Brain evolution in Old World monkeys.

Sulcal patterns of 14 genera of Old World monkeys were analyzed from 107 endocasts. Colobines and cercopithecines differ in patterns of cerebral convolutions, and functional and evolutionary hypotheses are here proposed regarding those differences. The cercopithecine pattern seems to be the more derived since it suggests relative expansion of prefrontal, and inferior temporal integration cortices as compared to the colobine pattern.     

Kinetic mechanisms of inhibitor binding: relevance to the fast-acting slow-binding paradigm.

Although phlorizin inhibition of Na+-glucose cotransport occurs within a few seconds, 3H-phlorizin binding to the sodium-coupled glucose transport protein(s) requires several minutes to reach equilibrium (the fast-acting slow-binding paradigm). Using kinetic models of arbitrary dimension that can be reduced to a two-state diagram according to Cha's formalism, we show that three basic mechanisms of inhibitor binding can be identified whereby the inhibitor binding step either (A) represents, (B) precedes, or (C) follows the rate-limiting step in a binding reaction. We demonstrate that each of mechanisms A-C is associated with a set of unique kinetic properties, and that the time scale over which one may expect to observe mechanism C is conditioned by the turnover number of the catalytic cycle. In contrast, mechanisms A and B may be relevant to either fast-acting or slow-binding inhibitors. However, slow-binding inhibition according to mechanism A may not be compatible with a fast-acting behavior on the steady-state time scale of a few seconds. We conclude that the recruitment hypothesis (mechanism C) cannot account for slow phlorizin binding to the sodium-coupled glucose transport protein(s), and that mechanism B is the only alternative that may explain the fast-acting slow-binding paradigm.     

IL-1 induces high affinity IL-2 receptor expression of CD4-8- thymocytes

We investigated the role of cytokines for the growth of CD4-8-thymocytes (double negative thymocytes) (DNT) in vitro and found that IL-1-induced IL-2-dependent proliferation of only the IL-2R-positive DNT subpopulation. The presence of IL-1 during the first 18 h of culture was sufficient for an optimal response and suggested that IL-1 induced DNT differentiation. We could indeed show by RNA dot blot analysis that IL-1 stimulated de novo expression of the p55 chain of the IL-2R thus initiating high affinity IL-2 binding and a proliferative response. Because macrophages and epithelial cells in the thymus produce IL-1 we propose that IL-1 is involved in early events during maturation of immature thymocytes.     

Nonspecific and selective stimulation of the immune system in the treatment of carcinoma in humans.

The experience of the Toronto General Hospital in the use of nonspecific stimulation of the immune system with bacille Calmette-Guérin (BCG) for the treatment of cancer of the gastrointestinal tract, malignant melanoma and breast cancer is described. The results are presented in terms of survival curves. The use of BCG administered intraperitoneally in a randomized study of patients with gastric, pancreatic and colorectal cancer proved of no benefit. On the other hand, when BCG was given orally in a randomized study of patients with resectable cancer of the colon and in nonrandomized consecutive studies of patients with malignant melanoma and stage IV carcinoma of the breast survival was increased. In a group of patients with advanced gastrointestinal cancer selective stimulation of the immune system with NED 137 produced a significant increase in survival when compared with the survival of historical controls (the patients given BCG intraperitoneally along with 5-fluorouracil for gastrointestinal cancer). The results of these studies suggest the need for a more rational approach in manipulating the immune response that would combine chemotherapy with selective stimulation of the immune system.     

How to build an inexpensive cyclotherm instrument for automated polymerase chain reaction

The Cyclotherm instrument is a functionally fully equivalent but inexpensive alternative to commercial instruments for automated polymerase chain reaction (PCR). It can be rebuilt under conditions of a biochemical laboratory for less than +1000. A Peltier element is used for heating and cooling of the reaction vials and the temperature and timing of the PCR cycles are controlled by a BASIC program in a SHARP PC 1600 low cost computer.     

The real objective of Mendel's paper: A response to Monaghan and Corcos

Mendel's work in hybridization is ipso facto a study in inheritance. He is explicit in his interest to formulate universal generalizations, and at least in the case of the independent segregation of traits, he formulated his conclusions in the form of a law. Mendel did not discern, however, the inheritance of traits from that of the potential for traits. Choosing to study discrete non-overlapping traits, this did not hamper his efforts.     

The Taung endocast: a reply to Holloway

Indices of rostrality (ir, ir') are developed to assess the extent to which the medial end of the lunate sulcus (L) is rostrally positioned in photographs and figures of lateral views of primate brains and endocasts, and indices are determined for chimpanzees, SK 1585 and the Taung endocast. Ir quantifies the extent of rostrality as it has traditionally been viewed (in A-P projections) while ir' takes dorsal curvature into account. The ir of the feature that I have identified as the lunate sulcus of Taung is within one standard deviation of the mean ir for Pan and its ir' is within 1.5 standard deviations from the mean ir' for Pan. Both findings are compatible with my earlier statement that the medial end of the lunate sulcus of the Taung endocast is in a pongid-like position. Use of stereoplotting to transfer the position of L from chimpanzee endocasts and brains to australopithecine endocasts is critically assessed: Holloway stereoplotted five chimpanzee brains and then transferred their mean coordinates that describe the lunate sulcus to the Taung endocast. If stereoplotting successfully transfers the extent to which L is rostrally located, one would expect the mean L of Pan and its transferred counterpart in Taung to have identical index values of rostrality. However, the ir of the lunate sulcus that Holloway located on Taung is over two standard deviations lower than the mean ir for the five chimpanzees he stereoplotted to determine its angular coordinates, and Holloway's ir' for Taung is one standard deviation lower than the five chimpanzees' mean ir'. These discrepancies are shown to be due to shape differences, and it is concluded that stereoplotting should not be used to transfer sulci between differently shaped endocasts without correcting for these differences. I also reply to Holloway's criticisms of my use of L/H indices, palpation, techniques for sampling endocasts, and illustration of the Taung endocast. It is shown that there is room on the Taung specimen for the lateral end of L, and the pongid-like sulcal pattern of Taung is reaffirmed. Thus, we do not yet know when human-like sulcal patterns first appeared in the hominid fossil record.