJECTIVES: To develop, implement, and evaluate a 1-month block rotation in community pediatrics. INTERVENTIONS: Faculty from University of California San Diego and Naval Medical Center San Diego developed a combined and integrated curriculum for second-year residents in community pediatrics. Resident activities included structured site visits to schools, day care centers, and community organizations that participate in child health promotion, advocacy, public health, and prevention activities. Resident school consultation and child advocacy projects were established and mentored during the block rotation. EVALUATION: Formative evaluation of the program by residents was used to shape the program design. Residents' self-perceived competence in eight areas of community pediatrics was measured with questionnaires administered before and after completion of the rotation. Resident involvement in school consultation and child advocacy projects was assessed in a cross-sectional survey. RESULTS: Twenty-three residents completed the rotation during the 1-year study period. Statistically significant improvements in self-perceived competence were noted in all eight areas of community pediatrics. Among residents who were at least 3 months beyond the rotation completion date, 55% (11/20) reported continued involvement with their school consultation or child advocacy project, and 25% (5/20) reported this involvement to be on a quarterly to monthly basis. CONCLUSIONS: Two institutions successfully implemented and integrated a block rotation in community pediatrics. Positive short-term improvements were noted in resident self-perceived competence in community pediatrics.

Establishing a research agenda for school nursing.

During 1996, representatives from two professional organizations--American School Health Association and National Association of School Nurses--met collaboratively to identify and rank order key questions regarding contemporary research needs in school nursing services. This article summarizes existing literature and proposes areas for research. Recommendations are offered for nurses, school health program administrators, educators of school nurses, professional organizations, and others who plan and provide health care for school-aged youth.

Establishing a research agenda for school nursing.

During 1996, representatives from two professional organizations, the American School Health Association and the National Association of School Nurses, met collaboratively to identify and rank order key questions regarding contemporary research needs about school nursing services. This article summarizes existing literature and proposes areas for research. Recommendations are offered for nurses, school health program administrators, educators of school nurses, professional organizations, and others who plan and provide health care for children and school-aged youth.

The school of nurse as health educator.

Contrary to common opinion, the number of nurses who provide services in the nation's preschool, elementary, and secondary schools is not declining and currently is about 30,000. These members of school health teams can play a variety of roles that have a positive impact on patterns of health behaviors established during school years. Contributions that school nurses can make to school health instruction could include teaching individual clients, providing classroom instruction, being a member of curriculum planning committees, sharing resources with classroom teachers, and modeling health-promoting behavior. Although all school nurses should assume roles in health education, this article provides a framework to help nurses make decisions about which roles are appropriate in their practice setting, which tasks are within their area of expertise, and how health education fits into expectations of their employers. Specific roles in staff health promotion that use the unique experience, knowledge base, and skills of nurses are suggested, as well as ways that nurses can be advocates for comprehensive school health education. The article also poses four questions to assist nurses in evaluating their situation and their ability to be effective providers and advocates of health education in school.

Effect of adjuvant therapy on development of diabetes in mouse and man.

Freund's complete adjuvant (CFA) and BCG vaccine modulate the development of type 1 diabetes in animal models. In non-obese diabetic mice, CFA and BCG significantly reduced the proportion developing diabetes compared with controls. Histological examination showed that autoimmune disease still developed but had been diverted to become nondestructive. In a preliminary trial in 17 newly diagnosed, type 1 diabetic patients, intracutaneous administration of 0.1 mL of BCG 1 mg/mL led to clinical remission in 11 (65%)--by week 4 in 6. Remission has been sustained in 3 for 6-10 months. No side-effects were reported. A double-blind trial of BCG is warranted.

CD8 T cells are not required for islet destruction induced by a CD4+ islet-specific T-cell clone.

A panel of CD4+ T-cell clones has been isolated from the spleen and lymph nodes of diabetic NOD mice. These clones have been shown to be islet-specific both in vivo and in vitro. One of the clones, BDC-6.9, initiates extensive damage to islet tissue when placed adjacent to an NOD islet graft that has been used to reverse diabetes in (CBA x NOD)F1 recipients or when injected intraperitoneally into such animals. In this study, we show that BDC-6.9 T cells can initiate islet destruction in the absence of detectable CD8 T cells either in the periphery or in the lesion that develops after the transfer of the cloned islet-reactive T cells.

Family history fails to detect the majority of children with high capillary blood total cholesterol.

To examine the predictive value of family history in detecting children with high blood cholesterol, finger-stick screening was done in 1,118 children ages 9-10 whose parents provided parental and grandparental history of cardiovascular disease events and risk factors. Mean blood total cholesterol was 167.7 mg/dl with no significant gender or ethnic differences. Of 157 children with blood cholesterol 200 mg/dl or greater, only 61 (38.9%) had a family history of early myocardial infarction or hyperlipidemia; however, the prevalence of a positive family history varied from 2.8% in Vietnamese-Americans to 38.5% in Spanish-surnamed students to 52.6% in all other children. Adherence to current policies recommending screening only children with a positive family history will result in failing to detect a majority of children whose blood cholesterol levels exceed desirable levels for adults, particularly those from ethnic families recently arrived in the U.S.

In vivo activity of an islet-reactive T-cell clone.

BDC-6.9 is a CD4-positive T-cell clone, specific for NOD islets, which was isolated from the spleen and lymph nodes of a diabetic NOD mouse. The cells were transplanted in a blood clot adjacent to established NOD islet grafts in diabetic (CBA X NOD)F1 recipients. The BDC-6.9 cells initiated extensive damage to the islet grafts, while a non-islet specific clone transplanted adjacent to grafted islets caused no noticeable damage. In addition, the BDC-6.9 cells initiated similar destruction when injected intraperitoneally, suggesting that they may have some migratory capacity. By introducing these islet-reactive cells into the (CBA X NOD)F1, a non-diabetes prone environment, we hope to clarify the role of the islet-specific CD4 cell as related to islet destruction in vivo.

School-based blood cholesterol screening.

Coronary artery disease, the major cause of death in developed countries, begins early in childhood. Elevated blood cholesterol, a major risk for coronary artery disease in adults, has been associated at autopsy with atherosclerotic disease in children. To explore the feasibility of mass screening of blood cholesterol levels in children, a school-based screening and education program for fourth-graders was carried out in a Southern California school district. Approximately 10% of the children had blood cholesterol levels of 200 mg/dl or more, the upper limit of desirable levels for adults. These children and their parents returned for repeat cholesterol testing and nutrition counseling. A family history of early coronary artery disease was present in only one third of the children with high cholesterol levels; this fact, coupled with consumable costs less than $2 per child, suggests that cholesterol screening is a practical, cost-effective addition to school health programs.

Concentration of 3-methylindole (3MI) and distribution of radioactivity from 14C-3MI in goat tissues associated with acute pulmonary edema.

3-Methylindole (3MI) can cause acute pulmonary edema in goats. Because of known lipophilic properties and direct effects on biological membranes, the concentration of 3MI and distribution of radioactivity from 14C-3MI in tissues was investigated during development of 3MI-induced APE. Goats were given a 2 hr jugular infusion of 3MI containing 14C-3MI using propylene glycol as the vehicle. Groups of 3 goats were killed at 0, 5, 2 and 4 hr and 2 goats were killed at 8 and 24 hr. Plasma, lung, liver, kidney and other selected tissues were collected. 3MI was rapidly cleared from blood plasma and tissues after infusion, and 81% of the radioactivity was excreted in the urine by 24 hr. Maximum concentrations of unmetabolized 3MI in the tissues ranged from 2.6 to 15 micrograms 3MI/g, including 7.5 micrograms 3MI/g in the lung. The ratios of equivalent radioactivity to unmetabolized eMI indicated rapid metabolism and the presence of metabolites in all tissues studied. The lung contained the highest proportion of metabolites with ratios of radioactivity to unmetabolized 3MI of about 50, 10, 250, 150 and 80 at 0.5, 2, 4, 8 and 24 hr. The data demonstrate that 3MI does not selectively concentrate in the lung and that the concentrations are lower than those usually associated with direct membrane damage. They also indicate that 3MI is rapidly metabolized and that metabolites are present in tissues, especially the lung. These results suggest that direct effects of 3MI on biological membranes are not primarily responsible for lung injury in goats.

Ultrastructural pulmonary changes induced by intravenously administered 3-methylindole in goats.

Transmission electron microscopy was used to characterize early pulmonary lesions in goats after a 2-hour intravenous infusion of 0.04 g 3-methylindole (3MI) per kilogram body weight. Groups of 2 or 3 goats were euthanized at 0.5, 2, 4, 8, and 24 hours after the beginning of the infusion. Changes in lung ultrastructure were compared to noninfused and carrier-infused (propylene glycol) controls. By 0.5 hour, mitochondria and intracellular vesicles were swollen in capillary endothelial, alveolar, and nonciliated bronchiolar epithelial cells. Morphologic changes were most severe in the alveolar Type 1 and nonciliated bronchiolar epithelial cells. Interalveolar septums were swollen at 0.5 hour, and interstitial edema was severe at 2 hours. Denuded alveolar epithelial basement membranes were also observed at 2 hours, and some endothelial cells appeared dark and necrotic. Endothelial cells appeared normal after 2 hours. By 4 hours, the remaining intact alveolar Type 1 cells contained larger and more prominent clusters of smooth endoplasmic reticulum, compared with controls. Morphologic changes in alveolar Type 1 and nonciliated bronchiolar epithelial cells became progressively more severe during the 24-hour experiment. These findings demonstrate that 3MI induces a rapid cytotoxic effect primarily on alveolar Type 1 and nonciliated bronchiolar epithelial cells. Proliferation of smooth endoplasmic reticulum in these cells suggests involvement of the mixed function oxidase system in 3MI-induced pneumotoxicity.

Comparative studies on the cytotoxicity of amphibole and serpentine asbestos.

The chemical and physical properties of serpentine and amphibole asbestos are considered in the context of their interaction with tissue of the tracheobronchial tree and lungs. In vitro studies in cultures of several types are evaluated and work with the erythrocyte hemolysis system is reviewed. Although fibers of the two major mineral types differ substantially, it is likely they are modified by secretions and membranes of cells after inhalation to the respiratory tract. Investigations using virgin asbestos might not provide an accurate picture of events in vitro.

3-methylindole-induced pulmonary injury in goats.

Ruminal administration of 3-methylindole in goats severe pulmonary edema and respiratory distress. Electron microscopic studies of lungs reveal extensive degeneration and necrosis of alveolar membranous pneumocytes and bronchiolar epithelium. The necrosis of the pneumocytes is followed by proliferation of granular pneumocytes, which repopulate the alveolar basal lamina scaffold. 3-Methylindole may also induce proliferation of smooth endoplasmic reticulum in the remaining membranous pneumocytes and nonciliated columnar cells, indicating that these two cell types are involved in the xenobiotic function of the lung. The results suggest that 3-methylindole in cigarette smoke may play an important role in the pathogenesis of small airway disease and emphysema, and that patients with severe liver diseases or portocaval shunt may be predisposed to diffuse alveolar damage by 3-methylindole produced in the intestinal tract.

Induction of pulmonary edema and emphysema in goats by intraruminal administration of 3-methylindole.

The effects of intraruminal administration of 3-methylindole (3MI; skatole) were determined in goats. The 3MI was given to 4 goats at the dose level of 0.3 g/kg of body weight, to 2 goats at 0.2 g/kg, and to 2 goats at 0.1 g/kg; 3 nontreated goats were used as controls. Clinical signs of acute progressive respiratory tract disease were seen in all treated goats. Goats given the largest dose of 3MI (0.3 g/kg) died between 5 and 11 hours after treatment; those given smaller doses (0.2 and 0.1 g/kg) died between 79 and 92 hours. Increased plasma concentrations of 3MI were detected in goats give 0.1 or 0.2 g/kg within 3 hours after administration. By 24 and 36 hours, the concentrations of 3MI in the plasma decreased to low or nondetectable amounts and remained low for the duration of the experiment. Clinical signs of respiratory distress in the goats progressed after 3MI had been cleared from the plasma. Diffuse pulmonary edema and hydrothorax were extensive in goats which died early in the course of the experimentally induced disease. In goats which died at later stages, the lungs were firm and had less watery transudate. Temporal variations in the nature of pulmonic changes were even more obvious by microscopic examination. Diffuse pulmonary edema was the predominant early change. Small foci of emphysema were apparently caused by overdistention of some clusters of alveoli. Marked septal thickening and proliferation of alveolar cells were the prominent changes in goats which died between 79 and 92 hours after treatment. Incubation of L-tryptophan with caprine ruminal fluid resulted in formation of indoleacetic acid, indole, and 3MI. Similar incubations did not convert indoleacetic acid to 3MI. Control incubations showed 3MI as a fermentation metabolite, indicating it exists in caprine ruminal fluid in vivo. Results demonstrated that goats are susceptible to intraruminal administration of 3MI. The transitory appearance of 3MI in the plasma associated with progressive respiratory tract disease was similar to observations in cattle give 3MI. Clinical signs and lesions seen at necropsy were qualitatively similar to those reported in cattle given tryptophan and indoleacetic acid.