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Claude Bernard set some of the boundaries for the program developed by himself in his Introduction à l'étude de la médicine expérimentale, which seems to be questioned by the very existence of biology of evolution and biology of development. Here, according to a Bernardian perspective, the author discusses possible fundamentals for this apparent limitation.
We describe a principle of reinforcement that draws upon experimental analyses of both behavior and the neurosciences. Some of the implications of this principle for the interpretation of behavior are explored using computer simulations of adaptive neural networks. The simulations indicate that a single reinforcement principle, implemented in a biologically plausible neural network, is competent to produce as its cumulative product networks that can mediate a substantial number of the phenomena generated by respondent and operant contingencies. These include acquisition, extinction, reacquisition, conditioned reinforcement, and stimulus-control phenomena such as blocking and stimulus discrimination. The characteristics of the environment-behavior relations selected by the action of reinforcement on the connectivity of the network are consistent with behavior-analytic formulations: Operants are not elicited but, instead, the network permits them to be guided by the environment. Moreover, the guidance of behavior is context dependent, with the pathways activated by a stimulus determined in part by what other stimuli are acting on the network at that moment. In keeping with a selectionist approach to complexity, the cumulative effects of relatively simple reinforcement processes give promise of simulating the complex behavior of living organisms when acting upon adaptive neural networks.
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The essay discusses a number of issues developed in several recent books on philosophical and ethical problems in the natural sciences, both pure (especially biology) and applied (especially medicine). The scaffolding of the discussion can be outlined as follows: Science is most coherently portrayed as a set of activities through which societies deal with a distinctive, but continually evolving set of interwoven practical, empirical, and conceptual problems. Consequently, approaches which attempt to delineate universal features of "scientific methods" or to depict the sciences as providing an approximation to an "objective" view of reality are much less enlightening than are analyses rooted directly in concrete scientific history and in the actual interplay of science with other social configurations. However, scientists are granted some meaningful autonomy in exercising their "curiosity" and there is a real sense in which scientific ideas and activities do possess momentum of their own. In other words, as is also true for other spheres, such as the arts, it is important not to fall into mechanical viewpoints which treat the movement of science as simply a derivative of forces generated elsewhere.
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A gene from Clostridium perfringens encoding a highly hydrophobic polypeptide of M(r) = 30,698 was cloned and sequenced. The polypeptide showed similarities with the inner membrane proteins of binding protein-dependent transport systems of the gram negative enterobacteria. The sequence homology to the UgpE and MalG proteins of Escherichia coli was 27.6%, or 60.4 and 52.2%, respectively, taking into account the conservative amino acid changes. The polypeptide contained the EAA---G---------(I/V)-LP motif of the gram negative transport proteins. This motif may thus be very old, as clostridia and E. coli separated some 1.5 x 10(9) years ago. The similarities suggest a common evolutionary origin of these genes.
LWBL is characterized by persistent and stable lymphocytosis, seen in but not exclusively female patients, with binucleated lymphocytes evident on peripheral blood smears. There is a polyclonal increase of serum IgM and in all cases immunophenotyping revealed a polyclonal expansion of B-lymphocytes. Whether this syndrome represents a premalignant disease process or a true polyclonal lymphocytosis remains unsettled. The occasional reports of clonal Ig rearrangements in this disorder suggest that in a minority of cases the polyclonal expansion may be followed by the emergence of one predominant clone. The demonstration of a clinically, benign, clonal lymphoid population is well recognised in several T cell disorders such as in the syndrome of large granular lymphocytes expansion. The benign clinical course and the lack of biological evolution in the majority of cases suggest that the importance of recognition of this disorder lies in avoiding aggressive therapy in these cases. A careful follow-up of these patients is mandatory and prospective immunological and genetic studies performed at different stages of the disease may well clarify this issue, particularly since most patients were HLA-DR7 positive.
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The human hepatitis B virus (HBV) and the duck hepatitis B virus (DHBV) share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames (ORFs) overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Most of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.
Biological evolution abides by an unbending rule obligating organisms to maintain energy equilibrium. Hypoxia reduces cellular energy supply and is thus thought to be deleterious. We report that cells have evolved pH-sensitive mechanisms to maintain energy equilibrium by lowering energy demand. We found that fermentation-induced acidosis allows hypoxic cells to maintain energy equilibrium and viability under hypoxia by restricting ribosomal biogenesis, the most energy-demanding cellular process. Acidosis triggers nucleolar condensation, decreases precursor rRNA synthesis, reduces the dynamic profile of the RNA polymerase I preinitiation factor UBF1 and its interaction with the promoter of rRNA genes (rDNA). These changes require the pH-dependent interaction of the statically detained von Hippel-Lindau tumor suppressor protein (VHL) with rDNA. This phenomenon is promoted by, but does not require, activation of the hypoxia-inducible factor (HIF), a transcription factor implicated in extracellular acidification, energy production and oxygen homeostasis. Abrogating this program by silencing VHL expression, competing rDNA-VHL interaction or preventing environmental acidification triggers energy starvation and cell death under hypoxia. Our data suggest that oxygen-starved cells maintain energy equilibrium by gauging the environmental concentration of H(+) to statically detain VHL to nucleolar rDNA and restrict ribosome production. These findings also provide an explanation for the protective effect of acidosis in ischemic settings such as development, stroke and cancer.
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The phylogeny of the genus Boettcherisca Rohdendorf was investigated by numerical techniques. The phenetic and phyletic dendrograms were obtained by mean character difference (MCD) and Russell and Rao's coefficient (SRR) proximity analyses and unweighted pair-group (UPGA) cluster analysis, and then related to the classification of the species group and the geographical distribution of the group. Two monophyletic and one paraphyletic groups were recognized: peregrina-group, septentrionalis-group and karnyi-group, respectively. A biological evolution was postulated commencing with a hypothetical ancestor having occurred in Sundaland and involving two lines of specialization, the peregrina-group found in and around Sundaland and the septentrionalis-group in Far East, Walacea and Papualand. On the basis of the cladogram and the present geographical distribution, a Sundaland origin was postulated for the genus.
The Authors report a case of renal hemangiopericytoma, whose interest is related to the extreme rarity (24 cases reported until today), its insidious growth, the late in diagnosis, its uncertain clinical-biological evolution, not always predictable. Considering chemotherapy and radiotherapy ineffectiveness, an adequate treatment for such a neoplasm requires the surgical therapy, which must be followed by a careful follow-up.
OBJECTIVE: To determine the safety and pharmacokinetics of an anti-tumour necrosis factor (TNF alpha) monoclonal antibody in the treatment of septic shock, and to evaluate the biological evolution of cytokine response. DESIGN: Open-label, prospective, pilot trial with escalating doses of a murine monoclonal antibody (B-C7) directed against TNF alpha. SETTING: University medical centre intensive care unit. PATIENTS: Nine patients with septic shock, who received standard supportive care and antimicrobial therapy in addition to the anti-TNF alpha antibody. INTERVENTIONS: Patients were treated intravenously with one of three escalating doses of B-C7 monoclonal antibody (MoAb): 0.4 mg/kg, 0.8 mg/kg, 1 mg/kg. RESULTS: MoAb was well tolerated despite the development of human anti-mouse antibodies (HAMA) for each patient; B-C7 plasma levels were dose-dependent. At study entry, TNF alpha and IL-6 levels were detected in six and seven patients respectively; IL-1 levels were low and interferon-gamma was undetectable. CONCLUSIONS: No side effects were noted during treatment regardless of the dose used; however, further studies are needed to determine the clinical efficacy of this agent in septic shock.
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