bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Type 2 Cytokines on Glomerular Epithelial Cells
Authors: Parry Robin G. , Gillespie Kathleen M. , Mathieson Peter W.
Published: April 2003

Visceral glomerular epithelial cells (GECs) are involved in the maintenance of the filtration barrier and may play a role in immune responses. Cytokines may act on GECs and we wished to test this in vitro. Vascular endothelial growth factor (VEGF) is a specific product of the GEC that may play a role in glomerular permeability. We have investigated whether GECs in culture express receptors for interleukin (IL)-4, 10 and 13 (often grouped together as type 2 cytokines) and whether these cytokines alter GEC VEGF production. Type 2 cytokines were compared to transforming growth factor-β (TGF-β) and IL-1β which are known to upregulate VEGF production. GECs were grown from human nephrectomy specimens and cultured with and without the addition of exogenous cytokines. Messenger RNA data demonstrated the presence of IL-4 receptor α, IL-10 receptor 1 and 2, and IL-13 receptors α1 and α2. However, at the protein level by flow cytometry, only IL-13 α2 could be consistently demonstrated. IL-4, IL-10 and IL-13 inhibited production of VEGF but did not affect the pattern of isoform expression. In contrast, TBF-β and IL-1β caused an increase in VEGF production. These effects were not explained by effects on proliferation. Our data provide evidence that GECs express receptors for type 2 cytokines and that these cytokines can act directly on GECs, to decrease VEGF production.
Endothelin and Endothelin A/B Receptors Are Increased after Ischaemic Acute Renal Failure
Authors: Forbes Josephine M. , Jandeleit-Dahm Karin , Allen Terri J. , Hewitson Tim D. , Becker Gavin J. , Jones Colin L.
Published: April 2003

Background/Aims: Endothelin (ET) has been implicated as an indirect mediator of injury following acute renal ischaemia (ARI). The purpose of this study was to localize and quantitate ET and ETA and ETB receptors following ARI. Methods: A model of ARI, well characterized previously, was produced by 45 min occlusion of the renal pedicle of unilaterally nephrectomized female Sprague-Dawley rats. Animals were sacrificed 1, 2, 4, 8, 16, 32 and 64 days after ischaemia (n = 6). Corresponding control groups with unilateral nephrectomy but no ischaemia were sacrificed after 0, 8 and 64 days. Immunohistochemistry for ET-1, -2 and -3 was performed. Tissue ET levels were calculated by RIA (femtomoles per kidney). Receptor ligand binding studies for ETA and ETB receptors were performed by autoradiography on frozen kidney sections and quantitated by densitometry (relative optical density per square millimetre). Results: The concentration of tissue ET increased from 24 h after ischaemia and remained significantly increased for the duration of the study, reaching a maximum at 8 days. There was a small increase in the non-ischaemic 8-day control group, but this returned to basal levels by day 64. The increase in tissue ET 8 days after ischaemia was localized by immunohistochemistry to renal medullary interstitial cells, damaged tubules at the corticomedullary junction and peritubular capillaries surrounding these damaged tubules. Increases in cortical ETA and ETB receptors were evident 24 h after ischaemia and were maximal 8 days after ischaemia, before returning to basal levels at 16 days. After a small increase 24 h after ischaemia, medullary ETA receptors decreased on day 4 before returning to basal levels on day 8 after ischaemia. Medullary ETB receptors, however, decreased on day 4 after ischaemia and remained low throughout the duration of the study. Conclusion: The previously reported amelioration of pathological changes resulting from the use of ET receptor antagonists after ARI may be related to the quantitative and qualitative changes in tissue ET and ET receptors observed in this study.
Recurrence of Nephrotic Syndrome after Transplantation in CNF Is due to Autoantibodies to Nephrin
Authors: Wang Shi-Xuan , Ahola Heikki , Palmen Tuula , Solin Marja-Liisa , Luimula Pauliina , Holthöfer Harry
Published: April 2003

The novel gene NPHS1 is defective in the patients with congenital nephrotic syndrome of the Finnish type (CNF) leading to abnormal expression of the respective protein product nephrin in glomerular cells. CNF patients are treated with early nephrectomy and renal transplantation, but about 20% show recurrence of nephrotic syndrome (NS). We used indirect immunofluorescence microscopy and immunoblotting and an ELISA assay to search for circulating autoantibodies to nephrin, the protein defect in CNF patient kidneys. In serial serum samples gathered before and after recurrence of NS, we show an increased antibody titer to nephrin prior to the NS episode and a subsequent drop in antibody level after its successful treatment and reactivity of the high titer sera with glomeruli in indirect immunofluorescence microscopy as well. The results show that the transplantation treatment introduces a neoantigen inducing production of autoantibodies, which may be pathogenic for perturbation of the function of the glomerular filtration barrier.
Unraveling the Molecular Make-Up of the Glomerular Podocyte Slit Diaphragm
Authors: Khoshnoodi Jamshid , Tryggvason Karl
Published: April 2003

Recent discoveries in podocyte proteins involved in the renal filtration barrier have shed new light on the ultrastructure of the kidney filter and pathogenesis of proteinuria. The identification of nephrin, a component of the slit diaphragm, and the intracellular slit diaphragm associated proteins CD2AP and podocin has demonstrated the existence of proteins that directly contribute to a functional kidney filter. Mutations in the genes for these three proteins result in proteinuria and nephrotic syndrome, and these proteins are also likely to be involved more generally in the pathomechanisms of proteinuria. This new knowledge has been promoted particularly through the powerful methods of molecular genetics and molecular biology. In this minireview, we present the recent progress in research of the podocyte slit diaphragm.
Apoptosis Induced by Serum Withdrawal in Human Mesangial Cells
Authors: Verzola Daniela , Villaggio Barbara , Berruti Valeria , Gandolfo Maria Teresa , Deferrari Giacomo , Garibotto Giacomo
Published: April 2003

Apoptosis has been reported to occur both during the course of kidney development and the progression of kidney injury to scarring. Insulin-like growth factor binding protein-3 (IGFBP-3), a component of the IGF system, has been shown to induce apoptosis in cancer cell lines. However, if IGFBP-3 has similar effects in human mesangial cells (HMC) remains unknown. The purpose of this study was to examine the expression of IGFBP-3 and its possible effect on the induction of apoptosis in HMC during serum deprivation. We have observed that IGFBP-3 accumulates progressively in HMC in which serum has been withdrawn. In these cells, an increase of IGFBP-3 is observed before the production of apoptosis suggesting a link between these phenomena. Furthermore, the addition of IGFBP-3 in physiological amounts (from 100 to 400 ng/ml) to culture medium devoid of growth factors accelerates and increases the apoptotic process with a dose-dependent effect. These findings suggest that IGFBP-3 is a mediator of cell death in human mesangial cells when the availability of growth factors is curtailed. These data also suggest that IGFBP-3 could contribute to apoptotic processes observed in human disease.
Increased Expression of Glutathione S- Transferase in Renal Proximal Tubules in the Early Stages of Diabetes: A Study of Type-2 Diabetes in the Akita Mouse Model
Authors: Fujita Hiroki , Haseyama Toshiyuki , Kayo Tsuyoshi , Nozaki Jun-ichi , Wada Yasuhiko , Ito Seiki , Koizumi Akio
Published: April 2003

Background/Aim: The objective of this study was to examine whether the gene expression profile in the kidney is modified by hyperglycemia in the early stage of diabetes. Methods: We analyzed the expression of kidney mRNAs using cDNA array membranes including 588 genes in the kidney of the Akita mouse, a model of type-2 diabetes, after exposure to hyperglycemia for a moderate length of time, but before the manifestation of diabetic glomerulosclerosis. Western blot analysis and immunohistochemical studies were performed to confirm whether the protein for the increasingly expressed mRNA was highly expressed in the kidney of the diabetic mouse. Results: Two of the 10 detected mRNAs, glutathione S-transferase (GST) α and µ, in the kidneys from diabetic mice showed a more than twofold increased expression in comparison to those of control mice. Western blot analysis in kidney tissue extracts confirmed increases in GST α and µ at protein levels in the diabetic mice. Immunohistochemical studies revealed strong staining for those proteins in the proximal tubules of diabetic mice. Conclusion: These data collectively indicate that expression of GSTs is increased in epithelial cells in proximal tubules even at the early stage of diabetes, probably in response to oxidative stress triggered by hyperglycemia or other toxic effects of glucose.
Renal Effects of Nabumetone, a COX-2 Antagonist: Impairment of Function in Isolated Perfused Rat Kidneys Contrasts with Preserved Renal Function in vivo
Authors: Reichman James , Cohen Shlomo , Goldfarb Marina , Shina Ahuva , Rosen Seymour , Brezis Mayer , Karmeli Fanny , Heyman Samuel N.
Published: April 2003

The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the ‘inducible’ isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10–20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.
Evidence for a Sorbitol Transport System in Immortalized Human Renal Interstitial Cells
Authors: Grunewald Rolf Willi , Ehrhard Martin , Fiedler Georg Martin , Schüttert Jan Bernd , Oppermann Mona , Müller Gerhard Anton
Published: April 2003

Sorbitol plays a major role in the maintenance of cell volume and functional integrity of several renal cells. Sorbitol synthesis takes place in inner collecting duct cells, whereas sorbitol dehydrogenase activity, which catalyzes the degradation of sorbiotol to fructose, could mainly be detected in renal inner medullary interstitial cells. Therefore, we supposed that interstitial cells would require a sorbitol transport into the cells. However, such a transport system has not yet been described. Therefore, we have characterized the uptake of sorbitol in immortalized interstitial TK-173 cells, which were derived from human renal fibroblasts. Comparable to fresh isolated renal fibroblasts of the rat, immortalized TK-173 cells have a high sorbitol dehydrogenase activity. In this report, a temperature-dependent sorbitol uptake with saturation kinetics could be detected in immortalized TK-173 cells. The transport is characterized by a high velocity (Vmax 84 mmol/l × h) and an apparent Km of 10 mmol/l. The sorbitol uptake is independent of membrane potential, sodium, and chloride. Altogether, the physiological characteristics of this sorbitol transport are different from those of the osmotically regulated sorbitol efflux from epithelial cells. These results provide evidence that TK-173 cells derived from renal fibroblasts have a specific sorbitol transport. Furthermore, these data suggest a cooperation between epithelial and interstitial cells concerning osmoregulation.
Protein Localization and mRNA Expression of Epimorphin in Mouse and Human Kidneys
Authors: Horikoshi Satoshi , Yoshikawa Mutsuko , Shibata Terumi , Takahashi Kaoru , Shirato Isao , Tomino Yasuhiko
Published: April 2003

Epimorphin is a mesenchymal cell surface protein which induces epithelial branching morphogenesis. However, the role of epimorphin in the kidney has not been addressed. In the present study, the localization of epimorphin protein and the expression of its mRNA were investigated in the developing mouse and adult human kidneys using immunohistochemistry and semiquantitative RT-PCR. The in vitro expression of epimorphin protein and its mRNA was also explored in cultured mouse and human mesangial cells. Epimorphin protein was expressed in the renal interstitium and the circumference of the comma-shaped body at day 16 of gestation. The intensity and distribution of epimorphin were gradually increased during kidney differentiation and maturation. Epimorphin was first observed in glomeruli at 1 week of age. The localization of epimorphin in glomerular mesangial cells and interstitial fibroblasts was confirmed by immunoelectron microscopy of 2-week-old mouse kidneys. The highest mRNA expression of epimorphin was observed at day 16 of gestation, thereafter it diminished with the maturation of the kidney. A similar localization of epimorphin was observed in a normal adult human kidney. Cultured human mesangial cells expressed epimorphin mRNA 150-kD protein. These results suggest that epimorphin may play a role in the development of the kidney and in the differentiation of fibroblast and mesangial cells.
Altered Cultured Mesangial Cell Phenotypes from RF/J Mice: A Spontaneous Immune Complex Mediated Glomerulonephritis with Progressive Glomerulosclerosis
Authors: Yashiro Masatomo , Muso Eri , Kamata Tadashi , Oyama Atsushi , Sasayama Shigetake , Yoshida Haruyoshi
Published: April 2003

Background/Aim: RF/J mice are a model of spontaneous immune complex mediated glomerulonephritis showing massive extracellular matrix accumulation and progressive glomerulosclerosis. The aim of this study was to investigate whether there is an altered cultured mesangial cell (MC) phenotype in RF/J mice associated with these glomerular changes. Methods: The nature of cultured MCs from RF/J mice in the proliferative response to platelet-derived growth factor (PDGF) BB was compared with that of normal mice (BALB/c) by 3H-thymidine incorporation. The binding of PDGF-BB was examined with Scatchard analysis, and the messenger RNAs (mRNAs) of PDGF β-receptor, collagen I, collagen IV, and fibronectin were detected using Northern blot analysis in the MCs of each mouse. Results: The 3H-thymidine incorporation of MCs from RF/J mice showed significantly lower responses to PDGF-BB stimulations with concentrations ranging from 0.5 to 10.0 ng/ml in comparison with those of BALB/c mice which exhibited a proportional dose- dependent increase of the incorporation (p < 0.05 for 0.5 ng/ml PDGF-BB, p < 0.01 for 1.0–10.0 ng/ml). According to the Scatchard analysis, MCs from BALB/c mice showed aKD of 105 pM of PDGF-BB binding to its receptors, and the density of receptors was 5.82 fmol/105 cells. However, no binding PDGF-BB site on the surface of MCs from RF/J mice was noted. Northern blot analysis of MCs from RF/J mice indicated negative expression of detectable PDGF-β receptor mRNA. As for matrix protein messages, MCs from RF/J mice did not express mRNA of type I collagen, but did express a higher amount of type IV collagen and fibronectin in comparison with MCs from normal BALB/c mice. Conclusions: An altered phenotype in MCs of RF/J mice was demonstrated, possibly contributing to the characteristic pathological glomerular changes. However, the precise association remains to be clarified.
Expression and Signaling of Parathyroid Hormone-Related Protein in Cultured Podocytes
Authors: Endlich Nicole , Nobiling Rainer , Kriz Wilhelm , Endlich Karlhans
Published: April 2003

Podocyte function appears to be regulated by vasoactive factors. In vivo podocytes express parathyroid hormone-related protein (PTHrP), the N-terminal fragment of which has vasoactive properties. Since the signaling pathway(s) of PTHrP(1–36) are unknown in podocytes, differentiated cells of a conditionally immortalized mouse podocyte cell line were studied. Gene expression of PTHrP and the PTH/PTHrP receptor was investigated by RT-PCR; protein distribution of PTHrP was examined by immunofluorescence. Accumulation of cAMP was determined by an enzyme immunoassay; [Ca2+]i was measured by fura-2 ratio imaging. PTHrP and PTH/PTHrP receptor mRNA was detected in differentiated podocytes. Immunoreactive PTHrP exhibited a granular distribution in the cytoplasm of differentiated podocytes. With regard to the signaling pathway(s) of PTHrP(1–36), a concentration-dependent increase of cAMP levels with an EC50 value of 4 ± 2 nM was found. PTHrP(1–36) (1 µM) increased cAMP levels 5.5 ± 1.1-fold above baseline as compared with a 25.4 ± 4.2-fold increase in response to forskolin (10 µM). The PTH/PTHrP receptor antagonist PTHrP(7–34) significantly diminished the PTHrP(1–36)-induced cAMP increase. While superfusion of podocytes with bradykinin (100 nM) increased [Ca2+]i, PTHrP(1–36) (100 nM) was without effect on [Ca2+]i. However, PTHrP(1–36) attenuated the bradykinin-induced increase in [Ca2+]i. Our results suggest that PTHrP is an autocrine hormone in podocytes, which selectively activates the cAMP pathway through the PTH/PTHrP receptor.
Application of Bone Marrow-Derived Stem Cells in Experimental Nephrology
Authors: Ito Takahito , Suzuki Akira , Okabe Masaru , Imai Enyu , Hori Masatsugu
Published: April 2003

Recent advancement in developmental biology has led to the discovery of immature mesenchymal stem cells in bone marrow and several established organs. The therapeutic potentials of such stem cells for treating serious diseases constitute a major rationale for every research effort, and clinical trials for replacing some damaged tissues such as cartilage are currently under way. Although the feasibility of such stem cell therapies for renal diseases remains unknown, it is worthy of pursuing possibilities. As an experimental tool, we have made chimeric rats that carry the bone marrow of transgenic rats expressing green fluorescent protein (GFP) throughout the body. All marrow lineages can be traced with bright green fluorescence regardless of their terminal phenotypes in chimeric rats. When compared with other conventional strategies for tracking bone marrow-derived cells, our system is highly sensitive and allows us to take advantage of the rat nephrology. Using this system, we have reported that bone marrow provides mesangial cells during repair process. In this manuscript, we briefly summarize our experiences.
Comparisons of Speech Aerodynamics and Lateral Craniofacial Cephalometrics in Cleft Lip and Palate Patients with and without Finnish /r/-Sound Distortion
Authors: Laitinen Jaana , Hurmerinta Kirsti , Ranta Reijo , Sarmas Riitta , Haapanen Marja-Leena
Published: April 2003

To study the associations between the articulation of the Finnish /r/ sound and dentofacial and pharyngeal lateral cephalometric morphology and speech physiology, 18 (12 females, 6 males) young adult cleft patients’ /r/ sound was analysed auditorily by 3 speech experts. Laryngeal resistance (LARE), the smallest nasal cross-sectional area (NASA), nasal resistance (NASAR) and velopharyngeal orifice area (VEPA) were measured with pressure flow technique, and 31 points were identified from the lateral cephalograms to landmark the skeletal structure, pharyngeal airway diameters, and position of the hyoid bone. The present results showed no significant differences in lateral cephalometric skeletal, nasopharyngeal, oropharyngeal or hypopharyngeal morphology between subjects with and without /r/-sound distortion. There were no significant correlations either between /r/ distortions and NASA, NASAR or VEPA. An anteriorly positioned hyoid bone was significantly associated with decreased LARE and /r/ distortion. LARE was significantly lower in subjects with /r/ distortion.
Acquired Alexia in Multilingual Aphasia and Computer-Assisted Treatment in Both Languages: Issues of Generalisation and Transfer
Authors: Laganaro Marina , Overton Venet Mary
Published: April 2003

This single-subject study addresses the issue of investigation and remediation of an acquired reading impairment observed in a Spanish-English bilingual speaker. Detailed bilingual reading testing showed parallel disturbances in the two languages, both from a qualitative and a quantitative point of view, with characteristics of letter-by-letter and aphasic alexia. On the basis of this mixed pattern, common to both languages, a two-step computer-assisted remediation programme was designed for English, then for Spanish, using a crossover AB-AB design. Therapy A consisted of tasks aimed at the inhibition of letter-by-letter reading. This was alternated with therapy B, which was designed to address phonological assembly. Results on therapy reveal transfer of gains when common reading processing are involved and language-specific gains with a greater benefit on the mother tongue when phonological representations are required in therapy and assessment. Consequences for language choice in bilingual aphasia therapy are discussed on the basis of these results.
The Aging Voice: A Review, Treatment Data and Familial and Genetic Perspectives
Authors: Ramig Lorraine Olson , Gray Steven , Baker Kristin , Corbin-Lewis Kim , Buder Eugene , Luschei Erich , Coon Hillary , Smith Marshall
Published: April 2003

This paper will provide a review of aspects of vocal aging within the context of general body aging and describe two data sets related to the aging voice. Data will be presented which document pre- to posttreatment improvement in select voice characteristics (sound pressure level, subglottal air pressure, thyroarytenoid laryngeal muscle activity and voice quality) following application of an intensive voice treatment program (the LSVT®) to 3 individuals with aged voice. Additionally, physiological data (forced expiratory volume, visual accommodation, bone density, taste discrimination, white blood count and resting heart rate) and select perceptual (perceived age) and acoustic measures (reflecting both cycle-to-cycle and longer-term intensity and frequency stability) from 67 subjects will be reviewed from the work of Gray and colleagues to document the differential impact of the global aging process across organ systems including the aging voice.
Psychosocial Aspects of Aphasia: Whose Perspectives?
Authors: Parr Susie
Published: April 2003

This paper reviews some different meanings of the term ‘psychosocial’ and identifies the different ways in which the social and psychological sequelae of aphasia can be explored. These include qualitative methods, which seem well suited to addressing such complex issues. Having outlined some features of qualitative research, the paper describes a study in which fifty people talked about the consequences and significance of their long-term aphasia. Their ‘insider perspective’ on aphasia suggests its impacts are extensive, complex, direct and indirect, interconnected, systemic, dynamic and diversely experienced. The paper discusses the various implications of the study for clinicians and researchers concerned with the psychosocial aspects of aphasia and outlines how some of the issues raised in the interviews might be addressed.
Beziehung zwischen Messung der stimmlichen Durchdringungsfähigkeit, Stimmstatus nach Pahn und ausgewählten Parametern des Stimmanalyseprogramms MDVP (Kay)
Authors: Pahn Johannes , Dahl Rüdiger , Pahn Elke
Published: April 2003

Es wird ein Messverfahren der stimmlichen Durchdringungsfähigkeit im Störlärm vorgestellt. Der Lärm besteht aus einer Frequenzmischung von Vokalen mit stimmhaften und stimmlosen Konsonanten. Gemessen wird die Verständlichkeit der Testmatrix als Ausdruck der stimmlichen Durchdringungsfähigkeit von sprachverdeckendem Störlärm. Die Ergebnisse mit mehr als 1000 Patienten zeigen signifikante Korrelationen zur Einschwingphase des Stimmstatus und zu den subjektiven Angaben des Patienten betreffend das Lautstärkesteigerungsvermögen, die stimmliche Belastungsdauer und das stimmliche Wohlbefinden. Das Verfahren eignet sich damit zur Stimmdiagnostik, zur Therapieverlaufskontrolle, zur Begutachtung und zur Eignungsuntersuchung für stimm-sprachliche Professionen.
Comparison between the GIRBAS Scale and the Acoustic and Aerodynamic Measures Provided by EVA for the Assessment of Dysphonia following Unilateral Vocal Fold Paralysis
Authors: Morsomme Dominique , Jamart Jacques , Wéry Carine , Giovanni Antoine , Remacle Marc
Published: April 2003

The aim of this study is to establish relevant objective parameters for evaluating dysphonia following unilateral vocal fold paralysis. To do so, the study compares objective and perceptual voice measures. The objective measures were obtained using a voice analysis software (Evaluation Vocale Assistée), whereas the perceptual measures were established with the GIRBAS Scale (grade, instability, roughness, breathiness, asthenia, and strain). All measurements were performed on 40 voice samples: 28 dysphonic subjects with unilateral laryngeal paralysis, and 12 control subjects. The intra- and interjudge agreements were fairly good, at least for control subjects. The six GIRBAS measures obtained from the pathological voices were higher than those from the control voices (p < 0.001) and the correlation between both groups was good. Grade, breathiness and asthenia correlated with the objective parameters that express the aperiodicity of the phonatory signal (p < 0.01), namely, the coefficient of variability of the fundamental frequency, the coefficient of variability of intensity, and jitter. Our findings suggest that the perceptual reality of laryngeal paralysis-induced dysphonia depends more on grade, breathiness and asthenia than it does on roughness or instability.
Dysphonia Subsequent to Severe Traumatic Brain Injury: Comparative Perceptual, Acoustic and Electroglottographic Analyses
Authors: Jaeger M. , Fröhlich M. , Hertrich I. , Ackermann H. , Schönle P.W.
Published: April 2003

We tested the applicability of the Goettinger Hoarseness Diagram (GHD) for quantitative evaluation of voice disorders after severe traumatic brain injury (TBI) and compared the obtained data with those from established voice analysis systems such as the Multi-Dimensional Voice Program (MDVP), electroglottography (EGG) and perceptual ratings using sustained vowel productions from 10 patients with TBI dysarthrophonia at late stages postinjury and of 10 healthy control speakers. Statistical analyses revealed significant intergroup differences with respect to various acoustic and perceptual measures, i.e., irregularity component, noise component, noise-to-harmonic ratio, shimmer, jitter, roughness, creakiness, strained-strangledness, hypernasality. By contrast, the considered EGG estimates, i.e., open quotient and speed quotient, did not allow for separation of patients and controls. In addition, the two GHD components exhibited close correlations to perceived roughness and creakiness, on the one hand, and breathiness and, to some degree, nasality, on the other, whereas the MDVP parameters failed to differentiate between these two perceptual modes of phonation.
The Mechanics of Food Reduction in Tarsius bancanus
Authors: Crompton Robin Huw , Savage Russell , Spears Iain R.
Published: April 2003

The high-cusped, almost tritubercular teeth of Bornean tarsiers are used to reduce a wide variety of animal food. Prey is characteristically consumed entire, no parts being discarded. This paper attempts to identify the dental characteristics which permit tarsiers to reduce food substrates with widely varying mechanical properties and to assess whether reduction of some substrates incurs greater costs for tarsiers. Finite elements stress analysis (FESA) modelling is used to compare the effectiveness of tarsier and human teeth in reducing three types of food substrate habitually reduced by both species. Bone is taken as the exemplar of strong, stiff substrates, skin as the exemplar of substrates low in both stiffness and strength, and tendon as the exemplar of low-stiffness but strong substrates.The parameters used to measure performance are the work that must be done to bring tensile stresses to the point where tensile failure will be initiated and the bite-force required to do so. Human molars perform best in reducing bone, and tarsier molars in reducing skin. Neither perform as well in reducing tendon. Blunt, bunodont human molars perform slightly better than the high-cusped molars of tarsiers in reducing bone, but tarsier molars perform much better than human molars in inducing failure in skin and are also considerably better in reducing tendon. While the reduction effectiveness of human molars is greatly affected by substrate properties, the high cusps of tarsier teeth enable them to reduce foodstuffs of widely differing properties reasonably well. Scaling factors undoubtedly influence selection for cusp height, since high cusps are a prerequisite of effective crack propagation in food substrates by small animals. Microwear features do not show a consistent pattern where striations are associated with surface-parallel loads but pitting with surface-normal loads (at least as modelled by FESA). However, FESA modelling of the magnitude of applied forces and relative food/tooth displacement during occlusion suggest that the type of wear found in different regions is governed by the combined influences of relative tooth/food displacement and food/tooth reaction force. Pitting is associated with low levels of food/tooth displacement but high levels of reaction force, striation with high levels of displacement but low levels of force, and stripping or gouging of enamel with high values of both displacement and reaction force.
Acoustically Dimorphic Advertisement Calls Separate Morphologically and Genetically Homogenous Populations of the Grey Mouse Lemur (Microcebus murinus)
Authors: Hafen T. , Neveu H. , Rumpler Y. , Wilden I. , Zimmermann E.
Published: April 2003

Sexual advertisement calls of male mouse lemurs from two neighbouring demes in a dry deciduous forest of western Madagascar were recorded during the breeding season. Demes were located about 1.5 km apart with no geographic barrier between them. They were characterised morphometrically and genotyped by RAPD fingerprinting. According to univariate and multivariate statistical analysis, demes differed neither in body measurements, nor in the banding patterns produced by RAPD fingerprinting. The acoustic pattern of the advertisement call, however, showed significant differences: Six variables of the frequency and time domain differed between the demes. Discriminant function analysis revealed that one variable, total call duration, was sufficient to classify more than 89% of the calls correctly to the corresponding deme. We postulate that these differences are comparable to dialects in birds, because demes were morphologically and genetically indistinguishable and no barrier prevented genetic exchange between them. Possible explanations for the emergence of dialects in a prosimian species are outlined.
The Time of Divergence between the Two Species of Uacari Monkeys: Cacajao calvus and Cacajao melanocephalus
Authors: Boubli Jean Philippe , Ditchfield Albert David
Published: April 2003

It has been suggested in the literature that primates of the genus Cacajao have been restricted to flooded-forest habitats of western Amazonia since their split from the Chiropotes line in the Tertiary. It has been proposed further that the differentiation of the two species of this genus, Cacajao melanocephalus and Cacajao calvus, occurred during the Pleistocene period as a result of the fragmentation of the Amazon forest and the isolation of populations in these forest fragments or refuges. However, recent evidence has shown that at least C. melanocephalus is not dependent on flooded-forest habitats, and molecular analysis of mitochondrial DNA shows that the two species had already differentiated during the Pliocene, thus Pleistocene glaciations do not explain the speciation in Cacajao. Considering that C. melanocephalus and its closest relative, Chiropotes, inhabit terra firme forests, it is suggested that preference for flooded-forest habitats may be an apomorphy in C. calvus.
Strategies That Support Declining Cholinergic Neurotransmission in Alzheimer’s Disease Patients
Authors: Sirviö J.
Published: April 2003

With an increased public awareness of Alzheimer’s disease (AD), the last two decades have witnessed an immense research effort directed towards discovering the cause of AD with the ultimate hope of developing safe and effective pharmacological treatments. Biochemical and histopathological changes of neurotransmitter markers in the brains of AD patients both at postmortem and neurosurgical cerebral biopsy have demonstrated an association between a decline in learning and memory, and a deficit in cholinergic and associated excitatory amino acid neurotransmission. These observations illustrate the selective neurotransmitter pathology of AD. Accordingly, although there is presently no ‘cure’ for AD, a large number of potential therapeutic strategies have emerged that are designed to correct the loss of cholinergic neurotransmission in AD. Such strategies include increasing acetylcholine synthesis, enhancing its presynaptic synthesis and/or release, potentiating its pre- or postsynaptic action, obstructing its metabolism, or by influencing the function of cholinergic neurones themselves by administration of nerve growth factor or by trans-synaptic modulation. Indeed, the cholinesterase (ChE) inhibitors have gained the most attention. Adverse events limited the usage of the first ChE inhibitors, but more recently introduced, well-tolerated compounds, for example donepezil, have confirmed efficacy in delaying the deterioration of symptoms of AD, a valuable treatment target considering the progressive nature of the disease. Other agents which affect the cholinergic system, directly or indirectly, that are in the early stages of development for the treatment of AD are also discussed.
Life in a Retirement Village: Implications for Contact with Community and Village Friends
Authors: Buys Laurie R.
Published: April 2003

Background: Friends provide acceptance, companionship, emotional support, and are important to mental health. One reason that older adults give for seeking alternative accommodations is to reduce their loneliness and isolation. Objective: The purpose of this study was to investigate whether older adults living in a retirement village have varying amounts of contact with friends who live within the retirement village or in the wider community. Methods: Three hundred and twenty-three independently living residents of 25 retirement village sites were interviewed. Participants were asked a range of open and closed questions about the amount and kind of contact they had with co-resident friends and community-based friends. Results: Residents engaged in several weekly visits with village friends and maintained regular contact with community friends through telephone calls. Few residents engaged in community outings or participated in village activities with either village or community friends. Conclusion: The nature of living in close proximity with other people, influences the amount of informal contact they have with friends. For those older individuals who seek alternative accommodation due to isolation or loneliness, re-location to congregate-style accommodation may increase their social contacts and have a positive impact on their well-being.
Alleviating Constipation in the Elderly Improves Lower Urinary Tract Symptoms
Authors: Charach Gideon , Greenstein Alexander , Rabinovich Pavel , Groskopf Itamar , Weintraub Moshe
Published: April 2003

Background: Constipation and lower urinary tract symptoms (LUTS) very frequently occur in the elderly, and several reports have suggested that dysfunction in either one of these systems may affect the other. Most studies correlating rectal and bladder dysfunction, however, have been carried out in children or young women. Objective: To examine the effect of alleviating constipation on LUTS in the elderly. Methods: Fifty-two patients aged 65–89 (mean 72 ± 13) years with chronic constipation and LUTS participated in this prospective cohort study. Before treatment of constipation was initiated and on their monthly visits, patients completed a questionnaire regarding their constipation pattern, urinary symptoms, sexual function and mood, and underwent urinalysis. Urinary tract anatomy and residual urine were evaluated by abdominal ultrasound at the commencement and completion of the study. Patients were followed up for 4 months. Results: Treatment of constipation increased the number of weekly defecations from 1.5 ± 0.9 to 4.7 ± 1.2 (p < 0.001). Patients spent less time on the toilet (25 ± 2.1 versus 63 ± 1.9 min, p < 0.0001). Fewer patients reported urgency (16 versus 34, p < 0.001), frequency (25 versus 47, p < 0.001) and burning sensation during urination (6 versus 17, p < 0.05). There was improvement in the scoring of urgency, frequency and burning sensation (from a baseline of 52 to 126, 131 and 95, respectively, p < 0.001). Urinary stream disturbances improved in 32 of the 52 patients (p < 0.001). Residual urine volume decreased from 85 ± 39.5 to 30 ± 22.56 ml (p < 0.001). There was also a significant decrease in the number of patients with bacteriurial events (5 versus 17, p < 0.001), and an improvement in sexual activity and mood (p < 0.05). Conclusions: Our data demonstrated that medical relief of constipation significantly improves LUTS in the elderly which, in turn, improves the patient’s mood, sexual activity and quality of life.
Suspected Cardiac Syncope in Elderly Patients: Use of the 12-Lead Electrocardiogram to Select Patients for Holter Monitoring
Authors: Manchanda S. , Ehsanullah M.
Published: April 2003

Background: Results of 24-hour Holter monitoring in elderly patients are often unhelpful, since the prevalence of asymptomatic arrhythmias increases and their prognostic significance is unclear. We investigated the value of the resting electrocardiogram (ECG) in predicting significant findings on 24-hour Holter recordings in those suspected of having cardiac syncope. Objective: To see whether the resting 12-lead ECG can be used as a screening tool to select elderly patients suspected of having cardiac syncope for 24-hour ECG monitoring. Method: Comparison of resting 12-lead ECGs and 24-hour Holter tapes in 145 consecutive elderly outpatients suspected of having a cardiac cause for falls, dizziness, or syncope. Results: Four of 30 normal ECGs (13%) showed an abnormality on Holter monitoring as compared with 55 of the 115 abnormal ECGs (47.8%; chi = 11.7143, p < 0.005). In the ‘normal’ group the 4 abnormal Holter recordings all showed short runs of supraventricular tachycardia, and no intervention resulted. The 115 abnormal resting ECGs showed either ischaemia (n = 27), dysrhythmia (n = 28), sinus bradycardia (n = 22), or conduction defects (n = 38). The 55 of these which showed abnormalities on Holter recordings occurred mostly where the resting ECG showed dysrhythmia (n = 14/28; 50%), bradycardia (n = 19/22; 86.4%), and conduction defect (n = 17/38; 44.7%). Seven patients had complete heart block on Holter, and all had conduction defects on resting ECG (p < 0.0004). Fifteen patients had pauses of longer than 3 s on Holter; all had conduction defect, bradycardia, or dysrhythmias on resting ECG (p < 0.0045). Sixteen patients were paced because of complete heart block or pauses on Holter recordings, and all had either bradycardia or conduction defects on resting ECG, resulting in complete resolution of their symptoms. Conclusions: Patients with suspected cardiac syncope and normal resting ECGs are unlikely to reveal significant abnormalities on single 24-hour Holter monitoring. Cardiac event recorder or prolonged Holter monitoring may be required in patients with strong clinical history. Those with abnormal ECGs, in particular sinus bradycardia and conduction defects, are highly likely to have significant abnormalities on 24-hour ECG monitoring.
Natural Killer Activity and Thyroid Hormone Levels in Young and Elderly Persons
Authors: Kmieć Zbigniew , Myśliwska Jolanta , Rachoń Dominik , Kotlarz Grażyna , Sworczak Krzysztof , Myśliwski Andrzej
Published: April 2003

Background: On the basis that (1) multiple interactions exist between the hormonal and immune systems, and (2) aging is accompanied by changes in thyroid hormone metabolism and responsiveness, we postulate that thyroid hormones may be involved in the observed decrease in natural killer (NK) activity in a population of apparently healthy elderly subjects. The purpose of the study is to compare NK cytotoxic activity and serum concentrations of TSH and thyroid hormones in healthy old and young people, and to assess in vitro the effects of triiodothyronine (T3) on NK activity. Materials and Methods: Sixteen of the 47 healthy old people (mean age 64 ± 5.2) were classified as optimally healthy, and the remainder as ‘almost healthy’ (according to the criteria of the Senieur protocol) [Ligthart et al., Mech Ageing Dev 1984;28:47–55]; the mean age of the healthy young people was 23.3 ± 2.3 years. NK cytotoxic activity of peripheral blood mononuclear cells was assessed using 51Cr release from K562 target cells. The cutoff level for defining low and high NK responses was set at a value of 20%. Serum concentrations of TSH, total thyroxine (T4) and total triiodothyronine (T3) were measured by radioimmunoassay. Results: NK activity in the ‘optimally healthy’ elderly was high (mean 41 ± 12%, SE), whereas ‘almost healthy’ subjects showed low NK activity (mean 6 ± 5%). Serum T4 and TSH levels, but not T3 concentrations were similar in both the young and old. We observed a significant correlation (r = 0.53, n = 21, p < 0.05) between the serum total T3 level and the NK activity in the elderly individuals. Under in vitro conditions exogenous T3 significantly increased NK activity in the elderly subjects who had serum T3 values at the lower end of the reference range. However, no effect of T3 on NK activity was observed in peripheral blood mononuclear cells obtained from either old or young individuals who had serum T3 levels at the midpoint of the range. Conclusion: Decreased serum concentrations of total T3 may contribute to low NK activity in the ‘almost healthy’ subgroup of the elderly.
Benefit of GnRH Analogue Pretreatment for Hysteroscopic Surgery in Patients with Bleeding Disorders
Authors: Römer Thomas
Published: April 2003

Hysteroscopic surgery is widely used for the treatment of patients suffering from menorrhagia. In different studies, pretreatment of the endometrium with GnRH analogues (GnRH-a) prior to endometrial ablation has been reported to increase the success rate, as well as to reduce the menstrual blood flow, accounting for a significantly higher postoperative amenorrhea rate (42% in pretreated patients vs. 24% in those receiving no pretreatment). The aim of pretreatment is not only to obtain a thin endometrium but also to reduce the size and vascularization of myomas being treated. In our study, GnRH-a administration prior to endometrial ablation was shown to have the following advantages: improved hysteroscopic view, reduced blood loss, absorption of uterine distending fluid and higher postoperative amenorrhea rates. Prior to hysteroscopic myoma resection, pretreatment with GnRH-a may be particularly indicated for all myomas with a diameter of more than 3 cm and/or with an intramural portion, or for patients suffering from secondary anemia. GnRH-a pretreatment is thus indicated before endometrial ablation, and in most cases, before hysteroscopic resection of submucous myomas, and combined medical and surgical therapy has clear benefits in the treatment of bleeding disorders.
Role of Cytokines in Progression of Endometriosis
Authors: Harada Tasuku , Enatsu Akiko , Mitsunari Masahiro , Nagano Yorie , Ito Masayuki , Tsudo Toshiyuki , Taniguchi Fuminori , Iwabe Tomio , Tanikawa Masahiro , Terakawa Naoki
Published: April 2003

Peritoneal fluid in women with endometriosis contains an increased number of activated macrophages that secrete a variety of cytokines, including interleukin (IL)-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor-α (TNF-α). Cytokines may be involved in the control of implantation and the growth of endometrial cells outside the uterus. In addition, several cytokines have been implicated in or directly associated with angiogenic activity in endometriosis. There could be a relationship between the levels of cytokines in the peritoneal fluid of patients with endometriosis and the status of the lesions in such patients. Peritoneal endometriosis can be classified as having red, black, or white lesions. Red lesions are known to be an active form of early endometriosis, because vascularization and mitotic activity are shown to be most prominent in these lesions. We found that the peritoneal fluid levels of TNF-α and IL-8 were significantly higher in patients with endometriosis, and correlated with the size and number of active lesions. In addition, TNF-α and IL-8 stimulated the growth of ectopic endometrial stromal cells. These cytokines with angiogenic activity may therefore have significant roles in the pathogenesis of endometriosis.
Molecular Genetic Defects in Endometriosis
Authors: Thomas Eric J. , Campbell I.G.
Published: April 2003

In a series of studies, we have hypothesised that endometriotic proliferation is, in part, precipitated by mutations in oncogenes or deletions in tumor suppressor genes that have been shown to be important steps in the transformation from a benign to a malignant epithelium. We reported previously that we could find no mutations in the TP53 and RASK genes in cases of endometriosis. However, having shown that endometriotic deposits were monoclonal, we showed loss of heterozygosity on chromosomes 9p (18%), 11q (18%), and 22q (15%) – in total 28% of endometriotic lesions showed loss of heterozygosity at one or more sites [1]. We could not demonstrate any loss of heterozygosity in normal endometrium. We examined adjacent endometriosis, atypical endometriosis, and endometrioid carcinoma of the ovary and showed common genetic alterations that are consistent with a common lineage. These common alterations were not seen in lesions that were distant from each other [2]. In endometrioid tumors, we reported an increased frequency of mutations in the PTEN/MMAC tumor suppressor genes that was not seen in clear cell or serous carcinoma, suggesting distinct developmental pathways for these tumors [3].