Many adaptive explanations for anthropoid origins incorporate hypotheses regarding the function of the postorbital septum. Two hypotheses are evaluated here: Cachel's ([1979b] Am. J. Phys. Anthropol. 50:1-18) hypothesis that the anthropoid postorbital septum evolved to augment muscle attachment area in the anterior temporal fossa and Cartmill's ([1980] in RL Ciochon and AB Chiarelli (eds.): Evolutionary Biology of the New World Monkeys and Continental Drift. New York: Plenum, pp. 243-274.) hypothesis that the septum evolved to insulate the foveate eye of haplorhines from movements in the temporal fossa during mastication. Dissections of the masticatory muscles of 55 species of primates, with emphasis on the anatomy of the anterior temporal fossa, reveal that in all anthropoids the temporal muscles take origin from the portion of the septum formed by the frontal bone. In some platyrrhines this muscle is anterior temporalis, and in others it is zygomatico-mandibularis. In tarsiers and most platyrrhines, muscle attachment to the zygomatic portion of the postorbital septum is very restricted (and of possibly varying homologies), whereas in catarrhines the zygomatico-mandibularis arises from the postorbital ridge on the zygomatic portion of the septum. This suggests that, contrary to Cachel's hypothesis, the earliest anthropoids did not have extensive areas of muscle attachment on the postorbital septum, a suggestion supported by the bony morphology of Catopithecus browni. Dissections also indicate that in all haplorhines the anteriormost temporal fibers curve around the postorbital septum between origin and insertion, implying that, were the septum not present, the anterior temporal muscles would disturb the orbital contents when contracting. This suggests that insulation may have been the septum's original function, even in the absence of a retinal fovea. In anthropoids, the rostral migration of the line of action of the anterior temporal muscles relative to the eye is attributed to their possession of extreme degrees of both orbital frontation and convergence; in tarsiers it is attributed to their possession of both massively hypertrophied eyes and moderately convergent and frontated orbits. It is argued that the postorbital septum is most likely to have evolved in a morphological context similar to that exhibited by omomyids.

Animals↗

PubMed1995

Basicranial flexion, relative brain size, and facial kyphosis in Homo sapiens and some fossil hominids.

Comparative work among nonhominid primates has demonstrated that the basicranium becomes more flexed with increasing brain size relative to basicranial length and as the upper and lower face become more ventrally deflected (Ross and Ravosa [1993] Am. J. Phys. Anthropol. 91:305-324). In order to determine whether modern humans and fossil hominids follow these trends, the cranial base angle (measure of basicranial flexion), angle of facial kyphosis, and angle of orbital axis orientation were measured from computed tomography (CT) scans of fossil hominids (Sts 5, MLD 37/38, OH9, Kabwe) and lateral radiographs of 99 extant humans. Brain size relative to basicranial length was calculated from measures of neurocranial volume and basicranial length taken from original skulls, radiographs, CT scans, and the literature. Results of bivariate correlation analyses revealed that among modern humans basicranial flexion and brain size/basicranial length are not significantly correlated, nor are the angles of orbital axis orientation and facial kyphosis. However, basicranial flexion and orbit orientation are significantly positively correlated among the humans sampled, as are basicranial flexion and the angle of facial kyphosis. Relative to the comparative sample from Ross and Ravosa (1993), all hominids have more flexed basicrania than other primates: Archaic Homo sapiens, Homo erectus, and Australopithecus africanus do not differ significantly from Modern Homo sapiens in their degree of basicranial flexion, although they differ widely in their relative brain size. Comparison of the hominid values with those predicted by the nonhominid reduced major-axis equations reveal that, for their brain size/basicranial length, Archaic and Modern Homo sapiens have less flexed basicrania than predicted. H. erectus and A. africanus have the degree of basicranial flexion predicted by the nonhominid reduced major-axis equation. Modern humans have more ventrally deflected orbits than all other primates and, for their degree of basicranial flexion, have more ventrally deflected orbits than predicted by the regression equations for hominoids. All hominoids have more ventrally deflected orbital axes relative to their palate orientation than other primates. It is argued that hominids do not strictly obey the trend for basicranial flexion to increase with increasing relative brain size because of constraints on the amount of flexion that do not allow it to decrease much below 90 degrees. Therefore, if basicranial flexion is a mechanism for accommodating an expanding brain among non-hominid primates, other mechanisms must be at work among hominids.

Animals↗

PubMed1995

Cytokines and autoantibodies to cytokines.

Cytokines are essential components of our defense and repair systems but also potentially harmful mediators of infectious and immunoinflammatory reactions. Clinically important cytokines function systemically as pleiotropic hormones with overlapping effects on many cell types. All engage in a complex network of agonists and antagonists. Some immunoglobulin G (IgG) antibodies have been found to be potent and specific regulators of cytokines. These antibodies bind interleukin (IL-1)alpha, IL-6, IL-10, leukemia inhibitory factor (LIF), and interferon (IFN)-alpha/beta with exceptional force. They neutralize their corresponding cytokines ex vivo and perhaps in vivo, although they may also function as cytokine carriers. The biological role of autoantibodies to cytokines is not yet understood, but they may provide a level of regulation not appreciated at present. Inappropriate production/function of such antibodies could be pathogenetically involved in immunoinflammatory and other diseases. Cytokine antibodies may also contribute to the anti-inflammatory effects of human IgG therapy.

Adjuvants, Immunologic↗

PubMed1995

Cimetidine as an adjuvant treatment in colorectal cancer. A double-blind, randomized pilot study.

PURPOSE: To evaluate the influence of a H2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark. METHODS: A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate. RESULTS: In patients operated with curative intent (n = 148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P = 0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient category to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.

Adenocarcinoma↗

PubMed1995

High resolution structures of HIV-1 RT from four RT-inhibitor complexes.

We have determined the structures of four complexes of HIV-1 reverse transcriptase with non-nucleoside inhibitors, three fully refined at high resolution. The highest resolution structure is of the RT-nevirapine complex which has an R-factor of 0.186 and a root-mean-square bond length deviation of 0.015 A for all data to 2.2 A. The structures reveal a common mode of binding for these chemically diverse compounds. The common features of binding are largely hydrophobic interactions and arise from induced shape complementarity achieved by conformational rearrangement of the enzyme and conformational/configurational rearrangement of the compounds.

Amino Acid Sequence↗

PubMed1995

Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors.

The structure of unliganded HIV-1 reverse transcriptase has been determined at 2.35 A resolution and refined to an R-factor of 0.219 (for all data) with good stereochemistry. The unliganded structure was produced by soaking out a weak binding non-nucleoside inhibitor, HEPT, from pregrown crystals. Comparison with the structures of four different RT and non-nucleoside inhibitor complexes reveals that only minor domain rearrangements occur, but there is a significant repositioning of a three-stranded beta-sheet in the p66 subunit (containing the catalytic aspartic acid residues 110, 185 and 186) with respect to the rest of the polymerase site. This suggests that NNIs inhibit RT by locking the polymerase active site in an inactive conformation, reminiscent of the conformation observed in the inactive p51 subunit.

Antiviral Agents↗

PubMed1995

Immunohistochemical characterization of the cutaneous cellular infiltrate in different areas of chronic leg ulcers.

Current understanding of the immunological mechanisms involved in the pathogenesis of venous leg ulcers is insufficient. In this study the cellular composition of skin biopsies taken from the center, the edge, and 2 cm distant from the edge of venous leg ulcers was characterized quantitatively by immunohistochemical staining. In the epidermis the mean numbers of Langerhans cells (CD1a+) were four times lower at the edge of the ulcer compared to clinically intact epidermis 2 cm distant from the edge. In the dermis a statistically significant increase in the mean numbers of macrophages (CD68+) and neutrophils (NP57+) from the distant area towards the center of the ulcer was observed. No significant differences were observed in the distribution of T cells nor in the ratio of CD4+/CD8+ T-cell subsets between the different regions of the ulcer. About 30% of T lymphocytes were CD8+ in all microenvironments. The center and the edge of the ulcer were dominated by macrophages comprising 63% and 53% of the cells respectively, while T lymphocytes dominated the distant area. The area 2 cm distant from the edge was also heavily infiltrated by macrophages and neutrophils. B cells (CD22+) and NK cells (CD56+) were relatively rare in all areas, comprising less than 3% of the dermal infiltrate. In conclusion, local microenvironments each with a different cellular composition can be defined within venous leg ulcers.

Adult↗

PubMed1995

High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG.

This paper demonstrates and characterizes naturally occurring antibodies to interferon (IFN) in human IgG preparations. In vitro neutralization of the antiviral effect of IFN alpha and IFN beta, but not IFN gamma, was observed in 12 of 15 normal IgG preparations. The neutralizing capacity was higher against rIFN alpha 2A and rIFN alpha 2C than against lymphoblastoid IFN alpha and IFN beta. Frühsommer meningoencephalitis hyperimmune IgG and hepatitis-B hyperimmune IgG showed potent neutralization, whereas anti-rhesus D-, anti-rabies-, and anti-tetanus IgG showed weak neutralization. Saturable binding of 125I-rIFN alpha 2A was demonstrated only in those IgG preparations found to neutralize the antiviral effect of IFN. Significant correlation between IFN binding and neutralization capacity was observed. The antibodies bound with Fab to rIFN alpha 2A with an avidity of approximately 30 pM; the majority was of the IgG1 subclass. Maximum binding capacity was 490 pg rIFN alpha 2A/mg IgG. Cross-binding of rIFN alpha 2C, lyIFN alpha N1 and IFN beta occurred with 10 and 100-200 times lower activities than that of rIFN alpha 2A. There was no cross-binding with rIFN gamma or rIL-6. IgG preparations containing anti-IFN antibodies blocked the binding of 125I-rIFN alpha 2A to A549 cells. In conclusion, pharmaceutically prepared human IgG preparations contain variable but significant levels of high-avidity IFN alpha and IFN beta neutralizing antibodies.

Antibodies, Monoclonal↗

PubMed1995

Cytokine autoantibodies in rheumatoid arthritis.

Sera from 42 patients with rheumatoid arthritis (RA) and 40 healthy controls (HC) were examined for cytokine autoantibodies (CK-aAb) by accurate and sensitive radioimmunoassays. The prevalences of detectable CK-aAb in RA (HC) were: aAb-IL-1 alpha = 36% (38%); aAb-IL-6 = 29% (13%), p = 0.06; aAb-IL-8 = 0% (0%); aAb-IFN alpha = 12% (3%), p = 0.11. The levels of the individual CK-aAb did not correlate, and there were no correlations between CK-aAb levels and clinical or laboratory variables. CK-aAb levels remained constant in 8 RA patients tested over a period of 6 months. With regard to alterations in aAb-IL-1 alpha levels, 4/11 HC were consistently positive over 18-36 months; 2/11 converted and became highly positive. The levels of aAb-IFN alpha and aAb-IL-6, but not aAb-IL-1 alpha, tended to be increased in RA patients; aAb-IL-8 were undetectable in both RA and HC.

Adult↗

PubMed1995