Prince Edward Island Heart Health Dissemination Research Project: establishing a sustainable community mobilization initiative.

This paper provides an overview of the Prince Edward Island Heart Health Program (PEIHHP) Dissemination Research Project. Prince Edward Island (PEI) is a small province in the Atlantic region of Canada with a population of 137,980. The Island's economy is dependent on the fishery, agriculture, and tourism industries. Although unemployment rates are high (14.4%), Prince Edward Island has the lowest poverty rate in the country at 15.2%, high levels of social support (86%), and the second lowest rate of high chronic stress (Report on the Health of Canadians, 1996, 1999).

Evolution of endogenous retrovirus-like elements of the woolly mammoth (Mammuthus primigenius) and its relatives.

Endogenous retrovirus-like elements characterizable by a leucine tRNA primer (ERV-Ls) are reiterated genomic sequences known to be widespread in mammals, including humans. They may have arisen from an ancestral foamy virus-like element by successful germ line infection followed by copy number expansion. However, among mammals, only primates and rodents have thus far exhibited high copy number amplification and sequence diversification. Conventionally, empirical studies of proviral amplification and diversification have been limited to extant species, but taxa having good Quaternary fossil records could potentially be investigated using the techniques of "ancient" DNA research. To examine evolutionary parameters of ERV-Ls across both time and taxa, we characterized this proviral class in the extinct woolly mammoth (Mammuthus primigenius) and living elephants, as well as extant members of the larger clade to which they belong (Uranotheria, a group containing proboscideans, sirenians, hyraxes, and their extinct relatives). Ungulates and carnivores previously analyzed demonstrated low copy numbers of ERV-L sequences, and thus it was expected that uranotheres should as well. Here, we show that all uranothere taxa exhibit unexpectedly numerous and diverse ERV-L sequence complements, indicating active expansion within this group of lineages. Selection is the most parsimonious explanation for observed differences in ERV-L distribution and frequency, with relative success being reflected in the persistence of certain elements over a variety of sampled time depths (as can be observed by comparing sequences from fossil and extant elephantid samples).

Skull of Early Eocene Cantius abditus (Primates:Adapiformes) and its phylogenetic implications, with a reevaluation of "Hesperolemur" actius.

A substantially complete skull and mandible of the primitive adapiform Cantius is reported from the Early Eocene Willwood Formation of Wyoming. The mandible contains an almost complete lower dentition in which the lower incisors are strongly inclined and have spatulate crowns, I(2) is larger than I(1), and the canine is large and projecting. The cranium shares many features with those of Notharctus and Smilodectes but differs in having nasals that broaden proximally. Presence of a prominent canine and strong sagittal crest may indicate that it represents a male. The basicranium preserves auditory structures almost identical to those in extant noncheirogaleid lemurs, including a large bony tube for the stapedial artery and a small, open sulcus for the distal portion of the promontorial artery. The dentition is sufficiently primitive to be compatible with a relationship to either strepsirrhines or anthropoids, but the anatomy of the auditory region is more consistent with either specific relationship to lemurs or, more likely, a basal position that approximates the euprimate morphotype. Certain features of the basicranium of "Hesperolemur" actius, described by Gunnell ([1995] Am. J. Phys. Anthropol. 98:447-470) as being unlike that of any other adapiform, were either misinterpreted or are apparently no longer present in the holotype. Reassessment of these and other features indicates that in fact "H." actius differs little from Cantius and should not be separated from the latter at the genus level, although on dental grounds the species appears to be distinct (as C. actius).

The quaternary cuban platyrrhine Paralouatta varonai and the origin of Antillean monkeys.

We describe recently recovered dental and mandibular remains of the Cuban platyrrhine Paralouatta varonai, previously known from the holotype only (a nearly complete skull with very worn teeth). We also expand on the original description of the type specimen. Paralouatta is one of three extinct taxa of Greater Antillean Quaternary monkeys known from craniodental remains. The other two, Xenothrix mcgregori and Antillothrix bernensis, occurred in Jamaica and Hispaniola, respectively. It has been common practice to assume that Antillean monkeys were more closely related to individual mainland taxa than to each other. Thus, P. varonai was thought to be related to Alouatta; Antillothrix bernensis to Saimiri or Cebus; and X. mcgregori to Callicebus, or to callitrichines, or even to be of unknown affinity. With the discovery of well-preserved dental remains of Paralouatta, it can now be ascertained that this species was in fact very different from Alouatta. Cladistic analysis reveals a sister-group relationship between Antillothrix and Paralouatta, followed on the cladogram by Xenothrix and Callicebus (last taxon being the closest mainlaind relative of the Antillean clade). This conclusion has an important biogeographic implication: recognition of an Antillean clade, as advocated here, assumes only one primate colonization from the South American mainland, not several as previously believed.

T cell receptor (TCR) BV gene repertoires and clonal expansions of CD4 cells in patients with HIV infections.

Despite extensive investigation, the pathogenesis of T cell depletions that characterize AIDS has not been elucidated. To study this process further, we evaluated T cell antigen receptor beta-chain variable gene (TCRBV) repertoires in peripheral blood lymphocytes (PBL) of 23 HIV-infected patients. Expression levels of 28 TCRBV were determined by multiprobe RNase protection assay after polymerase chain reaction (PCR) amplifications. Abnormal expansions (> 2 s.d. from mean normal values) were frequent in HIV CD4, accounting for 26% of total measured TCRBV in this population. The number and magnitude of abnormalities among individuals were inversely proportional to their CD4 counts (P < 0.012 and P < 0.01, respectively). While abnormalities were not randomly distributed among TCRBV subfamilies, no particular genes were expanded or contracted among all patients. Only 14% of CD8 TCRBV were proportionally expanded (P < 0.01 compared with CD4), and there were limited concordances between paired CD8 and CD4 repertoires among individuals. CDR3 length analyses and TCRBV sequencing showed that most CD4 expansions comprised clonal or oligoclonal populations. Thus, T cell responses in HIV patients are characterized by severe TCRBV biases and clonal expansions among CD4 subsets, and these processes are exaggerated with disease progression. The heterogeneity and oligoclonality of the TCRBV expansions are consistent with responses to HIV-encoded or other conventional antigens rather than superantigenic effects. The presence of CD4 clonal proliferations in these patients may be important in the pathogenesis of HIV, and the absence or reduction of many T cell specificities due to oligoclonal expansions may increase susceptibility to opportunistic infections.

Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA.

The detection of a fatal case of reactivation of hepatitis B, in a previously vaccinated Indonesian patient after withdrawal of chemotherapy for lymphoma, was delayed because HBsAg was negative in a widely used monoclonal-antibody-based ELISA. The serum was later found to be strongly reactive for HBsAg by the polyclonal radioimmunoassay and for HBV DNA. PCR sequencing revealed a substitution of arginine for glycine at position 145 of HBsAg in the major neutralising epitope cluster, the a determinant, as well as a 2-aminoacid insertion of asparagine and threonine between positions 122 and 123, immediately upstream of this determinant.

Erythropoietin levels in cobalamin deficiency: comparison of anemic and non-anemic, subtly deficient patients.

The major stimulus for erythropoietin secretion is the circulating hemoglobin level, but other poorly understood factors appear to influence the erythropoietin level as well. Therefore, the effect of cobalamin deficiency was studied in patients who were not anemic, even though many of them had macrocytosis or metabolic deficiency of the bone marrow cells. All 15 cobalamin-deficient patients without anemia had normal erythropoietin levels, including the 4 patients with macrocytosis and 3 in whom metabolic cobalamin deficiency of the marrow cells was documented with the deoxyuridine suppression test. Moreover, among 21 cobalamin-deficient patients with anemia, the 4 least anemic patients also had normal erythropoietin levels. The other 17 anemic patients had elevated erythropoietin levels. Erythropoietin levels correlated with the severity of the anemia (r = 0.423, p less than 0.05). However, wide individual variations were observed; 4 patients with hemoglobin levels of 37-43 g/l had erythropoietin levels ranging from 69 to 3300 units/l, for example. These observations support the hypothesis that the hemoglobin level is the major, but not the sole factor that determines erythropoietin levels. As long as it does not produce anemia, however, cobalamin deficiency does not raise erythropoietin levels even when it induces metabolic deficiency of the bone marrow and macrocytosis.

Modified subfossil aye-aye incisors from southwestern Madagascar: species allocation and paleoecological significance.

Two of the three drilled aye-aye incisors collected in 1901 by Grandidier at the subfossil site of Lamboharana were recently rediscovered in uncatalogued collections of the Institut de Paléontologie in Paris. These teeth are not much wider or thicker than those of the extant aye-aye (Daubentonia madagascariensis), but their arc of curvature is noticeably greater. These facts indicate that the teeth probably belong to D. robusta, a large extinct aye-aye whose dentition is otherwise unknown. No other remains referable to Daubentonia have been reported from Lamboharana, although D. robusta is known from other localities in the southwest. The presence of Daubentonia in southern Madagascar does not demonstrate that this region was markedly more humid or densely forested in the recent past. It remains to be established whether the extinction of D. robusta throughout its range in southern Madagascar, and local disappearance of D. madagascariensis everywhere but in the eastern forest biotope, is due to late Holocene climatic change, to anthropogenic effects, or both factors combined.

Use of plasma somatomedin-C/insulin-like growth factor I measurements to monitor the response to nutritional repletion in malnourished patients.

Changes in plasma somatomedia-C/insulin-like growth factor I (Sm-C/IGF-I) concentrations are a sensitive indicator of the anabolic response of normal human volunteers to alterations in nutritional intake. To determine if measurement of this peptide could be used to monitor the response to nutritional repletion in malnourished patients, six patients were studied while receiving nutritional support for periods of 10-16 days. Plasma Sm-C/IGF-I increased from a mean basal level of 0.67 +/- 0.15 U/ml (+/-1 SD) to a peak of 1.80 +/- 0.44 U/ml on day 10, then declined to a concentration of 1.28 +/- 0.49 U/ml by day 16. All patients entered positive nitrogen balance by day 2 and nitrogen accretion continued throughout the study. Changes in serum concentrations of prealbumin, transferrin, and retinol-binding protein were compared to changes in Sm-C/IGF-I during nutritional support. Prealbumin increased to a posttreatment mean of 121 +/- 23% of control by the end of the study (p greater than 0.05, NS). Likewise, there was minimal change in retinol-binding protein, a peak value of 118 +/- 21% of control being reached by day 12 of treatment (p greater than 0.05, NS). Transferrin also showed minimal change, increasing to a mean value of 110% +/- 13% of control by day 12 (p greater than 0.05, NS). Measurement of plasma Sm-C/IGF-I concentrations appears to be a much more sensitive index of acute directional changes in nutritional status than other plasma proteins commonly used to monitor nutritional responses. The increase of Sm-C/IGF-I correlated temporally with entry into positive nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)

New Palaeogene primate basicrania and the definition of the order Primates.

The anatomy of the posterior basicranium has been repeatedly invoked in systematic definitions of Primates. One widely cited definition of the order claims that 'all undoubted primates' are distinguished from other mammals by two basicranial specializations: (1) absence of a major vascular foramen on the medial side of the auditory region, and (2) development of the auditory bulla from the petrosal bone. As we show here, specialization (1) does not apply to the paromomyid Ignacius, and is of uncertain incidence in other unquestioned members of suborder Plesiadapiformes (archaic primates from the early Cenozoic of Europe and North America). Specialization (2) cannot be demonstrated without ontogenetic evidence, and all relevant plesiadapiform fossils are adult. In fact, the only plesiadapiform with an arterial pattern remotely resembling that of early primates of modern aspect (or 'euprimates') is the microsyopid Cynodontomys, but it is often regarded as non-primate because it lacks a petrosal bulla. Although plesiadapiforms resemble euprimates in traits of the cheek teeth and postcranium, some other (presumably non-primate) groups possess these traits as well. Since the order Primates is not clearly definable by unique specializations, the best grounds for regarding plesiadapiforms as euprimate antecedents are stratigraphic and phenetic. This fact may be best expressed by systematic arrangements that emphasize adaptive grades rather than unsubstantiated clades.

A new fossil cebine from Hispaniola.

An incomplete mandibular fragment of a cebine monkey from an early Holocene Haitian cave deposit adds to the small but growing list of fossil Antillean primates. The jaw is of the correct size to belong to the same taxon as the partial maxilla of "Saimiri" bernensis from the Dominican Republic. Both finds probably represent a single species whose proximate ancestry lay closer to Cebus than to Saimiri, although more evidence will be required to substantiate this. No close relationship of the Hispaniolan fossils to the Jamaican platyrrhine Xenothrix is indicated. How monkeys managed to penetrate the West Indies is a biogeographical puzzle of the first order. Geographical vicariance events, island-hopping, and purposeful or inadvertent introduction by humans seem rather implausible devices. On the whole, long-distance, over-water rafting from the Americas remains the most likely mechanism for past land vertebrate immigration into the Caribbean.

Cryorenin in the newborn human and lamb.

Renin and big renin (cryorenin) were measured in the plasma of 78 babies at birth, and studied in six newborn lambs 2-3 weeks of age in response to angiotensin II (0.25 microgram/kg per min) infusion. There were (mean +/- S.E.M.) 15.9 +/- 2.0 ng/ml per h of renin and 11.1 +/- 2.3 of cryorenin, measured as plasma renin activity (PRA) in newborn cord blood. Cryorenin and renin decreased in parallel in the newborn lamb from 19 +/- 2.3 ng/ml per h and 28.6 +/- 2.7 to 6.5 +/- 1.8 (P less than 0.001) and 15.9 +/- 1.8 (P less than 0.01), respectively after 30 min of the angiotensin II infusion. Mean aortic blood pressure increased 30 mm Hg. These data suggest that cryorenin levels are high in the newborn lamb and human, and that both cryorenin and renin are under angiotensin II control in the newborn lamb.

Entotympanics, ontogeny and primates.

Ontogenetic investigations confirm that independent entotympanics are absent in living primates. Although cartilage occurs in the petrosal tympanic processes of some primates, the assumption that a suppressed entotympanic is thereby indicated can be adequately refuted according to embryological canons of interpretation. Problems regarding the homologies of different entotympanics, largely ignored by paleontologists and systematists, reduce or negate their taxonomic valency for all but closely related groups. Until such puzzles are resolved, the possible but doubtful existence of entotympanics in plesiadapoids and inferred pre-primate ancestors cannot buttress claims for alleged ties between primates and certain entotympanic-bearing eutherians (principally bats, colugos and tree shrews).

Ontogeny of the ectotympanic-petrosal plate relationship in strepsirhine prosimians.

The two major groups of living strepsirhine prosimians (the lorises and lemurs) display two different forms of the ectotympanic-petrosal plate relationship (EPPR). Ontogenetically, the factors producing this difference primarily relate to (1) the degree of elaboration of the sutural tissues at the ectotympanic-petrosal plate interface and (2) the method of pneumatization of the petrosal bone. These two processes are, in all likelihood, the same ones which determined the EPPRs fossil strepsirhines as well. The important theoretical point which emerges is that the transition from the intrabullar to the extrabullar condition of the ectotympanic (or vice versa) was probably effected partly or wholly in young rather than adults stages of ancestral strepsirhines.