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The optics of fundus examination.

It has been 140 years since the invention of the ophthalmoscope in 1851 by Herman von Helmholtz. Since then, a considerable amount of time and effort has been devoted to improving the clinician's view of the fundus both for diagnostic and therapeutic reasons. Recently, there have been some notable advances in this respect, such as the 90 diopter lens, the "2.2 pan retinal" lens, and numerous "wide angle" fundus-viewing contact lenses to which the Volk Quadraspheric fundus lens has been the most recent addition. This paper is a review of the optical principles underlying the methods of fundus examination currently available.

Fundus Oculi↗

A history of primary angle closure glaucoma.

The satisfactory control and cure of attacks of primary angle closure glaucoma spans one hundred years following von Graefe's iridectomy in 1856. Gonioscopy was required to validate the theories of shallow anterior chamber and pupillary obstruction, but the gonioscopists looked for the causes of angle closure in their own territory at the angle in the periphery of the anterior chamber and disregarded the center. General agreement of the importance of pupil block was thereby delayed for over ten years. Advances in pharmacology and the invention of laser surgery gave opthalmologists a comfortable control of a formerly distressing, blinding disease.

Glaucoma, Angle-Closure↗

Human uses of ultrasound: ancient and modern.

For untold millennia certain animals have used ultrasound to probe places where light is unavailable, echo-locating bats being among the most adept. With ultrasonics, bats can quickly and safely 'see' at night in pursuing insects or flying in dark caves. Unable to hear ultrasound, humans have nevertheless made use of it. They did this anciently by taming wolves, with their keen ultrasonic hearing, for aiding in the hunt. Currently, they are doing this by developing technology to detect, generate and process ultrasound for searching in air or other gases, in water or other liquids, and in solids. The story of these technological developments is a large and fascinating mirror of human history involving the advent of such discoveries and inventions as magnetostriction, piezoelectricity, sonar, ultrasonic microscopy, etc.--the list is long. By now we are skilled in probing for underwater objects, the internal structure in materials, organs inside the human body, etc.--again the list is long. A number of different ultrasonic systems can be categorized into one of three key generic approaches: pulse-echo exploration, intensity mapping, and phase-amplitude measurement. In addition, each of these categories can be combined with the others to produce hybrid systems for which an unambiguous categorization is difficult or impossible. Challenging problems remain but solutions are being found. New principles and techniques are being discovered that will improve the use of ultrasound. Employing tomo-holographic techniques to reduce ambiguity in probing three-dimensional objects, near-field techniques to boost resolution and using limited-diffraction beams to provide image construction with ultra high frame rates are cases in point.

Animals↗

Improved extraction procedures for polychlorinated biphenyls in solid samples with aqueous sodium hydroxide under autoclave conditions.

The efficacy of the extraction of polychlorinated biphenyls (PCBs) from varnish-infiltrated insulating papers as a model of solid materials with an aqueous sodium hydroxide (NaOH) by autoclaving at 121 degrees C for 30 min was compared with those for the conventional procedures, i.e., saponification with 1 N ethanolic NaOH in a boiling water bath for 60 min and extraction with benzene in a Soxhlet apparatus. The newly invented autoclaving method was found to be superior to the conventional ones, yielding approximately 5- to 6-fold cumulative PCB congeners without being accompanied by extended decomposition. Therefore, the autoclave-based sample treatment is recommended for more accurate determination of PCBs in the case of PCB-impregnated solid materials such as hardened oils and resin-coated or -infiltrated papers instead of being treated conventionally.

Chemistry Techniques, Analytical↗

A model for tool-use traditions in primates: implications for the coevolution of culture and cognition.

Inspired by the demonstration that tool-use variants among wild chimpanzees and orangutans qualify as traditions (or cultures), we developed a formal model to predict the incidence of these acquired specializations among wild primates and to examine the evolution of their underlying abilities. We assumed that the acquisition of the skill by an individual in a social unit is crucially controlled by three main factors, namely probability of innovation, probability of socially biased learning, and the prevailing social conditions (sociability, or number of potential experts at close proximity). The model reconfirms the restriction of customary tool use in wild primates to the most intelligent radiation, great apes; the greater incidence of tool use in more sociable populations of orangutans and chimpanzees; and tendencies toward tool manufacture among the most sociable monkeys. However, it also indicates that sociable gregariousness is far more likely to produce the maintenance of invented skills in a population than solitary life, where the mother is the only accessible expert. We therefore used the model to explore the evolution of the three key parameters. The most likely evolutionary scenario is that where complex skills contribute to fitness, sociability and/or the capacity for socially biased learning increase, whereas innovative abilities (i.e., intelligence) follow indirectly. We suggest that the evolution of high intelligence will often be a byproduct of selection on abilities for socially biased learning that are needed to acquire important skills, and hence that high intelligence should be most common in sociable rather than solitary organisms. Evidence for increased sociability during hominin evolution is consistent with this new hypothesis.

Animals↗

How did bacteria come to be?

Bacteria in the modern taxonomic sense are one of the three Domains. They must have split from the other two after the bulk of the development of biochemistry and cell biology had taken place. Up to the time of the Last Universal Ancestor (LUA) the world had been monophyletic with little stable diversity. This is to say that as advances took place the older forms were eliminated and diversity was only temporary. Two kinds of events could, in principle, permit stable diversity to arise. One kind occurs when two nearly simultaneous, different advances occur, both of which overcome the same problem. While the previous type would be supplanted, if the new types did not compete with each other, new niches and habitats could lead to stable diversity. The second kind is a saltation or macroevolutionary event that greatly expands the biota and reduces previous constraints and thereby drastically reduces competition; this generally leads to a 'species radiation' and results in the development of a spectrum of biological types some of which persist and do not compete with each other. It is proposed that the two splits to yield the three Domains of Bacteria, Archaea, and Eukarya, resulted from one of each of these two processes leading to diversity. One arose from the consequences of cells accumulating substances from the environment, thus increasing their internal osmotic pressure. This resulted in two nearly simultaneous biological solutions: one (Bacteria) was the development of the external sacculus, i.e. the formation of a stress-bearing exoskeleton. The other (Eukarya) was the development of cytoskeletons and mechanoenzymes, i.e. formation of an endoskeleton. The other event causing diversity was the invention of an effective way to tap a new energy source and allow the biomass to increase extensively permitting a radiation of many different types of organisms. I suggest that this seminal advance was the development of methanogenesis. This caused a short-lived expansion and radiation before oxygen-producing photosynthesis allowed a still more major expansion and decreased the number of methanogens. Some details of these processes are elaborated. In particular, the evolutionary process that permitted the development of a sacculus, interpreted in light of the bacterial physiology of today's organisms is presented. It is argued that many great advances arise by developing a number of totally different processes for other purposes that can then each be modified to combine for yet another purpose.

Archaea↗

HPLC-electrochemical detection of tocopherol products as indicators of reactive nitrogen intermediates.

The nitric oxide (NO) free radical serves diverse functions in mammalian physiology, facilitating processes that range from vasodilation to neurotransmission to host-pathogen defense. Despite the fascinating biochemical utility of this small diatomic gas, NO and its derived oxidation or reduction products [reactive nitrogen species (RNSs) or reactive nitrogen intermediates (RNIs)] can be deleterious to cells and tissues under conditions of pathophysiology. Recent years have witnessed a tremendous and continuing scientific interest in RNI, both as targets for pharmacotherapy and as biomarkers for disease. Accordingly, methods have been developed to quantify RNI in real time under controlled experimental conditions. Such methods usually employ either electron paramagnetic resonance (EPR) spin traps (see ) or electrochemical sensors (Cserey and Gratzl, 2001). Nonetheless, the transient nature of NO and RNIs often precludes their routine assessment in animal experiments or human clinical studies where tissue must be archived and stored at a later time. To circumvent these limitations, methods have been invented to detect and quantify stably nitrated products of RNI reaction with ambient biomolecules. This chapter describes the theory and methodology for detection of lipid-phase tocopherol nitration products, especially 5-nitro-gamma-tocopherol (5-NO2-gammaT) by high-performance liquid chromatography with electrochemical detection (HPLC-ECD).

Chromatography, High Pressure Liquid↗

Ubiquitin fusion technique and related methods.

The ubiquitin fusion technique, developed in 1986, is still the method of choice for producing a desired N-terminal residue in a protein of interest in vivo. This technique is also used as a tool for protein expression. Over the past two decades, several otherwise unrelated methods were invented that have in common the use of ubiquitin fusions as a component of design. I describe the original ubiquitin fusion technique, its current applications, and other methods that use the properties of ubiquitin fusions.

Amino Acid Sequence↗

Disrupting the brain to guide plasticity and improve behavior.

Neurones may be highly stable and nonplastic cellular structures, but they are engaged in dynamically changing, intrinsically plastic neural networks that provide a most energy efficient, spatially compact, and precise means to process input signals and generate adaptable responses to a changing environment. Neural plasticity is evolution's invention to enable the nervous system to escape the restrictions of its own genome (and its highly specialized cellular specification) and thus adapt to environmental pressures, physiologic changes, and experiences. At neural system level two steps of plasticity can be identified: unmasking existing connections that may be followed by establishment of new ones possibly even with integration of new neural structures and neurons. In any case, plastic changes may not necessarily represent a behavioral gain for a given subject, as they represent the mechanism for development and learning, as much as a cause of pathology and disease. The challenge is to learn enough about the mechanisms of plasticity to be able to guide them, suppressing changes that may lead to undesirable behaviors while accelerating or enhancing those that result in a behavioral benefit for the subject or patient. Neurostimulation, including noninvasive brain stimulation techniques, provide an opportunity to modulate brain plasticity in a controlled and specific manner. Such interventions to guide behavior or treat pathological symptomatology might be more immediate in their behavioral repercussion and thus more effective than approaches intent on addressing underlying genetic predispositions.

Animals↗

Adrenergic regulation of visuocortical plasticity: a role of the locus coeruleus system.

Noradrenaline-beta-adrenoceptor-mediated neural plasticity in cat visual cortex exemplifies clearly established roles of the locus coeruleus system in brain function. The prime role of the noradrenaline-beta-adrenoceptor system in the regulation of ocular dominance plasticity is discussed in this chapter and includes a newly invented paradigm of ocular dominance changes under anesthesia and paralysis without benefit of visual attention. Based on our recent findings, we have sought to integrate positive contributions of muscarinic cholinergic receptors to the beta-adrenoceptor-mediated regulatory processes. The issue of "activity dependency" is important and we recognize the necessity of designing new studies in which relationships between activity dependency within the visual pathway and global neurochemical/cellular factors can be tested directly. Further, we critically reviewed the involvement of gamma-aminobutyric acidA type receptors and N-methyl-D-aspartate receptors in the regulation of ocular dominance plasticity.

2-Amino-5-phosphonovalerate↗

Bipolar coagulation in neurosurgery.

Coagulation is an essential part of a surgical procedure, especially in neurosurgery. Beginning in the early years of this century, various techniques have been used to control bleeding at the surgical site. Over the years, these techniques have led to the invention of the bipolar coagulator and its modifications. Prevention of charring and tissue adhesion have been the goals of bipolar coagulator manufacturers all over the world; new techniques and different metallurgical compositions for the forceps have been tried to achieve these results. The NS2000, with its microprocessor-based controlled coagulative sequence, can be a good system for reducing tissue adhesion and charring under desired limits of low output power ranges provided by the system. Comparable results can also be obtained with the Malis CMC III and Synergy Malis systems with irrigation channels. These systems have the additional advantages of providing higher power outputs at lower panel settings and a maximum power output greater than that of NS2000. For neurosurgeons who need the additional option of cutting, the Malis CMC III is the recommended system.

Electrosurgery↗

Immunoperoxidase methods for the localization of antigens in cultured cells and tissue sections by electron microscopy.

We have presented our detailed methods for localizing antigens in cultured cells and tissue sections by IP at the EM level. Immunoperoxidase cytochemistry is particularly well suited for the study of sparse antigens as a result of the enzymatic amplification afforded by the method, and of molecules confined within a membrane-enclosed compartment wherein the DAB reaction produce can accumulate. Although IP is commonly used to localize membrane-compartmentalized molecules, reliable qualitative information can also be obtained on cytoplasmic antigens as well (Anderson et al., 1978; Merisko et al., 1986; Rodman et al., 1984). For these and other reasons, it is likely that IP cytochemistry will continue to be an important tool for the cell biologist especially in the study of membrane traffic. Other inventive combinations of immunocytochemical methods will likely be forthcoming, for example, combining IP localization with postembedding labeling by colloidal-gold conjugates to provide triple EM labeling.

3,3'-Diaminobenzidine↗

The moral tollbooth: a method that makes use of the patent system to address ethical concerns in biotechnology.

Patents granted for biotechnological innovations continue to cause social and ethical dilemmas. For example, much controversy surrounds the patenting of genes that predispose to breast-cancer, and in the USA the debate continues about whether or not stem-cell technology should be accessible to all. In this report, we argue that some of these concerns can be addressed within national patent systems. In particular, we examine the "order public or morality" clause that exists in most national patent procedures. Furthermore, we propose that patents for inventions that present social and ethical questions should be subject to suspension by an independent, transparent, and responsible tribunal made up of specialists in ethics, research, and economics. This suspension should be reversible so that, when the social or ethical concerns have been addressed in an appropriate manner, the suspension can be lifted. Although controversial, such a flexible mechanism would assist governments and industry in enhancing public support for patents in the biotechnology area.

Animals↗

Fictitious epilepsy.

32 children and 4 adults had extensive investigation and treatment for epilepsy because of false seizures invented or induced by a relative, usually the mother. They also suffered needless hospital admissions and restriction of education and activities. Follow-up of the children suggests a danger of abnormal illness behaviour continuing into adult life. For a few young children seizures are really anoxic episodes caused by the parent. In some cases these lead to brain damage and death, and an important association with sudden unexplained death of infancy (cot death) is emerging.

Adolescent↗

Development of glass-ionomer cement systems.

In the 1960s the idea of positive physico-chemical adhesion with tooth substance resulted in the invention of polyacrylic acid-based cements, first the zinc polycarboxylate and, subsequently, the glass-ionomer cements. These materials were shown to undergo specific adhesion with hydroxyapatite and proved to have properties satisfactory for a variety of clinical applications. The key properties of the glass-ionomer cements--fluoride release over a prolonged period and specific adhesion to enamel and dentine coupled with aesthetic qualities are related to their characteristics as aqueous polyelectrolyte systems. In order to improve toughness, speed of setting and resistance to dehydration, hybrid materials in which some of the water content of the glass-ionomer system was replaced by water-soluble polymers or monomer systems capable of ambient polymerization were formulated in the late 1980s. These materials, which have been termed resin-modified glass-ionomer cements, involve, ideally, the formation of an interpenetrating polymer network combining the acid-base cross-linking reaction of the metal ion-polyacid with the cross-linking polymerization of the monomer system or additive action of the polymers. In the predominantly resin materials there is little polyelectrolyte character and it is controversial whether such materials should be categorized as glass-ionomer cement systems. The specific advantages of these materials over traditional glass-ionomer systems and over composite restorative systems remain to be fully documented. Studies of adsorption to hydroxyapatite of typical monomers using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF SIMS) indicate that resistance to water displacement decreases as hydrophobicity increases.

Biocompatible Materials↗

Galvanic cultures: electricity and life in the early nineteenth century.

Electricity has long proved to be a powerful tool for investigating the properties of life. Towards the beginning of the nineteenth century new discoveries and inventions in electricity stimulated a new popular fascination with such questions. Electricity seemed a good way of understanding the machinery of life. It was the key to unlocking the secrets of vitality. Looking at these early nineteenth-century debates and discussions provides a good way of focusing on the cultural connections and ramifications of science. As electricity provided tools for understanding life, it provided tools for understanding culture also.

Animals↗

Montagu's variolation.

Lady Mary Wortley Montagu is sometimes mentioned by both medical and literary historians as the introducer to England of smallpox inoculation. Usually, the story is garbled by confusion with Edward Jenner's later invention, vaccination. Some historians have rejected her claim, arguing that the credit belongs to the medical establishment of the day. So just how much importance has this gifted amateur in the story of medical science?

Adult↗

Complement systems in invertebrates. The ancient alternative and lectin pathways.

The complement system in higher vertebrates is composed of about thirty proteins that function in three activation cascades and converge in a single terminal pathway. It is believed that these cascades, as they function in the higher vertebrates, evolved from a few ancestral genes through a combination of gene duplications and divergences plus pathway duplication (perhaps as a result of genome duplication). Evidence of this evolutionary history is based on sequence analysis of complement components from animals in the vertebrate lineage. There are fewer components and reduced or absent pathways in lower vertebrates compared to mammals. Modern examples of the putatively ancestral complement system have been identified in sea urchins and tunicates, members of the echinoderm phylum and the protochordate subphylum, which are sister groups to the vertebrates. Thus far, this simpler system is composed of homologues of C3, factor B, and mannose binding protein associated serine protease suggesting the presence of simpler alternative and lectin pathways. Additional components are predicted to be present. A complete analysis of this invertebrate defense system, which evolved before the invention of rearranging genes, will provide keys to the primitive beginnings of innate immunity in the deuterostome lineage of animals.

Amino Acid Sequence↗