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Biomedical subjects

J S Allen

Publications and source records attributed to J S Allen.

At least 19 recordsLinked to original sources
PubMed1998

Patterns of prehistoric human mobility in polynesia indicated by mtDNA from the Pacific rat.

Human settlement of Polynesia was a major event in world prehistory. Despite the vastness of the distances covered, research suggests that prehistoric Polynesian populations maintained spheres of continuing interaction for at least some period of time in some regions. A low level of genetic variation in ancestral Polynesian populations, genetic admixture (both prehistoric and post-European contact), and severe population crashes resulting from introduction of European diseases make it difficult to trace prehistoric human mobility in the region by using only human genetic and morphological markers. We focus instead on an animal that accompanied the ancestral Polynesians on their voyages. DNA phylogenies derived from mitochondrial control-region sequences of Pacific rats (Rattus exulans) from east Polynesia are presented. A range of specific hypotheses regarding the degree of interaction within Polynesia are tested. These include the issues of multiple contacts between central east Polynesia and the geographically distinct archipelagos of New Zealand and Hawaii. Results are inconsistent with models of Pacific settlement involving substantial isolation after colonization and confirm the value of genetic studies on commensal species for elucidating the history of human settlement.

Animals↗
PubMed1998

Characterization of the eosinophil chemokine RANTES in nasal polyps.

Previous studies have demonstrated that the cytokine RANTES (Regulated And Normal T cell Expressed and Secreted) has been shown to be a potent mediator of eosinophil chemotaxis in vitro and of leukocyte recruitment. Because eosinophils are the hallmark cells in nasal polyposis, we hypothesize that RANTES is locally produced within the nasal polyp microenvironment and is responsible for the eosinophil recruitment seen in nasal polyposis. To begin to test this hypothesis, we evaluated nasal polyps from 17 patients and 3 control specimens for distribution and content of RANTES using immunohistochemical techniques and enzyme-linked immunosorbent assay technology. Our immunohistochemical studies demonstrated that in nasal polyposis, RANTES antigen staining occurred predominantly within eosinophils and epithelial cells. To quantify the relative levels of RANTES in normal and nasal polyp specimens, tissue homogenates were prepared, quantified, and normalized to protein levels. We detected RANTES in all 17 nasal polyp tissue homogenates (566 +/- 16 pg/mg total protein). The RANTES levels in nasal polyp homogenates were nearly 40-fold higher than the RANTES levels in normal tissue (15.7 +/- 28.2 pg/mg total protein). Thus, it appears that increased expression of RANTES by eosinophils and epithelial cells within the nasal polyp microenvironment promotes eosinophil recruitment and activation within nasal polyps. We hypothesize that RANTES induces increased recruitment and activation of eosinophils, presumably contributing to the increased tissue changes associated with nasal polyposis.

Adult↗
PubMed1997

Double mutagenesis of a positive charge cluster in the ligand-binding site of the ferric enterobactin receptor, FepA.

Siderophores and colicins enter bacterial cells through TonB-dependent outer membrane proteins. Using site-directed substitution mutagenesis, we studied ligand recognition by a prototypic Escherichia coli siderophore receptor, FepA, that binds the iron chelate ferric enterobactin and colicins B and D. These genetic experiments identified a common binding site for two of the three ligands, containing multiple positive charges, within cell surface residues of FepA. Elimination of single residues in this region did not impair the adsorption or transport of ferric enterobactin, but double mutagenesis in the charge cluster identified amino acids (Arg-286 and Arg-316) that participate in siderophore binding and function in FepA-mediated killing by colicins B and D. Ferric enterobactin binding, furthermore, prevented covalent modification of FepA within this domain by either a fluorescent probe or an arginine-specific reagent, corroborating the involvement of this site in ligand recognition. These results identify, for the first time, residues in a TonB-dependent outer membrane protein that participate in ligand binding. They also explain the competition between ferric enterobactin and the colicins on the bacterial cell surface: all three ligands interact with the same arginine residues within FepA during their penetration through the outer membrane.

Amino Acid Sequence↗
PubMed1997

Ancient DNA from Polynesian rats: extraction, amplification and sequence from single small bones.

The human colonisation of Polynesia was a major event in world prehistory. It represents one of the last human population migrations, and one which required crossing major water barriers. Though the subject of Pacific population origins has been approached by scholars from numerous fields for nearly a century, recent years have seen the problem addressed by human geneticists. Since the initial report describing the recovery of DNA from skeletal remains, ancient DNA studies have also focused on the Pacific region. In this paper we present the results of ancient DNA analyses of Rattus exulans, an animal that was transported by ancestral Polynesians through the Pacific to the far reaches of the Polynesian triangle. Analysis of DNA of R. exulans skeletal remains has many advantages over studies of ancient human remains, yet the one drawback has been the recovery of ancient DNA from single bones of these very small rodents. We have successfully modified standard extraction protocols for ancient DNA and have consistently extracted, amplified and sequenced mitochondrial DNA (mtDNA) from less than 0.1 g of R. exulans bone and tooth samples recovered from archaeological sites throughout the Pacific, ranging from 400 to 2000 years old.

Animals↗
PubMed1997

Interleukin-8 expression in human nasal polyps.

The cytokine interleukin 8 (IL-8) has been shown to be a potent mediator of leukocyte recruitment and neovascularization in inflammatory and neoplastic diseases. In this study we hypothesize that IL-8 produced in the nasal polyp microenvironment is responsible for the leukocyte recruitment seen in nasal polyposis. To test this hypothesis we evaluated nasal polyps for distribution and content of IL-8 antigen with immunohistochemical techniques and radioimmunoassay to determine tissue levels of IL-8. The immunohistochemical results demonstrated that IL-8 antigen staining occurred predominantly within inflammatory cells and epithelium. IL-8 was detected in all nasal polyp tissue homogenates (a mean value of 1767 +/- 1633 pg/mg total protein (TP) with a range of 134 to 3668 pg/mg TP vs control specimens with a mean value of 77 pg/mg TP with a range of 0.09 to 255 pg/mg TP). These data demonstrate the presence and distribution and levels of IL-8 antigen in nasal polyps in vivo, supporting our hypothesis that local production of IL-8 could be an important factor in the sustained recruitment of leukocytes in nasal polyposis. Thus IL-8 likely plays a significant role in the pathogenesis of this disease process and therefore is a potential target for therapeutic intervention.

Adult↗
PubMed1997

At issue: are traditional societies schizophrenogenic?

Schizophrenia is apparently less common in traditional than in nontraditional societies, and the course of illness in these cultural settings may also be more benign. Viral, political, economic, social labeling, and other explanations have been offered over the years for these differences. In contrast to those ideas that suggest the presence of a schizophrenogenic stress in urbanized, Westernized populations, I propose that traditional societies are actually schizophrenogenic compared with nontraditional societies. Assuming a multifactorial threshold model for the development of schizophrenia, traditional societies may be characterized by a lower threshold for developing schizophrenia in at-risk individuals. In the short term, this leads to a greater proportion of all clinical cases being of a less severe variety; in the long term, genes predisposing individuals to develop schizophrenia are exposed to the effects of negative selection, ultimately resulting in a relatively lower level of overt schizophrenia in these populations. The greater social demands placed on individual actors in traditional societies and the lack of variability in social network size may contribute to the (relatively) schizophrenogenic environment.

Cross-Cultural Comparison↗
PubMed1997

Smooth pursuit eye movements in schizophrenia in New Zealand.

OBJECTIVE: The objective of this study was to answer the following questions: what is the frequency of smooth pursuit dysfunction in schizophrenia in New Zealand; is it comparable to that observed in other populations; is it specific to schizophrenia; and is it represented in major ethnic groups present in New Zealand? METHOD: Patients with schizophrenia (n = 26) were recruited at five clinical facilities in the Auckland region. Diagnoses were taken from clinical records. Patients' smooth pursuit eye movements while following sinusoidal and triangular wave targets were recorded and their performance compared to a control population (n = 34). Eye movements were scored using the In(s/n), pursuit gain, and saccadic frequency measures. RESULTS: Patients with schizophrenia scored significantly worse than controls using the in(s/n) measure and had significantly higher saccadic frequencies for both targets. Percentile equivalents allow the estimation that about 50% of patients with schizophrenia have smooth pursuit dysfunction (SPD). There was no difference between groups for pursuit gain score, although low gain pursuit was significantly correlated with higher medication in the schizophrenia patient group. There were no differences associated with age, sex or ethnicity. The SPD marker was found in European- and Polynesian-derived New Zealanders. CONCLUSIONS: The results of the present study are consistent with results of previous studies performed elsewhere. Differences are at least partly ascribable to variations in methods. Smooth pursuit dysfunction is a robust marker for schizophrenia. Its application would be particularly useful in the New Zealand context as part of a first admission study looking at the effects of ethnicity on schizophrenia prognosis and on the stability of psychiatric diagnoses.

Adult↗
PubMed1996

Antisaccadic eye movements and attentional asymmetry in schizophrenia in three Pacific populations.

Antisaccadic eye movements were examined in 50 patients with schizophrenia and in 77 controls in three Pacific populations, namely New Zealand, Palau and Papua New Guinea. Despite the great biocultural variation encompassed by these three populations, schizophrenic patients made significantly more antisaccadic-errors than controls (36% vs. 13%), as has been demonstrated previously in other populations. This neurocognitive deficit may be consistent with frontal lobe dysfunction in schizophrenia. In addition, patients with schizophrenia made significantly more errors than expected when the target was presented in the right visual field (RVF). This trend was observed in patients from all three study areas, and was not seen in any of the control populations. Antisaccadic test performance in schizophrenia may be influenced by lateralized (left hemisphere) neuroanatomical impairment.

Adult↗
PubMed1995

Relation between backward masking deficits and smooth pursuit dysfunction in schizophrenia?

Backward masking deficit and smooth pursuit dysfunction are cognitive, information processing markers associated with schizophrenia. In schizophrenia, backward masking is typically manifest as a longer interstimulus interval over which a mask is still effective in interfering with the processing of a preceding target. Smooth pursuit dysfunction is characterized by saccadic smooth pursuit, saccadic intrusions, and low-gain pursuit. Although the natures of the two markers relative to schizophrenia are somewhat different (e.g., smooth pursuit dysfunction is a genetic marker; backward masking is associated more strongly with negative symptoms, poor prognosis schizophrenia), information processing theory indicates a possible neurocognitive relation between the two.

Eye Movements↗
PubMed1995

Eye movements and schizophrenia in Papua New Guinea: qualitative analyses with case histories.

Smooth pursuit eye movement dysfunction is a psychophysiological and genetic marker for schizophrenia seen in 50-80% of patients and in about 40% of their first-degree relatives. In this study, we qualitatively assessed the smooth pursuit eye movements of 33 psychiatric patients (including 32 diagnosed with schizophrenia) and 30 control subjects in the Port Moresby area of Papua New Guinea. Brief case histories of each patient were also reviewed. Using a conservative estimate of smooth pursuit dysfunction, we found that 42% of the psychiatric patients had the marker, compared to 10% of the controls. Specific eye movement abnormalities were also much more common among the patients. A patient who had previously 'run amok' and another who was a cargo cultist had smooth pursuit dysfunction; a patient whose psychotic symptoms may have been due to cerebral malaria did not have the marker. Highland and coastal patients were similar in their expression of the marker. This study, the first of its kind done outside of large-scale, urbanized societies, provides further evidence for a common biological basis for schizophrenia in biologically and culturally diverse populations worldwide.

Acute Disease↗
PubMed1994

A perfluorochemical emulsion for prehospital resuscitation of experimental hemorrhagic shock: a prospective, randomized, controlled study.

OBJECTIVE: To evaluate the efficacy of a novel, oxygen-transporting perfluorochemical emulsion as a prehospital therapy, using a canine hemorrhagic shock model based on compromised tissue oxygenation. DESIGN: Prospective, randomized, controlled study. SETTING: HemaGen animal laboratory. SUBJECTS: Sixteen healthy, adult male grade beagles (weight 8 to 14 kg). INTERVENTIONS: Administration of lactated Ringer's solution (n = 8), 15 mL/kg and perfluorochemical emulsion admixed with physiologic salts (n = 8), 15 mL/kg. MEASUREMENTS AND MAIN RESULTS: PaO2 increased significantly (p < .01) in the perfluorochemical-treated animals for 2 hrs after resuscitation. Mixed venous PO2 returned to preshock values in the perfluorochemical-treated dogs for 60 mins after fluid administration (p < .01). Normalization of hemodynamic variables was not observed in either group. Although not statistically significant, survival of the lactated Ringer's solution-treated animals was 63% compared with 100% for the perfluorochemical-treated dogs at 3 hrs after resuscitation. CONCLUSIONS: Resuscitation with a perfluorochemical emulsion augmented oxygen transport and restored global tissue oxygenation after massive hemorrhage, which translated into improved survival when compared with the group receiving an equal volume of lactated Ringer's solution.

Animals↗
PubMed1993

Computer analysis of eye movements.

An interactive program package for the acquisition, analysis and plotting of human eye movements is introduced. It is shown that the programs described in this paper can be used by scientists in a wide range of disciplines in spite of their different data analysis requirements. An example dealing with smooth pursuit tracking is given.

Eye Movements↗
PubMed1993

AIDS risk behaviors and knowledge among heterosexual alcoholics and non-injecting drug users.

The disinhibitory effects of abusable substances on sexual behavior and the increasing HIV prevalence among heterosexuals suggest that alcoholics and non-injection drug users may be at risk for HIV infection. We examined alcohol and non-injection drug use as AIDS risk factors, AIDS risk knowledge, and the effect of AIDS education upon voluntary HIV testing among 91 heterosexual male inpatients in a VA alcohol rehabilitation program. Questionnaire data revealed relationships between age, the use of alcohol, marijuana and intranasal cocaine just prior to sex and an increase in the number of female sexual partners. Use of alcohol just prior to sex was also associated with an increased number of unprotected sexual behaviors. AIDS risk knowledge in our sample was comparable to norms from previous studies. Inpatients received education concerning alcohol and sexuality either with or without an AIDS component. AIDS education and offer of HIV testing were associated with increased requests for HIV testing.

Acquired Immunodeficiency Syndrome↗
PubMed1991

DNA deaminating ability and genotoxicity of nitric oxide and its progenitors.

Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were greater than 99% C----T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer.

Codon↗