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PubMed2004

Sherlock Holmes: scientific detective.

Sherlock Holmes was intended by his creator, Arthur Conan Doyle, to be a 'scientific detective'. Conan Doyle criticized his predecessor Edgar Allan Poe for giving his creation - Inspector Dupin - only the 'illusion' of scientific method. Conan Doyle believed that he had succeeded where Poe had failed; thus, he has Watson remark that Holmes has 'brought detection as near an exact science as it will ever be brought into the world.' By examining Holmes' methods, it becomes clear that Conan Doyle modelled them on certain images of science that were popular in mid- to late-19th century Britain. Contrary to a common view, it is also evident that rather than being responsible for the invention of forensic science, the creation of Holmes was influenced by the early development of it.

England↗
PubMed2005

Michael Faraday, media man.

Michael Faraday was an enthusiastic portrait collector, and he welcomed the invention of photography not only as a possible means of recording observations accurately, but also as a method for advertising science and its practitioners. This article (which is part of the Science in the Industrial Revolution series) shows that like many eminent scientists, Faraday took advantage of the burgeoning Victorian media industry by posing in various roles.

Communications Media↗
PubMed2004

Attention deficit hyperactivity disorder (ADHD) in a 19th century children's book.

Attention deficit hyperactivity disorder (ADHD) is a major mental disorder in children. Presently, its pathogenesis and treatment as well as its role in adult psychiatry are subjects of heated debate. As early as 1846, the typical symptoms of ADHD were described by Heinrich Hoffmann, a physician who later founded the first mental hospital in Frankfurt. Interestingly, his description was published in a children's book entitled "Struwwelpeter" which he had designed for his 3-year-old son Carl Philipp. The symptomatology is impressively depicted in the colourfully illustrated story of "Zappel-Philipp" ("Fidgety Philip"), probably the first written mention of ADHD by a medical professional. This clearly shows that the diagnosis of ADHD is not an "invention" of modern times.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Mice and flies and monkeys too: caloric restriction rejuvenates the aging immune system of non-human primates.

Humanity has been obsessed with extending life span and reversing the aging process throughout recorded history and this quest most likely preceded the invention of the written word. The search for eternal youth has spurred holy wars and precipitated the discovery of the new world (the 'Fountain of youth'). It therefore comes as no surprise that an increasingly greater amount of research effort is dedicated to improve our understanding of the aging process and finding interventions to moderate its impact on health. Caloric restriction (CR) is the only intervention in biology that consistently extends maximal and median life span in a variety of short-lived species. Several theories to explain the mechanisms of action of CR have been put forth, including the possibility that CR acts by retarding immune senescence. The question remains, however, whether CR will have the same beneficial impact on human aging, and, if so, how long does CR need to last to produce beneficial effects. To address this question, several groups initiated long-term studies in Rhesus macaques (RM) in the 1980s. Here, we review published data describing the impact of CR on the aging immune system of mice and primates, and discuss our unpublished data that delineate similarities and differences in the effects of CR upon T cell aging and homeostasis between these two models.

Aging↗
PubMed2005

Intracytoplasmic sperm injection: a novel selection method for sperm with normal frequency of chromosomal aneuploidies.

OBJECTIVE: To test a newly invented intracytoplasmic sperm injection (ICSI) sperm selection method based on sperm hyaluronic acid (HA) binding. DESIGN: Comparison of chromosomal disomy and diploidy frequencies in sperm arising from semen and in HA-bound sperm. SETTING: Academic andrology laboratory. PATIENT(S): Men presenting for semen analysis. INTERVENTION(S): Washed sperm fractions of 32 semen samples were applied to Petri dishes or glass slides coated with immobilized HA. The unbound sperm were rinsed gently, and the HA-bound sperm were removed with an ICSI pipette. The control sperm population was the unselected sperm. Both HA-selected and unselected sperm were treated with fluorescence in situ hybridization with centromeric probes for the X, Y, and 17 chromosomes. MAIN OUTCOME MEASURE(S): Chromosomal disomy and diploidy frequencies. RESULT(S): In the HA-bound sperm (495-2,079 per man, 41,670 in all) compared with unselected sperm (4,770 per man, 162,210 in all), the chromosomal disomy frequencies were reduced to 0.16% from 0.52%, diploidy to 0.09% from 0.51%, and sex chromosome disomy to 0.05% from 0.27% (a 5.4-fold reduction vs. 4-fold respective increase in ICSI offspring). CONCLUSION(S): The HA sperm selection method for ICSI, which is based on a relationship between sperm receptors for zona pellucida and HA, will likely reduce the potential genetic complications and adverse public health effects of ICSI.

Andrology↗
PubMed2006

Fibronectin EIIIA splicing variant: a useful contribution to forensic wounding interval estimation.

A fibronectin splicing variant, Fn containing an extra type III domain (EIIIA in rat, ED1 or EDA in human) has recently attracted more attention because of its sensitive response in injury of adult tissue. The characteristic that this form is absent in adult tissue while it is commonly expressed in fetal tissues and injured adult tissue is useful in estimation of injury interval in forensic science. The regulation of fibronectin splicing was studied by immunohistochemistry by using monoclonal antibody to EIIIA on sections from paraffin embedded rat skin sample after contusion. The results indicated that epidermic cells and hair follicle epithelium of rat skin were found positive staining at 6h after injury, and the color became darker with prolonged wounding time. Based on the above result, we invented a type of test paper assayed for EIIIA-Fn splicing variant by using immune colloidal gold technique. After dipping one end of test paper in the supernatant fluid of tissue homogenates of injury skin for few minutes, detecting line could be found. It showed that all experimental injured samples revealed positive staining; the darkness of positive staining was dependent on the injury time, while control normal skin cannot found positive staining. It is concluded that there is a close relationship between the expression of EIIIA-Fn splicing variant and wounding interval, and that the gold-labeled test paper can be useful in distinguishing ante- and post-mortem injury, and in estimation of wounding interval in forensic science.

Alternative Splicing↗
PubMed2004

Start-up entities in the origin of new genes.

The remarkable diversity in the contents of genomes raises questions about how new genes and new functions originate. Recent evidence indicates that parasitism, particularly the molecular interactions between phage and their bacterial hosts, is a likely mechanism for generating new genes. This invention of such novel functions seems to be founded on a strategy that secures the short-term survival of parasitic elements and thereby contributes to the renovation of gene repertoires in their host.

Animals↗
PubMed2006

The role of PillCam endoscopy in Crohn's disease: the European experience.

The European experience of wireless capsule endoscopy (WCE) inCrohn's disease (CD) is presented. Evidence from prospectivestudies comparing WCE with standard methods speaks in favor ofWCE as the method with the highest sensitivity for diagnosingsmall intestinal CD. WCE is likely to be helpful in diagnosing CD,in determining the extent of the disease, and in providing infor-mation on which of the current treatment approaches are specifi-cally effective within the small intestine. Although the invention ofthe patency capsule was helpful for diagnosing and characterizingsmall bowel strictures, the problem of capsule retention in CDpatients remains a controversial issue.

Crohn Disease↗
PubMed2005

[Thierry's spatula instrumental extraction: a study of foetal-maternal morbidity].

OBJECTIVE: Assisted delivery is necessary in many obstetrical conditions but is involved in maternal and foetal complications. The legal pressure and the commendable aim consisting in less neonatal morbidity and mortality have called forth a reflection about the type and the way of instrumental foetal extraction. In 1950, Thierry had already felt this problem and he invented spatula to replace obstetrical forceps. Although this instrument appears empirically little deleterious, literature about its evaluation is very poor. We studied this instrument in a retrospective 190 cases series. PATIENTS AND METHOD: Retrospective study of 190 Thierry's spatula extractions, over a seven-year period (January 1996 to December 2002), at the Centre Hospitalier General of Montbeliard. RESULTS: Out of a total of 8126 deliveries for the study period, the instrumental extraction rate was 5.3%, with 40.6% spatula extractions (190 cases). No failure of Thierry's spatula extraction was noted. DISCUSSION ET CONCLUSION: Our study concludes that spatula is efficient but does not usually permit anterior rotation of occipito-posterior presentation. Maternal and foetal morbidity is not frequent.

Birth Injuries↗
PubMed2004

Bacterial biofilm formation on urologic devices and heparin coating as preventive strategy.

In the process of endourological development a variety of foreign bodies have been invented besides urinary catheters, on which biofilm can be formed. Bacteria in the biofilm are less susceptible to antibiotics. An additional problem of medical biomaterials in the urinary tract environment is the development of encrustation and consecutive obstruction. The most promising prevention strategy for bacterial biofilms is the production of materials with anti-adhesive surfaces such as heparin. Although heparin-coated ureteral stents are expensive, they justify their cost. Our studies show that such devices are protected against incrustation and biofilm formation for a longer period of time: 6-12 months, both in vitro and in vivo.

Bacteria↗
PubMed2006

Emergent CSCW systems: the resolution and bandwidth of workplaces.

In any collaborative work settings, people naturally develop physical tools and associated work processes that support the management of the interdependencies in information, materials, and social needs. Field studies of management of operating rooms pointed out that collaborative work is supported by an infrastructure that is composed of mostly non-computerized, physical components. The supporting infrastructure is jointly maintained and exploited, with constantly evolving patterns of usage, in response to complexity of coordination needs and the uncertain environment. To represent status and plans, users seem to invent structures based both on idiosyncratic preferences and on negotiated symbols. The fluidity and ease of restructuring workplaces to support collaborative work may be explained in part by the high resolution and bandwidth of workplaces: a large number of ways in which workers could structure their work and a high capacity to convey rich information and meanings quickly to collaborators. We argue that to support health care workers, designers of computer supported cooperative work (CSCW) systems should learn how the physical and perceptual properties of workplaces are exploited, and that CSCW systems should be designed to allow maximum freedom of restructuring and reconfiguring as part of workplaces to enhance bandwidth and resolution of representation and communication.

Cooperative Behavior↗
PubMed2004

DNA microarrays: from structural genomics to functional genomics. The applications of gene chips in dermatology and dermatopathology.

The human genome project was successful in sequencing the entire human genome and ended earlier than expected. The vast genetic information now available will have far-reaching consequences for medicine in the twenty-first century. The knowledge gained from the mapping and sequencing of human genes on a genome-wide scale--commonly referred to as structural genomics--is prerequisite for studies that focus on the functional aspects of genes. A recently invented technique, known as gene chip, or DNA microarray, technology, allows the study of the function of thousands of genes at once, thereby opening the door to the new field of functional genomics. At its core, the DNA microarray utilizes a unique feature of DNA known as complementary hybridization. As such, it is not different from Southern (DNA) blot or northern (RNA) blot hybridizations, or the polymerase chain reaction, with the exception that it allows expression profiling of the entire human genome in a single hybridization experiment. The article highlights the principles, technology, and applications of DNA microarrays as they pertain to the field of dermatology and dermatopathology. The most important applications are the gene expression profiling of skin cancer, especially of melanoma. Other potential applications include gene expression profiling of inflammatory skin diseases, the mutational analysis of genodermatoses, and polymorphism screening, as well as drug development and chemosensitivity prediction. cDNA microarrays will shape the diagnostic approach of the dermatology and the dermatopathology of the future and may lead to new therapeutic options.

Dermatology↗
PubMed2005

96-Well solid-phase extraction: a brief history of its development.

This communication describes the invention and further development of the first 96-well solid-phase extraction system and the original purposes to which it was put. We also describe the adaption of this system for bioanalysis of pharmaceutically active small molecules and the needs underlying it. The system has become a world-wide standard for high-throughput bioanalysis and has been extended by others to include, for example, disk-phase extraction and supported liquid-liquid extraction, as well as 384-well systems. The factors that enabled this leap forward in productivity are discussed.

Chromatography, Liquid↗
PubMed2004

Evaluation of novel one-step dry-coated tablets as a platform for delayed-release tablets.

Using a novel one-step dry-coated tablets (OSDRC) manufacturing method, which we have recently invented, we evaluated the possibility of its application to delayed-release tablets. The manufacturing method for OSDRC is different from conventional methods in that dry-coated tablets can be made with only one process. One of the major advantages of OSDRC is that we can expect to produce tablets, which always contain the core exactly in the center of the whole tablet. This characteristic means that the thickness of outer layer is constantly uniform, which is difficult to achieve with the conventional dry-coated tablets. The effects of different outer layer thicknesses and various compression pressures were examined using HPMC to evaluate OSDRC applicability to delayed-release tablets. We proved that the lag-time can be adjusted only by changing the thickness of the outer layer without any arrangement of its ingredients, which is quite different from the conventional approach. Further, the lag-time of each OSDRC prepared in the 100-200 MPa compression pressure range was almost the same, indicating the lag-time of OSDRC under these compression pressures does not vary. The release rate of the drug (acetaminophen) from the OSDRC with 0.5 and 1.0 mm outer layer thicknesses was almost constant independent of compression pressure. On the other hand, the release rate of the OSDRC with a 2.0 mm outer layer thickness was delayed compared to that of other thicknesses. That is, in the tablets with 2.0 mm outer layer thickness, the release rate declined since its outer layer thickness was sufficient to form a gel-layer. In conclusion, OSDRC could be a platform for delayed-release tablets, which do not utilize the conventional method used for dry-coated tablets.

Acetaminophen↗
PubMed2006

In vitro biocompatibility of a novel Fe2O3 based glass ionomer cement.

INTRODUCTION: Since their invention in the late 1960s, glass ionomer cements (GICs) have been used extensively in dentistry but recently they have also been utilised in ear nose and throat (ENT) surgery. Unfortunately, Al3+, a component of conventional ionomer glasses, has been linked to poor bone mineralisation and neurotoxicity. OBJECTIVE: The aim of the research was to modify a commercial ionomer glass composition by substituting Al2O3 with Fe2O3. METHODS: Glasses with the following molar compositions were fabricated: 4.5SiO2*3M2O3*XP2O5*3CaO*2CaF2 (M = Al or Fe, X = 0-1.5). The glasses were characterised using X-ray fluorescence (XRF) and X-ray powder diffraction (XRD). Cements were prepared using a standard ratio of; 1 g of glass powder: 0.2 g of dried polyacrylic acid: 0.3 g of 10% tartaric acid solution. Cement formation was assessed using a Gilmore needle and in vitro biocompatibility was investigated for novel cement formulations. RESULTS: XRF revealed that the Fe2O3-based glasses had Al2O3 contamination from the crucibles and also had undergone substantial F- losses. XRD gave peaks that corresponded to magnetite Fe3O4 (JCPDS # 19-629) in all compositions. Apatite Ca5(PO4)3(OH,F) (JCPDS # 15-876) was identified in P2O5 containing glasses. It was possible to fabricate cements from all of the Fe2O3-based ionomer glasses. Good in vitro biocompatibility was observed for the Fe2O3-based cements. CONCLUSION: Ionomer glasses may be prepared by entirely replacing Al2O3 with Fe2O3. Cement setting times appeared to be related to P2O5 content. Fe2O3-based cements showed good in vitro biocompatibility.

Animals↗
PubMed2005

Heartbeat patterns during the postembryonic development of Drosophila melanogaster.

Pulsations of the dorsal vessel were recorded in vivo during the whole postembryonic development of D. melanogaster, by means of a newly invented, pulse-light opto-cardiographic method. The young larvae of the 1st and 2nd instars submerged in the feeding medium exhibited extremely high rates of heartbeat, 7Hz at room temperature. These values are among the highest rates of heartbeat ever recorded in the animal kingdom. The fully grown larvae of the 3rd instar showed approximately half of the maximum heartbeat rate (3.5-4Hz), which became stabilized after pupariation to 2.5-2.7Hz. The larval heartbeat was always uni-directional, in the forward-oriented or anterograde direction and it was almost continuous. The slowly disintegrating, old larval heart used to beat at the constant frequency of 2.5-2.7Hz until complete cessation of all cardiac functions in 1-day-old puparium. In spite of the persisting constant heartbeat frequency, the transformation process of the larval heart was associated with successively decreasing amplitude of the systolic contractions and with the prolongation of the resting periods. The newly formed heart of the pupal-adult structure exhibited a qualitatively new pattern of heartbeat activity, which was manifested by periodic reversal of the heartbeat with the faster anterograde and slower retrograde phases. The frequencies of both of these reciprocal cardiac pulsations gradually increased during the advanced pharate adult period, reaching the values of 4-5Hz at the time of adult eclosion. Adult males and females also exhibited a perfect pattern of heartbeat reversal, with still very high rates of the anterograde heartbeat, in the range of 5-6Hz. In addition to the cardiac functions, we have recorded several kinds of extracardiac pulsations, which often interfered severely with the recordings of the heartbeat. There were strong, irregular extracardiac pulsations of a neurogenic nature (somatic muscles, oral armature) and relatively slow extracardiac pulsations of a myogenic nature (intestinal peristaltics, 0.2-0.3Hz). The extracardiac and cardiac pulsations were independent, their functions were not correlated. A possibility of creating new challenges in combination of molecular biology with the functional physiology of the heart have been discussed.

Animals↗
PubMed2004

Inactive enzyme-homologues find new function in regulatory processes.

Although the catalytic center of an enzyme is usually highly conserved, there have been a few reports of proteins with substitutions at essential catalytic positions, which convert the enzyme into a catalytically inactive form. Here, we report a large-scale analysis of substitutions at enzymes' catalytic sites in order to gain insight into the function and evolution of inactive enzyme-homologues. Our analysis revealed that inactive enzyme-homologues are not an exception only found in single enzyme families, but that they are represented in a large variety of enzyme families and conserved among metazoan species. Even though they have lost their catalytic activity, they have adopted new functions and are now mainly involved in regulatory processes, as shown by several case studies. This modification of existing modules is an efficient mechanism to evolve new functions. The invention of inactive enzyme-homologues in metazoa has thereby led to an enhancement of complexity of regulatory networks.

Enzymes↗
PubMed2004

Direct observation of Abeta amyloid fibril growth and inhibition.

Amyloid fibril formation is a phenomenon common to many proteins and peptides, including amyloid beta (Abeta) peptide associated with Alzheimer's disease. To clarify the mechanism of fibril formation and to create inhibitors, real-time monitoring of fibril growth is essential. Here, seed-dependent amyloid fibril growth of Abeta(1-40) was visualized in real-time at the single fibril level using total internal reflection fluorescence microscopy (TIRFM) combined with the binding of thioflavin T, an amyloid-specific fluorescence dye. The clear image and remarkable length of the fibrils enabled an exact analysis of the rate of growth of individual fibrils, indicating that the fibril growth was a highly cooperative process extending the fibril ends at a constant rate. It has been known that Abeta amyloid formation is a stereospecific reaction and the stability is affected by l/d-amino acid replacement. Focusing on these aspects, we designed several analogues of Abeta(25-35), a cytotoxic fragment of Abeta(1-40), consisting of l and d-amino acid residues, and examined their inhibitory effects by TIRFM. Some chimeric Abeta(25-35) peptides inhibited the fibril growth of Abeta(25-35) strongly, although they could not inhibit the growth of Abeta(1-40). The results suggest that a more rational design of stereospecific inhibitors, combined with real-time monitoring of fibril growth, will be useful to invent a potent inhibitor preventing the amyloid fibril growth of Abeta(1-40) and other proteins.

Circular Dichroism↗