bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial gingivitis in dogs
Authors: Schroeder H. E. , Graf‐De Beer M. , Attström R.
Published: June 2006

The gingival characteristics after four days of gingivitis development have been studied in three Beagle dogs. Gingival normality was induced by regular tooth cleaning and gingivitis was provoked by abolishing oral hygiene procedures and giving the animals a soft diet. Measurements of the gingival fluid flow and the amount of crevicular leukocytes served to clinically assess the gingival condition. Semi‐ and ultra‐thin sections from contralateral biopsies of buccal gingival tissues from premolars obtained on day 0 and day 4 respectively were subjected to stereologic analysis based on morphometric point counting procedures. On day 0 of the experiment two dogs revealed minute amounts of gingival fluid and crevicular leukocytes and the gingival tissues of these dogs were normal. The third dog had somewhat higher amounts of the gingival parameters and the connective tissue adjacent to the junctional epithelium harboured a small lymphoid infiltrate occupying 8.3 ± 2.8% of the gingival tissues. On day 4 the gingival fluid flow and the amounts of crevicular leukocytes were increased in all dogs compared to their values on day 0.

The coronal con nective tissue in the two dogs with initially normal gingiva revealed on day 4 an infiltrated portion which occupied 6.1 ± 2.4% of the gingival tissues. The infiltrate was predominated by neutrophilic granulocytes, monocytes, macrophages, immunoblasts and small lymphocytes. A 60% loss of the collagen density in the infiltrated fraction was noted between biopsies from day 0 and day 4 in these two dogs. The tissues of the dog which entered the experiment with a preestablished lymphoid infiltrate reacted with similar but more intense inflammatory processes on day 4 than those of the dogs with normal gingiva on day 0.

The results indicate that initial gingivitis in dogs is characterized by acute exudative inflammation and immunopathological processes as well as by a marked loss of collagen fibers in the connective tissue located beneath the coronal part of the junctional epithelium. Possible mechanisms responsible for the observed alterations have been discussed.
Experimental periodontal disease in rats induced by plaque‐forming microorganisms
Authors: van der Hoeven J. S. , Mikx F. H. M. , Plasschaert A. J. M. , Maltha J. C.
Published: June 2006

Three different capsule or extracellular slime producing microorganisms: Rothia, Neisseria and Bacterionema were tested in SPF Osborne‐Mendel rats for their ability to stimulate plaque formation and their effect on the gingiva. Gingival inflammation in the rats was evaluated in histological sections of buccal gingivae.

All three the test strains were found to stimulate plaque formation. The high plaque score in the inoculated groups of rats was found to be attended by an increase in the area of infiltrated gingival tissue.
Ultrastructural changes in the microvasculature following cryosurgery of oral mucosa
Authors: Whittaker D. K.
Published: June 2006

Ultrastructural studies on vessels in oral mucosa subjected to surface freezing were carried out. Only minor changes were visible in the first 30 mins. post operatively but after this time both capillaries and venules were involved in a delayed prolonged response which was similar in character to that following certain other stimuli but which had some unique characteristics. The deposition of carbon in these experiments was compatible with increased permeability of the vessels and the ensuing lack of carbon labelling was shown to be due to the onset of platelet thrombosis. Structural endothelial damage was produced following the freezing episode and occurred prior to the time expected if anoxia were the reason for the vessel damage. There was no evidence that the presence of ice crystals during freezing produced direct rupture of vessels.
Influence of experimental neutropenia in dogs with chronic gingivitis
Authors: Rylander Harald , Attström Rolf , Lindhe Jan
Published: June 2006

The influence of a four day period of experimental neutropenia on the clinical state and the structural constituents of chronically inflamed gingiva has been studied in four beagle dogs. Neutropenia was induced by heterologous anti‐neutrophil serum. The effects on the gingiva were evaluated by Gingival Index (GI) and Gingival Exudate measurements and by morphometric analysis of various tissue components in sections from biopsies of buccal gingiva sampled on days 2, 3, and 4. Control biopsies were obtained before induction of neutropenia. The GI did not markedly change during the observation period. The amount of Gingival Exudate, however, significantly decreased following the induction of neutropenia and remained low throughout the experiment. Neutrophilic granulocytes disappeared in the gingival tissues, while, apart from a relative increase in plasma cells, no other tissue components seemed to change. No bacterial invasion of the junctional epithelium or of the gingival connective tissue could be observed. Thus during a four day period the bacterial defense mechanisms at the dentogingival junction seem to be able to prevent penetration of microorganisms into the gingival tissues despite the absence of neutrophilic granulocytes.
Cellular response to subgingival injection of bacterial products in the rat
Authors: Irving J. T. , Heeley J. D. , Socransky S. S.
Published: June 2006

Various bacterial products were injected in the oral mucosa of 74 conventional weanling rats of the Holtzman strain. The site of injection was lingual to the mesial cusp of the first molar of the maxilla or mandible. The bacterial products were whole dead cells, cell walls or cytoplasm obtained from Actinomyces naeslundii. Saline was injected into control animals. The animals were killed at intervals 0 to 48 hours subsequently, and the tissues examined by standard histological methods.

In all cases there was an initial polymorphonuclear response at the site of injection which had usually disappeared by 24 hours. In addition, osteoblasts on the adjacent alveolar bone were destroyed and in no case had they reappeared at 48 hours. Osteocytes were also missing after whole dead cell or cytoplasm injections, but not after cell wall injections. The most striking difference between the various reactions was an early appearance of lymphocytes after cell wall injections, which overshadowed the polymorphonuclear response, and which persisted up to 24 hours post injection. The disappearance of osteoblasts and osteocytes after injection of bacterial products from an organism associated with periodontal disease in man may explain in part the bone loss in this condition.
Two years oral use of chlorhexidine in man
Authors: Löue Harald , Rindom Schiöutt C. , Glavind L. , Karring T.
Published: June 2006

The general objectives of this study were to examine the long term effects of daily chlorhexidine application on the development of dental plaque, calculus and periodontal pathology and to monitor changes in oral microbiology and any systemic or local side effects following prolonged use of chlorhexidine over a period of two years.

An experimental group of 61 medical and dental students used 10 ml. of 0.2 per cent aqueous solution of chlorhexidine gluconate daily in addition to tooth brushing and interdental cleansing. A control group of 59 students used a placebo solution in addtion to tooth brushing and interdental cleansing. Assessment of selected oral and systemic parameters took place at regular intervals throughout the experiment.

The results show that, when compared to the placebo solution, chlorhexidine treatment reduced plaque and gingivitis, but tended to stain teeth. Stains were readily removed by a conventional dental prophylaxis procedure. The chlorhexidine group tended to exhibit a greater amount of supragingival calculus. There were no other local side effects relative to the structure and function of the oral mucosa, tongue, salivary glands and pharyngeal complex, following the prolonged use of chlorhexidine.
Two year oral use of chlorhexidine in man
Authors: Rindom‐Schiöutt C. , Löue H. , Briner W. W.
Published: June 2006

During two years of daily use of chlorhexidine mouthrinses 61 students, as well as 59 students using a placebo solution, had determinations of hemoglobin, methemoglobin, sedimentation rate, and numbers of erythrocytes and white cells as well as differential counts. The urine was examined for protein and glucose, and at the end of the experimental period the liver function and kidney function were tested. During the course of the study each participant responded regularly to a general health questionnaire. All the results remained negative, remained within normal range, or returned to normal values. No systemic or local side effect that could be attributed to the use of chlorhexidine was observed.
Two years oral use of chlorhexidine in man
Authors: Mackenzie I. C. , Nuki K. , Löue H. , Rindom Schiöutt C.
Published: June 2006

Possible changes in the structure of human oral mucosa resulting from exposure to chlorhexidine were examined in biopsy specimens of palatal and gingival mucosa obtained from three groups of young adults who had rinsed for more than 1 year (a) once or (b) twice daily with 0.2 % chlorhexidine solution or (c) with a placebo mouthwash. Specimens were quenched in liquid nitrogen and cryostat sectioned perpendicular to the epithelial surface. Sections stained with hematoxylin and eosin were used to assess the degree of keratinization of epithelia and to measure the width of the stratum corneum. Sections treated with buffered alkaline solutions were used to expand and count the number of layers of cells in the stratum corneum.

All specimens examined showed evidence of keratinization and, in keeping with previous reports, palatal specimens were more frequently orthokeratinized than gingival specimens. Mean width of the stratum corneum of gingival specimens was approximately 13 μm and of palatal specimens, 23 μm. The mean number of layers of cells in the stratum corneum of the gingiva was approximately 10 and of the palate, approximately 12. Differences in the degree of keratinization and thickness of the stratum corneum between gingival and palatal specimens was statistically significant, but no statistically significant differences were found between the chlorhexidine‐exposed and non‐chlorhexidine‐exposed palatal tissue in keratinization, layers of cells or thickness of the stratum corneum. Neither was there any statistical difference in the same parameters for the gingival specimens. The methods employed did not therefore detect any changes in the normal structure of keratinizing oral epithelia as a result of prolonged daily exposure to chlorhexidine.
Development of plaque on enamel
Authors: Tinanoff Norman , Gross Arthur , Brady John M.
Published: June 2006

Intact human enamel was used to study the development of dental plaque. This procedure involved placing cylinders of surface enamel in an appliance that was worn by one subject up to seven days. By using a technique of slight demineralization of the enamel, pellicle and plaque could be sectioned along with the enamel for light and transmission microscopy. Scanning electron microscopic and microbiologic studies were also performed on the specimens. Microbiologic investigation of two day old samples from the one individual revealed the presence of streptococci and a smaller number of Neisseria. Streptococcus sanguis was the predominant streptococcal species. Early samples of dental plaque appeared to have more desquamated epithelial cells than seven day old plaques. Electron micrographs suggest that bacteria may digest these epithelial cells. An apparent distinction between bacteria adjacent to the enamel and bacteria adsorbed to the surface of the enamel was. noted. Adsorbed bacteria appeared to alter their morphology and excrete an extracellular material which later formed a pellicular layer. Seven day old samples characteristically showed an alignment of rods superior to the adsorbed cocci. The formation of dental plaque on enamel cylinders may better simulate “in vivo” conditions than previous techniques.
Initial gingivitis induced by topical application of plaque extract
Authors: Kahnberg K‐E. , Lindhe J. , Helldén L.
Published: June 2006

The present study was undertaken to examine if soluble substances in human dental plaque were able to induce structural alterations in the marginal gingiva characteristic of initial gingival inflammation.

Four‐day old plaque was sampled from dental students; the plaque material was pooled, suspended in saline, homogenized, centrifuged and filtered. The supernatant, the plaque‐extract, was then, during an eight hour period, topically applied to the gingival margin of the upper jaws of five Beagle dogs. In control regions saline was applied in an identical manner. One and a half hour before sacrifice the animals were given i.v. injections of colloidal carbon.

Biopsies of test and control regions were taken according to a technique described by Schroeder et al (1973). The biopsy specimens were embedded in Epon. Semithin sections (2‐3 μm) were examined in the microscope regarding 1. amount of vascular units subjacent to the junctional epithelium containing carbon particles

2. number of polymorphonuclear and mononuclear leucocytes within the junctional epithelium.

The examinations revealed that the gingival units exposed to plaque extract in comparison to controls harboured larger numbers of carbon labelled vascular units and larger numbers of leukocytes within the junctional epithelium. The data also showed that the main reaction occurred in the marginal portion of the gingival tissue. The observations of this study indicate that soluble substances from human dental plaque when applied topically in the gingival sulcus may give rise to structural alterations similar to those developing in the gingival tissues in response to plaque accumulation.
Salivary IgG and IgA before and after periodontal therapy
Authors: Basu M. K. , Glenwright H. D. , Fox E. C. , Becker J. F.
Published: June 2006

In a study of whole saliva of 12 patients with periodontal disease, IgG concentration was found to be higher and IgA concentration lower, before oral hygiene therapy and periodontal surgery than afterwards. The concentration of these immunoglobulins after periodontal therapy was comparable with those found in clinically normal individuals.
Respiration of bovine gingival epithelium Action of diphenylhydantoin
Authors: Boabaid K. , Brandäo D. , Curial O. , Campello A. P.
Published: June 2006

Biochemical studies on the oxygen uptake by bovine gingival ephitelium slices and mitochondrial fraction were made using the classical manometric technique of Warburg. The integrity of the structure of bovine epithelium mitochondrial fraction was controlled by electron microscopy. The oxygen quotients for bovine gingivai epithelium slices were similar to that reported by others. Only succinate (QO2=1.05) and malate (QO2= 0.89) were oxidized by slices. The mean oxygen quotient endogenous for mitochondrial fraction was 1.46; for succinate and malate were 4.40 and 3.00, respectively. No evident effects of diphenylhydantoin on oxygen consumption either by bovine gingivai epithelium slices or mitochondrial fraction were observed.
Collagens of oral soft tissues
Authors: Schneir M. , Furuto D. , Berger K.
Published: June 2006

The rate of collagen synthesis in rat palatal mucosa decreased markedly from 2.5 to 13 weeks of age when determined by an in vitro labelling technique. Beyond 13 weeks of age, the rate of collagen synthesis remained unchanged and at a relatively low level. These results were not a consequence of isotope‐dilution arising from an increase of tissue collagen mass. For other connective tissues an age‐dependent decrease in net collagen synthesis has been observed and, therefore, is not unique for palatal mucosa. The principal finding of this study was that the rate of conversion of salt‐soluble to salt‐insoluble collagen in palatal mucosa increased with age and remained at a high level in adult rats. In contrast, the rate of conversion of salt‐soluble to ‐insoluble collagen has been reported to decline in adult rat skin. Collectively, the data suggest that collagen in soft oral connective tissues undergoes fibrillogenesis with a rapidity that may be more characteristic of tissues during rapid growth or during healing, rather than tissues during a normal adult stage of metabolism.
Ultrastructure of the dento‐epithelial junction
Authors: Kobayashi Kenichi , Rose George G. , Mahan Charles J.
Published: June 2006

The dento‐epithelial junctions (DEJ) of Rhesus monkeys were examined by electron microscopy. Various fixation procedures were employed in this study. It was revealed that the basal lamina between the junctional epithelium and the tooth surfaces was composed of three layers: the lamina lucida, the lamina densa and the sub‐lamina lucida. Fine filaments often coursed through the lamina densa, lamina lucida and hemidesmosomes and combined them into a structural unit. An electron‐dense linear border, presumably derived from tissue fluid, was generally observed on the tooth surface at the DEJ except that composed of the fibrillar cementum. This border was helpful in distinguishing the afibrillar cementum from the dental cuticle. The existence of a sub‐lamina lucida between the lamina densa and the tooth surfaces is a newly defined layer. It is hypothetically considered to be an area of competetive electrostatic forces of repulsion and London Van der Waals forces of attraction.
Cellular, afibrillar coronal cementum in human teeth
Authors: Silness J. , Gustavsen F. , Fejbrskov O. , Karring T. , Löe H.
Published: June 2006

Mineralized tissue has been observed to be contained in the fissures, of unerupted human third molars. The tissue had morphological features characteristic of afibrillar coronal cementum. In addition, lacunae with canaliculi were contained in the tissue. It is suggested that the tissue is a cellular, afibrillar variety of coronal cementum produced by connective tissue cells which have transformed into cementoblasts after the disappearance of the reduced enamel epithelium from the fissures of the unerupted teeth.
Role of bacterial products in periodontitis
Authors: Johnson David A. , Chen Chen‐Lo H. , Dombrowski John C. , Nowotny Alois
Published: June 2006

Since the two major theories assume that either a hypersensitivity to plaque immunogens or a direct tissue damage caused by plaque constituents plays the dominant role in the etiology of periodontitis, we first investigated the nature of the immune response to and the endotoxin content of human plaque.

It was found that pooled human plaque samples contained a very low but significant level of endotoxin, as determined by phenol‐water extraction, by pyrogenicity in New Zealand white rabbits, by local Shwartzman skin test, and by the Limulus lysate assay.

A measurable humoral immune response could be elicited by human plaque material if injected into guinea pigs intraperitoneally. Intragingival application of the same material was a less efficient route of immunization. This humoral immune response was measured by passive hemagglutination and immune counterelectrophoresis.

Cell‐mediated immune response, as measured by skin sensitivity, lymphoblast transformation and rosette formation assays in guinea pigs, sensitized either intragingivally or intraperitoneally, gave diverse results. No cell‐mediated immune response could be detected by using the lymphoblast transformation assay. A weak but positive reaction could be elicited in one‐third to one‐half of the sensitized animals by injecting them intradermally or by testing rosette formation of their spleen cells with plaque‐coated sheep erythrocytes.

The weak and inconsistent results do not rule out the possibility that cell‐mediated immune responses and their mediators cause human periodontitis, but they make us cautious in considering such events as the sole factors in the development of the disease. As of now, we have even less reason to exclude the possibility that certain types of immune responses to plaque protect the patient from periodontitis.
The biomechanical effects of simulated osseous surgery
Authors: Ian Vogan W. , Knoell A. C.
Published: June 2006

Using dried human mandibles, to which miniaturised strain gauges were attached, the strain in the buccal alveolar plate, under horizontal and vertical loading conditions was measured. Recordings were repeated after simulated infra‐bony defects had been created and again after simulated osteoplasty and osteoectomy had been carried out to eliminate the osseous defects. The results indicate that in the dried mandibles, osseous surgery procedures resulted in measurable increases in strain in the bone overlying those teeth involved with the lesion and subsequent osseous surgery. In addition, there was a greater concentration of strain in the region of these teeth when they were loaded after simulated osseous surgery. Although the quantitative effects of “osteoectomy” were greater than those of “osteoplasty”, the latter procedure, currently defined as the removal of “nonsupporting” bone, did in fact result in sizeable changes in the strain dissipation of the system.
Hierarchical subfunctionalization of fabp1a, fabp1b and fabp10 tissue‐specific expression may account for retention of these duplicated genes in the zebrafish (Danio rerio) genome
Authors: Sharma Mukesh K. , Liu Rong‐Zong , Thisse Christine , Thisse Bernard , Denovan‐Wright Eileen M. , Wright Jonathan M.
Published: June 2006

Fatty acid‐binding protein type 1 (FABP1), commonly termed liver‐type fatty acid‐binding protein (L‐FABP), is encoded by a single gene in mammals. We cloned and sequenced cDNAs for two distinct FABP1s in zebrafish coded by genes designated fabp1a and fabp1b. The zebrafish proteins, FABP1a and FABP1b, show highest sequence identity and similarity to the human protein FABP1. Zebrafish fabp1a and fabp1b genes were assigned to linkage groups 5 and 8, respectively. Both linkage groups show conserved syntenies to a segment of mouse chromosome 6, rat chromosome 4 and human chromosome 2 harboring the FABP1 locus. Phylogenetic analysis further suggests that zebrafish fabp1a and fabp1b genes are orthologs of mammalian FABP1 and most likely arose by a whole‐genome duplication event in the ray‐finned fish lineage, estimated to have occurred 200–450 million years ago. The paralogous fabp10 gene encoding basic L‐FABP, found to date in only nonmammalian vertebrates, was assigned to zebrafish linkage group 16. RT‐PCR amplification of mRNA in adults, and in situ hybridization to whole‐mount embryos to fabp1a, fabp1b and fapb10 mRNAs, revealed a distinct and differential pattern of expression for the fabp1a, fabp1b and fabp10 genes in zebrafish, suggesting a division of function for these orthogolous and paralogous gene products following their duplication in the vertebrate genome. The differential and complementary expression patterns of the zebrafish fabp1a, fapb1b and fabp10 genes imply a hierarchical subfunctionalization that may account for the retention of both the duplicated fabp1a and fabp1b genes, and the fabp10 gene in the zebrafish genome.
Identification, subcellular localization and functional interactions of PilMNOWQ and PilA4 involved in transformation competency and pilus biogenesis in the thermophilic bacterium Thermus thermophilus HB27
Authors: Rumszauer Judit , Schwarzenlander Cornelia , Averhoff Beate
Published: June 2006

The natural transformation system of the thermophilic bacterium Thermus thermophilus HB27 comprises at least 16 distinct competence proteins encoded by seven distinct loci. In this article, we present for the first time biochemical analyses of the Thermus thermophilus competence proteins PilMNOWQ and PilA4, and demonstrate that the pilMNOWQ genes are each essential for natural transformation. We identified three different forms of PilA4, one with an apparent molecular mass of 14 kDa, which correlates with that of the deduced protein, an 18‐kDa form and a 23‐kDa form; the last was found to be glycosylated. We demonstrate that PilM, PilN and PilO are located in the inner membrane, whereas PilW, PilQ and PilA4 are located in the inner and outer membranes. These data show that PilMNOWQ and PilA4 are components of a DNA translocator structure that spans the inner and outer membranes. We further show that PilA4 and PilQ both copurify with pilus structures. Possible functions of PilQ and PilA4 in DNA translocation and in pilus biogenesis are discussed. Comparative mutant studies revealed that mutations in either pilW or pilQ significantly affect the location of the other protein in the outer membrane. Furthermore, no PilA4 was present in the outer membranes of these mutants. From these findings, we conclude that the abilities of PilW, PilQ and PilA4 to stably localize or accumulate in the outer membrane fraction are strongly dependent on one another, which is in accord with an outer membrane DNA translocator complex comprising PilW, PilQ, and PilA4.
The epigenetic magic of histone lysine methylation
Authors: Jenuwein Thomas
Published: June 2006

Epigenetic mechanisms control eukaryotic development beyond DNA‐stored information. There are several pathways, including histone tail modifications, histone variant incorporation, nucleosome remodelling, DNA methylation and noncoding RNAs that together all contribute to the dynamic ‘make‐up’ of chromatin under distinct developmental options. The histone tail modifications are most variable and over 50 marks have by now been mapped. While the majority of these modifications are transient, histone lysine methylation and, in particular, a histone lysine tri‐methyl state has been regarded as a more robust signal, consistent with proposed roles to impart long‐term epigenetic memory. Based on the paradigm of SET‐domain histone lysine methyltransferases (HMTases) and chromo‐domain adaptor proteins, and in conjunction with the Sir Hans Krebs Medal 2005, I describe here my personal view on the discovery of the first HMTase in 2000, and the subsequent advances on the biology of histone lysine methylation. This discovery has changed my scientific career and significantly contributed to a better understanding of epigenetic control, with important implications for heterochromatin formation, X inactivation, Polycomb group silencing and novel insights into stem cell research, nuclear reprogramming and cancer.
Kinematic structure in the young σ Orionis association
Authors: Jeffries R. D. , Maxted P. F. L. , Oliveira J. M. , Naylor Tim
Published: June 2006

We have used precise radial velocity measurements for a large number of candidate low-mass stars and brown dwarfs to show that the young σ Ori ‘cluster’ consists of two spatially superimposed components which are kinematically separated by 7 km s−1 in radial velocity, and which have different mean ages. We examine the relationship of these two kinematic groups to other populations in the Orion OB1 association, and briefly discuss the consequence of mixed age samples for ongoing investigations of the formation and evolution of low-mass objects in this much-observed region.
Canals in Milky Way radio polarization maps
Authors: Fletcher A. , Shukurov A.
Published: June 2006

Narrow depolarized canals are common in maps of the polarized synchrotron emission of the Milky Way. Two physical effects that can produce these canals have been identified: the presence of Faraday rotation measure (RM) gradients in a foreground screen, and the cumulative cancellation of polarization known as differential Faraday rotation. We show that the behaviour of the Stokes parameters Q and U in the vicinity of a canal can be used to identify its origin. In the case of canals produced by a Faraday screen we demonstrate that, if the polarization angle changes by 90° across the canal, as is observed in all fields to-date, the gradients in RM must be discontinuous. Shocks are an obvious source of such discontinuities and we derive a relation of the expected mean separation of canals to the abundance and Mach number of supernova-driven shocks, and compare this with recent observations by Haverkorn, Katgert & de Bruyn. We also predict the existence of less common canals with polarization angle changes other than 90°. Differential Faraday rotation can produce canals in a uniform magneto-ionic medium, but as the emitting layer becomes less uniform the canals will disappear. We show that for moderate differences in emissivity in a two-layer medium, of up to 1/2, and for Faraday depth fluctuations of standard deviation ≲1 rad, canals produced by differential rotation will still be visible.
Vagal nerve activity contributes to improve the efficiency of pulmonary gas exchange in hypoxic humans
Authors: Ito Shoji , Sasano Hiroshi , Sasano Nobuko , Hayano Junichiro , Fisher Joseph A. , Katsuya Hirotada
Published: June 2006

The aim of this study was to test our hypothesis that both phasic cardiac vagal activity and tonic pulmonary vagal activity, estimated as respiratory sinus arrhythmia (RSA) and anatomical dead space volume, respectively, contribute to improve the efficiency of pulmonary gas exchange in humans. We examined the effect of blocking vagal nerve activity with atropine on pulmonary gas exchange. Ten healthy volunteers inhaled hypoxic gas with constant tidal volume and respiratory frequency through a respiratory circuit with a respiratory analyser. Arterial partial pressure of O2 (P) and arterial oxygen saturation (S) were measured, and alveolar‐to‐arterial P difference (D) was calculated. Anatomical dead space (VD,an), alveolar dead space (VD,alv) and the ratio of physiological dead space to tidal volume (VD,phys/VT) were measured. Electrocardiogram was recorded, and the amplitude of R–R interval variability in the high‐frequency component (RRIHF) was utilized as an index of RSA magnitude. These parameters of pulmonary function were measured before and after administration of atropine (0.02 mg kg−1). Decreased RRIHF (P < 0.01) was accompanied by decreases in P and S (P < 0.05 and P < 0.01, respectively) and an increase in D (P < 0.05). Anatomical dead space, VD,alv and VD,phys/VT increased (P < 0.01, P < 0.05 and P < 0.01, respectively) after atropine administration. The blockade of the vagal nerve with atropine resulted in an increase in VD,an and VD,alv and a deterioration of pulmonary oxygenation, accompanied by attenuation of RSA. Our findings suggest that both phasic cardiac and tonic pulmonary vagal nerve activity contribute to improve the efficiency of pulmonary gas exchange in hypoxic conscious humans.
Low cell pH depresses peak power in rat skeletal muscle fibres at both 30°C and 15°C: implications for muscle fatigue
Authors: Knuth S. T. , Dave H. , Peters J. R. , Fitts R. H.
Published: June 2006

Historically, an increase in intracellular H+ (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross‐bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H+ as a fatigue agent has been questioned. The purpose of this work was to re‐evaluate the role of H+ in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast‐ and slow‐twitch muscle fibres at 15°C and 30°C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15°C and 30°C and pH 7.0 and 6.2, and fibre force (P0), unloaded shortening velocity (V0), force–velocity, and force–power relationships determined. Consistent with previous observations, low pH depressed the P0 of both fast and slow fibres, less at 30°C (4–12%) than at 15°C (30%). However, the low pH‐induced depressions in slow type I fibre V0 and peak power were both significantly greater at 30°C (25%versus 9% for V0 and 34%versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V0 was unaltered by temperature, while for peak power the inhibition was reduced at 30°C (37%versus 18%). The curvature of the force–velocity relationship was temperature sensitive, and showed a higher a/P0 ratio (less curvature) at 30°C. Importantly, at 30°C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow‐ and fast‐twitch fibres at near‐in vivo temperatures (30°C) is greater than would be predicted based on changes in P0, and that the fatigue‐inducing effects of low pH on cross‐bridge function are still substantial and important at temperatures approaching those observed in vivo.
Physiological roles for amyloid β peptides
Authors: Pearson Hugh A. , Peers Chris
Published: June 2006

Alzheimer's disease is recognized post mortem by the presence of extracellular senile plaques, made primarily of aggregation of amyloid β peptide (Aβ). This peptide has consequently been regarded as the principal toxic factor in the neurodegeneration of Alzheimer's disease. As such, intense research effort has been directed at determining its source, activity and fate, primarily with a view to preventing its formation or its biological activity, or promoting its degradation. Clearly, much progress has been made concerning its formation by proteolytic processing of the amyloid precursor protein, and its degradation by enzymes such as neprilysin and insulin degrading enzyme. The activities of Aβ, however, are numerous and yet to be fully elucidated. What is currently emerging from such studies is a diffuse but steadily growing body of data that suggests Aβ has important physiological functions and, further, that it should only be regarded as toxic when its production and degradation are imbalanced. Here, we review these data and suggest that physiological levels of Aβ have important physiological roles, and may even be crucial for neuronal cell survival. Thus, the view of Aβ being a purely toxic peptide requires re‐evaluation.
Microarrays and the microscope: balancing throughput with resolution
Authors: Coppola Giovanni , Geschwind Daniel H.
Published: June 2006

The cellular complexity of the brain is a major issue in the planning, execution and interpretation of microarray studies. Recent technical advances allow for high‐throughput study of specific cell populations and circuits. Here we review representative examples of currently available methods that allow high resolution and specificity in brain microarray studies, while maintaining the goal of comprehensive, high‐throughput analysis.
Vestibular inputs elicit patterned changes in limb blood flow in conscious cats
Authors: Wilson T. D. , Cotter L. A. , Draper J. A. , Misra S. P. , Rice C. D. , Cass S. P. , Yates B. J.
Published: June 2006

Previous experiments have demonstrated that the vestibular system contributes to regulating sympathetic nervous system activity, particularly the discharges of vasoconstrictor fibres. In the present study, we examined the physiological significance of vestibulosympathetic responses by comparing blood flow and vascular resistance in the forelimb and hindlimb during head‐up tilt from the prone position before and after the removal of vestibular inputs through a bilateral vestibular neurectomy. Experiments were performed on conscious cats that were trained to remain sedentary on a tilt table during rotations up to 60 deg in amplitude. Blood flow through the femoral and brachial arteries was recorded during whole‐body tilt using perivascular probes; blood pressure was recorded using a telemetry system and vascular resistance was calculated from blood pressure and blood flow measurements. In vestibular‐intact animals, 60 deg head‐up tilt produced ∼20% decrease in femoral blood flow and ∼37% increase in femoral vascular resistance relative to baseline levels before tilt; similar effects were also observed for the brachial artery (∼25% decrease in blood flow and ∼38% increase in resistance). Following the removal of vestibular inputs, brachial blood flow and vascular resistance during head‐up tilt were almost unchanged. In contrast, femoral vascular resistance increased only ∼6% from baseline during 60 deg head‐up rotation delivered in the first week after elimination of vestibular signals and ∼16% in the subsequent 3‐week period (as opposed to the ∼37% increase in resistance that occurred before lesion). These data demonstrate that vestibular inputs associated with postural alterations elicit regionally specific increases in vascular resistance that direct blood flow away from the region of the body where blood pooling may occur. Thus, the data support the hypothesis that vestibular influences on the cardiovascular system serve to protect against the occurrence of orthostatic hypotension.
Modulation of calcium wave propagation in the dendrites and to the soma of rat hippocampal pyramidal neurons
Authors: Watanabe Shigeo , Hong Min , Lasser‐Ross Nechama , Ross William N.
Published: June 2006

Repetitive synaptic stimulation in the stratum radiatum (SR) evokes large amplitude Ca2+ waves in the thick apical dendrites of hippocampal CA1 pyramidal neurons. These waves are initiated by activation of metabotropic glutamate receptors (mGluRs), which mobilize inositol‐1,4,5‐trisphospate (IP3) and release Ca2+ from intracellular stores. We explored mechanisms that modulate the spatial properties of these waves. Higher stimulus current evoked waves of increasing spatial extent. Most waves did not propagate through the soma; the majority stopped close to the junction of the soma and apical dendrite. Pairing strong stimulation with one electrode and subthreshold stimulation with another (associative activation) extended the waves distally but failed to extend waves into the cell body. Pairing synaptic stimulation with backpropagating action potentials enhanced the likelihood of wave generation but did not extend the waves to the somatic region. Priming the stores with Ca2+ entry through voltage dependent channels modulated wave properties but did not extend them past the dendrites. These results are consistent with propagation failing due to the dilution of synaptically generated IP3 as it diffuses into the large volume of the soma (impedance mismatch). Synaptically activating waves in the presence of low concentrations of carbachol, which probably increased the tonic level of IP3 throughout the cell, enhanced the extent of propagation and generated waves that invaded the soma, as long as low‐affinity indicators were used to detect the [Ca2+]i changes. Consistent with this explanation direct injection of IP3 into the soma promoted wave propagation into this region. Ca2+ waves that propagated through the cell body were interesting because they did not fill the volume of the soma, but passed through the centre, often with large amplitude. These waves may be particularly effective in activating gene expression and protein synthesis.
Long‐term intermittent hypoxia increases sympathetic activity and chemosensitivity during acute hypoxia in humans
Authors: Lusina Sarah‐Jane C. , Kennedy Paul M. , Inglis J. Timothy , McKenzie Donald C. , Ayas Najib T. , Sheel A. William
Published: June 2006

We determined the effects of 10 daily exposures of intermittent hypoxia (IH; 1 h day−1; oxyhaemoglobin saturation = 80%) on muscle sympathetic nerve activity (MSNA, peroneal nerve) and the hypoxic ventilatory response (HVR) before, during and after an acute 20 min isocapnic hypoxic exposure. We also assessed the potential parallel modulation of the ventilatory and sympathetic systems following IH. Healthy young men (n= 11; 25 ± 1 years) served as subjects and pre‐ and post‐IH measures of MSNA were obtained on six subjects. The IH intervention caused HVR to significantly increase (pre‐IH = 0.30 ± 0.03; post‐IH = 0.61 ± 0.12 l min−1%S−1). During the 20 min hypoxic exposure sympathetic activity was significantly greater than baseline and remained above baseline after withdrawal of the hypoxic stimulus, even though oxyhaemoglobin saturation had normalized and ventilation and blood pressure had returned to baseline levels. When compared to the pre‐IH trial, burst frequency increased (P < 0.01), total MSNA trended towards higher values (P= 0.06), and there was no effect on burst amplitude (P= 0.82) during the post‐IH trial. Following IH the rise in MSNA burst frequency was strongly related to the change in HVR (r= 0.79, P < 0.05) suggesting that these sympathetic and ventilatory responses may have common central control.
GABAA receptor subtype specific enhancement of inhibition in human motor cortex
Authors: Di Lazzaro Vincenzo , Pilato Fabio , Dileone Michele , Ranieri Federico , Ricci Valerio , Profice Paolo , Bria Pietro , Tonali Pietro A. , Ziemann Ulf
Published: June 2006

Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and γ‐aminobutyric acid A receptor (GABAAR) subtypes. Here we employed paired‐pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABAAR‐mediated inhibition in human motor cortex, to address the question of which GABAAR subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non‐selective affinity profile at different α‐subunit‐bearing subtypes of the GABAAR while zolpidem has a 10‐fold greater affinity to the α1‐subunit‐bearing GABAAR compared with those bearing the α2‐ or α3‐subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an α1‐subunit GABAAR‐mediated effect. The findings strongly suggest that SICI is not mediated by the α1‐subunit‐bearing subtype of the GABAAR but by those bearing either the α2‐ or α3‐subunit. This study represents an attempt by means of TMS to identify GABAAR subtype‐specific action at the systems level of human cortex, a highly relevant issue because the different α‐subunit‐bearing subtypes of the GABAAR are differently involved in benzodiazepine‐mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.
Contraction‐initiated NO‐dependent lymphatic relaxation: a self‐regulatory mechanism in rat thoracic duct
Authors: Gasheva Olga Yu. , Zawieja David C. , Gashev Anatoliy A.
Published: June 2006

The objectives of this study were to evaluate the physiological importance of the flow and shear generated by phasic contractions of lymphatic vessels and the mechanisms responsible for the influences of such shear on lymphatic pumping. Lymphatic segments of the rat thoracic duct were isolated, cannulated and pressurized. The diastolic diameters were measured in phasically non‐active segments. The diastolic and systolic diameters, half‐relaxation time (HRT), contraction frequency, ejection fraction and fractional pump flow were determined in phasically active segments. Since imposed flow was excluded, flow and shear occurred only as a result of the intrinsic contractions in phasically active segments whereas in phasically non‐active segments contraction‐generated flow and shear were absent. The influences of incrementally increased transmural pressure (from 1 to 5 cmH2O) were examined in control conditions and after NO synthase blockade (l‐NAME 10−4m) or cyclooxygenase blockade (indomethacin 10−5m). The spontaneous phasic contractions produced a flow‐dependent diastolic relaxation. This reduction of the lymphatic tone is a regulatory mechanism that maintains pumping in thoracic duct in an energy‐saving/efficient mode: it improves diastolic filling (enhanced lusitropy – lowering HRT), makes lymphatic contractions stronger (enhanced inotropy – higher contraction amplitude) and propels more fluid forward during each contraction (elevated ejection fraction) while decreasing contraction frequency (reduced chronotropy). The findings also demonstrated that the NO pathway, not the cyclooxygenase pathway is responsible for this reduction of lymphatic tone and is the prevailing pathway responsible for the self‐regulatory adjustment of thoracic duct pumping to changes in lymph flow pattern.
Actual Safety Distance and Winding Tension to Manufacture Full Section Parts by Robotized Filament Winding
Authors: Polini W. , Sorrentino L.
Published: June 2006

Robotized filament winding technology allows one to manufacture workpieces of high performances as a result of a robot placing fibers impregnated by resin (known as roving) along the directions of stresses the workpiece is subjected to in exercise; thus, robotized filament winding favors rigidity and strength of a workpiece along some preferential directions. A proper value of the winding tension has to be chosen and kept constant along the whole winding in order to limit the defects inside the composite workpieces. To keep the tension value on roving near to the nominal value, one must plan the value of the geometric parameters characterizing the winding trajectory. The same geometric parameters influence the value of the actual safety distance that may involve collisions among the deposition system and the components of the robotized cell. This work shows how to avoid the occurrence of collisions by planning the value of the actual safety distance through the definition of geometric parameters that characterize the winding trajectory. Moreover, the collision occurrence should be considered together with the control of the winding tension on the roving in the robotized filament winding planning stage. The present work shows how to solve both the problems previously defined (i.e., to keep the winding tension on roving near to the nominal value and to avoid collision occurrence), by the solution of a constrained optimization system.
Measurement and Prediction of the Residual Stress Field Generated by Side-Punching
Authors: Mahmoudi A. H. , Stefanescu D. , Hossain S. , Truman C. E. , Smith D. J. , Withers P. J.
Published: June 2006

Side-punching is proposed as a method of introducing a well-defined residual stress field into a laboratory-sized test specimen. Such a specimen may subsequently be used to assess the influence of residual stresses on the fracture behavior of materials. Side-punching consists of simultaneously indenting opposite faces of a plate of material with rigid tools, using sufficient force to cause localized yielding over a finite-sized volume of material adjacent to the punching tools. This paper presents experimental measurements, obtained using three independent measurement techniques, of the residual stress field generated in an aluminium alloy plate after side-punching. Incremental center hole drilling is used to determine the near-surface residual stress field, while synchrotron x-ray diffraction and deep hole drilling are used to measure the through-thickness residual stress field along a path linking the two punch center points. Finite element (FE) predictions are also presented and compared to the measurements. There is very good agreement between all three sets of measurements and the FE results, which all show that the through-thickness residual stresses are compressive and attain a maximum value at the center of the plate. The results confirm the potential use of side-punching in residual stress-crack interaction studies.