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Biomedical subjects

M B Roberts

Publications and source records attributed to M B Roberts.

At least 19 recordsLinked to original sources

Histomorphometric age assessment of the Boxgrove 1 tibial diaphysis.

Histomorphometric analysis of a medial midshaft chip from the Middle Pleistocene (ca. 500 ka BP) hominid tibia from Boxgrove, U.K. provides a modal age-at-death estimate at the end of the fourth decade of life. This makes Boxgrove 1 one of the older known and systematically aged Middle Pleistocene hominid specimens, and it reinforces the pattern of an underrepresentation of older adults observed in Middle and Late Pleistocene archaic Homo samples.

Age Determination by Skeleton↗

Diaphyseal cross-sectional geometry of the Boxgrove 1 Middle Pleistocene human tibia.

Cross-sectional geometric analysis of the early Middle Pleistocene human tibia from Boxgrove, West Sussex, U.K. reveals a mosaic pattern relative to other archaic Homo tibiae. The specimen has relatively low percent cortical area within its cross sections. However, it exhibits the high mediolateral strength characteristic of archaic Homo tibiae. Scaled solely to tibial length it is robust, similar to those of the Neandertals and above those of early modern and pre-Late Pleistocene African and Asian humans. However, given ecogeographically-patterned variance in relative tibial length and body laterality, it is most likely that it exhibits a level of robusticity within the range encompassed by Late Pliocene to Late Pleistocene archaic Homo combined with arctic body proportions. Given its association with late interglacial cool temperate climatic indicators, the inferred body proportions of the Boxgrove hominid were probably promoted by their minimal level of cultural buffering, requiring a significant biological conservation of body heat.

Animals↗

High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni.

In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.

Adolescent↗

The Middle Pleistocene human tibia from Boxgrove.

The Boxgrove tibia was discovered in 1993, associated with Middle Pleistocene fauna, and Lower Palaeolithic archaeology. The sediments at Boxgrove were deposited during a temperate interglacial episode and ensuing cold stage. They thus represent a wide range of modes and environments of deposition. Archaeological remains have been excavated from all the major stratigraphic units, giving a continuity of occupation for this part of southern England over a 10(4) year timescale, through markedly changing climatic regimes. The stratigraphic, archaeological and sedimentological contexts of the tibia are described, as well as its preservation and morphology. Measurements are given, with discussion of reconstructed bone length, and stature estimates. Comparative measurements are provided for fossil and recent human samples: the large dimensions of its diaphysis place the Boxgrove tibia near or beyond the upper size limits of the comparative samples, but its reconstructed length and estimated stature are less exceptional. The elevated robusticity of the specimen indicates exceptional diaphyseal strength and/or cold adapted body proportions paralleling those of the Neanderthals. Disagreement about the taxonomy of Middle Pleistocene hominids and lack of comparable fossil material make a specific assignment for the Boxgrove tibia problematic. The tibia can only definitely be assigned to non-modern Homo sp., with possible further reference to Homo cf. heidelbergensis (Schoetensack, 1908) on temporal and geographic grounds, if the validity of that species is accepted.

Animals↗

Efficacy of an individualized, motivationally-tailored physical activity intervention.

This study compared the efficacy of two low-cost interventions for physical activity adoption. Sedentary (N = 194) adults recruited through newspaper advertisements were randomized to receive either a motivationally-matched, individually-tailored intervention (IT) or a standard self-help intervention (ST). Assessments and interventions were delivered by repeated mailings at baseline, one, three, and six months. Participants were assessed regarding current physical activity behavior, motivational readiness to adopt regular physical activity, and psychological constructs associated with physical activity participation (e.g. self-efficacy, decisional balance). Repeated measures analyses of variance (ANOVAs) revealed significant increases in physical activity participation between baseline and six months for both groups with a significantly greater increase among IT participants. The IT group outperformed the ST group on all primary outcome measures: (a) minutes of physical activity per week, (b) reaching Centers for Disease Control and American College of Sports Medicine (CDC/ACSM) recommended minimum physical activity criteria, and (c) achieving the Action stage of motivational readiness for physical activity adoption. Both groups showed significant improvement between baseline and six months on the psychological constructs associated with physical activity adoption (e.g. self-efficacy), with no significant differences observed between the treatment groups. Utilizing computer expert systems and self-help manuals to provide individually-tailored, motivationally-matched interventions appears to be an effective, low-cost approach for enhancing physical activity participation in the community.

Adult↗

A hominid tibia from Middle Pleistocene sediments at Boxgrove, UK.

Fossil hominids from the earlier Middle Pleistocene of Europe are very rare and the Mauer mandible is generally accepted as the most ancient, with an estimated age of 500 kyr. We report here on the discovery of a human tibia, in association with stone tools, from calcareous silts at the Lower Palaeolithic site of Boxgrove, West Sussex, UK (Fig. 1). The silt units are correlated by mammalian biostratigraphy to an, as yet unnamed, major temperate stage or interglacial that immediately pre-dates the Anglian cold stage. Accordingly, the temperate sediments are equated with oxygen isotope stage 13 (ref. 6) and are therefore roughly coeval with the Mauer mandible. The massive tibia is the oldest hominid fragment from the British Isles and provides the first information about the manufacturers of the early Acheulian industries of Europe. It is assigned to Homo cf. heidelbergensis.

Animals↗

Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti-Ia antibodies: differential effects of anti-I-A vs. anti-I-E antibodies.

On a B10 genetic background noncure and cure phenotypes for murine visceral leishmaniasis are controlled by H-2. In this report results are presented which show the effects of administering specific anti-I-A and anti-I-E monoclonal antibodies to B10.D2/n (H-2d) noncure mice prior to and during 85 days of infection with Leishmania donovani LV9. The effects of the two anti-Ia antibodies were precisely equivalent in diminishing circulating anti-leishmanial IgG levels throughout infection, possibly as a direct effect of the anti-Ia antibodies in reducing the splenic B cell population. In terms of resolution of liver and spleen parasite loads, which is known to be dependent upon induction of a cell-mediated immune response, dramatically different results were obtained with the two anti-Ia antibodies. Anti-I-A treatment resulted in prolonged exacerbation of disease in liver and spleen. Anti-I-E treatment was associated with enhanced clearance of liver and spleen parasite loads beyond 30 days of infection. The results are consistent with the hypothesis that blocking major histocompatibility complex-restricted antigen presentation by one class II molecule allows T cell responses controlled by the other to predominate. Hence, in H-2d mice, I-E controls suppressor activity while I-A is associated with helper activity for cell-mediated control of infection. The results offer some prospect for the development of haplotype- and class II molecule-specific immunotherapeutic regimens in the host which might prevent the undesirable expansion of T cell populations which exacerbate disease without compromising development of a curative cell-mediated immune response.

Animals↗

Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum.

We have examined the relative roles of the macrophage (M phi) plasma membrane receptor for the cleaved third complement component (iC3b, CR3) and of the mannosyl/fucosyl receptor (MFR) in binding and ingestion of Leishmania donovani. In the absence of exogenous complement, the binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, were inhibited by the anti-CR3 monoclonal antibody M1/70, by the Fab portion of an anti-C3 antibody, or by the nucleophile, sodium salicyl hydroxamate, an inhibitor of C3 fixation. This provides strong evidence that M phi-derived, cleaved C3 (iC3b) present on the promastigote surface mediates binding to CR3. Equivalent inhibition of promastigote binding and ingestion was also observed using the soluble inhibitors of MFR activity, mannan or ribonuclease B. No additive effect for blocking the two M phi receptors simultaneously was observed. For amastigotes, which are poor activators of the alternative pathway, a lesser but nevertheless equivalent effect was observed for the three soluble inhibitors of CR3-mediated binding vs. the two soluble inhibitors of MFR-mediated binding. Modulation experiments in which either CR3 or MFR had been rendered inaccessible demonstrated that both receptors must be present on the segment of M phi membrane to which the parasite binds. The combined function of these two distinct M phi receptors may provide a general mechanism for recognition and ingestion of other pathogenic protozoa known to activate the alternative pathway.

Animals↗

An H-11-linked gene has a parallel effect on Leishmania major and L. donovani infections in mice.

The courses of visceral infection following intravenous injection of Leishmania donovani amastigotes, or lesion growth following subcutaneous injection of L. major promastigotes, were examined in B10.129(10M) (H-2b, H-11b) mice and compared with disease profiles observed in congenic C57BL/10ScSn(= B10) (H-2b, H-11a) and B10.D2/n (H-2d, H-11a) mice, and in BALB/mice. Possession of alternative alleles at H-11 and closely linked loci transformed the normal curing/healing phenotype of B10 mice into a characteristically different noncuring/nonhealing phenotype affecting both visceral and subcutaneous infections in B10.129(10M) mice. In reciprocal radiation bone marrow chimeras made between the congenic B10 and B10.129(10M) strains, both cure and noncure phenotypes were transferable with the donor hematopoietic system. Although it was possible to demonstrate transfer of suppression with T-enriched spleen cells from day 61 L. donovani-infected B10.129(10M) donor mice into 550 rad syngeneic recipients, the pretreatment of mice with sublethal irradiation did not, as in the earlier studies of Scl-controlled L. major nonhealing or H-2-controlled L. donovani noncure phenotypes, have a clear or consistent prophylactic effect. Together with the progressive disease profile observed even for L. donovani at low parasite doses this suggests that, despite their ability to develop initial delayed-type hypersensitivity reactions to parasite antigen early in L. major infection, B10.129(10M) mice possess some inherent defect in ability to mount a cell-mediated response effective at the level of macrophage antileishmanial activity in vivo even when suppressor T cells are not generated. Further elucidation of this characteristically different noncuring/nonhealing phenotype may provide important insight into common events involved in the development of the cell-mediated immune response to both visceral and subcutaneous forms of leishmaniasis.

Animals↗

A study of the differential respiratory burst activity elicited by promastigotes and amastigotes of Leishmania donovani in murine resident peritoneal macrophages.

Acridine orange and ethidium bromide and a combination of fluorescent and transmitted light microscopy used in conjunction with the qualitative nitroblue tetrazolium assay for superoxide anion (O2-) release demonstrated dramatic differences in the binding of and respiratory burst (RB) activity elicited by promastigotes and amastigotes of Leishmania donovani in resident peritoneal macrophages (M phi) from C57BL/10ScSn mice. When amastigotes were incubated with M phi for 30 min the number of parasites per 100 M phi was 2-4-fold higher, a higher proportion of M phi became infected and the mean number of parasites per infected M phi was higher than in promastigote infections. RB activity was higher for promastigotes than amastigotes both in terms of the percentage of infected M phi containing formazan positive parasites and the percentage of individual formazan positive parasites. In an attempt to explain the differential response to promastigotes and amastigotes, RB activity was examined for sodium azide-treated, glutaraldehyde-fixed and heat-killed parasites and for various transformation intermediates between amastigotes and promastigotes. Binding and RB activity were also examined in conjunction with competitive binding assays designed to determine the specific receptors involved in ligand binding of both forms of the parasite to the M phi. The results indicate that, while amastigotes may possess an azide-sensitive mechanism which either competes for O2- produced or causes localized inactivation of RB activity, this cannot account for the full magnitude of the difference between the two forms of the parasite. The transformation and competitive binding studies suggest that the more likely explanation lies in both qualitative and quantitative differences in the distribution of surface ligands involved in binding the parasite to the M phi plasma membrane and that the well characterized mannose/fucose receptor may be important in promastigote, but not amastigote, binding and RB activity.

Animals↗

The effect of aspirin and paracetamol on the increased naloxone potency induced by morphine pretreatment.

Using the abdominal constriction test in mice, it was shown that pretreatment with a single dose of morphine given 3 h previously caused a marked increase in the antagonistic effect of naloxone without any change in the antinociceptive action of morphine itself. Pretreatment with either paracetamol (10.0-20.0 mg/kg, s.c.) or aspirin (5.0-10.0 mg/kg, s.c.) caused a small but significant antagonism of the antinociceptive effect of morphine, while the antagonistic action of naloxone remained unaffected. However, when aspirin or paracetamol was administered with morphine in the pretreatment regime, the ability of morphine to induce an increase in naloxone potency was much attenuated. This inhibitory effect was dependent on the dose of aspirin or paracetamol used in the pretreatment regime. The antinociceptive effect of aspirin and paracetamol was also studied. In the doses used, they did have a mild antinociceptive effect, but the analgesic effect of morphine was not affected by the administration of these drugs 30 min beforehand. It is suggested that the antinociceptive effect of morphine is probably not dependent on prostaglandin, but that the induction of increased naloxone potency is likely to be mediated through prostaglandin synthesis.

Acetaminophen↗

Effect of morphine and naloxone on intestinal transit in mice.

Morphine caused a dose-dependent slowing of the rate of intestinal transit in mice. This inhibitory effect of morphine was antagonised by naloxone administration. Pretreatment with a single dose of morphine did not induce any detectable tolerance to the inhibitory effect of a second dose of morphine given 5 h later. However, naloxone was more effective in antagonising this inhibitory effect of morphine in morphine-pretreated mice than in saline-pretreated animals. Molecular sieve morphine pellet implantation for 24 h induced detectable tolerance to the inhibitory effect of morphine administered 3 h after removal of the pellet. In addition, the antagonistic effect of naloxone was also augmented when compared with blank pellet-implanted control animals. The present study has shown that the enhanced naloxone potency against the inhibitory effect of morphine was intestinal transit was observalbe before the development of overt tolerance, and that tolerance to the effect of morphine on the small intestine could be induced by implantation of a molecular sieve morphine pellet for 24 h.

Animals↗

The effect of phenobarbitone pretreatment on the narcotic antagonistic potency of naloxone in mice.

Pretreatment with phenobarbitone (5.0-20.0 mg/kg, s.c.) did not alter the antinociceptive effect (tail-flick assay) of morphine measured 4.5 h later. However, naloxone was more potent in antagonising this antinociceptive effect in phenobarbitone-pretreated mice than in saline-retreated animals. Concomitant administration of naloxone in the pretreatment regime did not alter the effect of phenobarbitone. The enhanced naloxone potency was related to the amount of phenobarbitone given, and was observable at 3.0 and 4.5 h after pretreatment. It was no longer apparent at 6.0 h. Because of a difference in time course and in the ability of naloxone to block the phenomenon, it is suggested that the mechanisms underlying the increase in naloxone potency induced by phenobarbitone pretreatment and morphine pretreatment may not be the same.

Analgesics↗

The effects of 4-imidazolyl-3-amino-2-butanone (McN-A-1293), a specific histidine decarboxylase inhibitor, on the expression of morphine tolerance and physical dependence in mice.

McN-A-1293, a specific histidine decarboxylase inhibitor administered intracisternally in the 'withdrawal' phase, significantly suppressed the expression of morphine tolerance. Severity of withdrawal, assessed by percentage body weight loss, was significantly enhanced although incidence of jumping was unaltered. The opposite effects of this compound on morphine tolerance and withdrawal suggest that tolerance and physical dependence are based on different underlying mechanisms.

Animals↗

The effects of D-histiding on the expression of morphine tolerance and physical dependence in mice.

D-Histidine, administered in the 'wthdrawal' phase of morphine addiction, failed to modify the expression of tolerance and physical dependence in mice. L-Histidine, on the contrary, can enhance tolerance and inhibit physical dependence. Whole brain histamine is markedly increased by L-histidine administration, but only minimally by D-histidine. This confirms that the actions of L-histidine on morphine addiction are stereospecific, and so can be more confidently correlated with the increase in brain histamine levels produced by the natural amino acid precursor.

Animals↗