bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult Neurogenesis and Neuronal Regeneration in the Central Nervous System of Teleost Fish
Authors: Zupanc Günther K.H.
Published: April 2003

In contrast to mammals, teleost fish exhibit an enormous potential to produce new neurons in the adult central nervous system and to replace damaged neurons by newly generated ones. In the gymnotiform fish Apteronotus leptorhynchus, on average, 100,000 cells, corresponding to roughly 0.2% of the total population of cells in the adult brain, are in S-phase within any 2-h period. As in all other teleosts examined thus far, many of these cells are produced in specific proliferation zones located at or near the surface of ventricular, paraventricular, and cisternal systems, or in areas that are likely derived from proliferation zones located at ventricular surfaces during embryonic development. The majority of cells born in such proliferation zones migrate within the first few weeks following their generation to specific target areas. In the cerebellum, where approximately 75% of all brain cells are born during adulthood, cells originate from the molecular layers of the corpus cerebelli and the valvula cerebelli partes lateralis and medialis, as well as from the eminentia granularis pars medialis. From these proliferation zones, the young cells migrate to the associated granule cell layers or to the eminentia granularis pars posterior, respectively. In the course of their migration, the young cells appear to be guided by radial glial fibers. Upon arrival at their target region, approximately 50% of the young cerebellar cells undergo apoptosis. The remaining cells survive for the rest of the fish’s life, thus contributing to permanent brain growth. At least some cells differentiate into granule cell neurons. The potential to produce new neurons, together with the ability to guide the young cells to their target areas by radial glial fibers and to eliminate damaged cells through apoptosis, also forms the basis for the enormous regenerative capability of the central nervous system of Apteronotus, as demonstrated in the cerebellum and spinal cord. A factor involved in the cerebellar regeneration appears to be somatostatin, as the expression of this neuropeptide is up-regulated in a specific spatio-temporal fashion following mechanical lesions. Besides its involvement in neuronal regeneration adult neurogenesis in Apteronotus, and possibly teleost fish in general, appears to play a role in providing central neurons to match the growing number of sensory and motor elements in the periphery, and to establish the neural substrate to accommodate behavioral plasticity.
Stem Cells in the Vertebrate Retina
Authors: Reh Thomas A. , Fischer Andrew J.
Published: April 2003

The capacity for retinal regeneration in cold-blooded vertebrates has long been recognized. Regeneration occurs, in part, through a population of retinal stem cells residing at the peripheral margin of the retina. It has generally been thought that homeothermic vertebrates, such as birds and mammals, lack this so-called ciliary marginal zone. Recent studies have, however, provided evidence that birds too possess a zone of cells at the retinal margin analogous to the ciliary marginal zone of fish and amphibians. In addition, there is an indication that, under certain conditions, Müller glia of the chicken retina can transdifferentiate into retinal progenitor/stem cells. These progenitor/stem cells then generate certain types of retinal neurons. Taken together, these studies have revealed an unexpected capacity for retinal regeneration in birds.
Validity and Reproducibility of a Laser Fluorescence System for Detecting the Activity of White-Spot Lesions on Free Smooth Surfaces in vivo
Authors: Pinelli Camila , Campos Serra Mônica , de Castro Monteiro Loffredo Leonor
Published: April 2003

The aim of the study was to determine the reproducibility and validity of DIAGNOdent in detecting active and arrested caries lesions on free smooth surfaces. Volunteers were selected from state schools of Piracicaba, São Paulo, Brazil. Overall, 220 lesions were clinically examined. Two specially trained (‘calibrated’) examiners performed both clinical and laser evaluations independently, and after a 1-week interval, the examinations were repeated. The intra-examiner agreement for the laser evaluation was substantial (ĸex1 = 0.79, ĸex2 = 0.71). There was almost perfect agreement between the two examiners for the clinical examination (ĸex1 = 0.95, ĸex2 = 0.85). The inter-examiner agreement showed substantial reproducibility (ĸ = 0.77) for the laser examination and almost perfect agreement (ĸ = 0.85) for the clinical evaluation. The validation criterion was the clinical examination of white spots, recorded as active or arrested. The sensitivity was 0.72 and the specificity was 0.73, which indicates that the DIAGNOdent was a good auxiliary method for detecting incipient caries lesions on free smooth surfaces. The utilization of both methods can improve the efficacy of caries diagnosis.
The Influence of Salivary Variables on Fluoride Retention in Dental Plaque Exposed to a Mineral-Enriching Solution
Authors: Kato K. , Nakagaki H. , Arai K. , Pearce E.I.F.
Published: April 2003

This study was carried out to examine interindividual differences in salivary variables related to plaque accumulation and to estimate their influence on the fluoride retention in plaque in vivo by a mineral-enriching solution. Two saliva samples were taken from 10 subjects, once after brushing and once after 24 h without brushing. Calcium, phosphate and monofluorophosphatase (MFPase) activity in the saliva samples were determined. The salivary flow rate and the debris index were also recorded. After plaque had formed over 3 days within in situ plaque-generating devices, subjects were instructed to rinse with a mineral-enriching mouthrinse three times a day on 4 consecutive days. Plaque exposed to distilled water plus flavoring agents served as a control. Fluoride-free dentifrice was used during the experimental period. Twenty-four hours after the last rinsing, the samples were removed from the mouth, and fluoride and mineral distributions in plaque analyzed using a method previously reported by the authors. Salivary flow, MFPase activity and calcium concentration in saliva were significantly higher after 24 h of plaque accumulation. Rinsing with the mineral-enriching solution produced retention of fluoride and phosphate in the outer and middle layers of plaque. Salivary calcium concentration had a direct effect on fluoride uptake in plaque, but no obvious relationship was found between other salivary variables and the plaque fluoride retention. The salivary calcium effect may be due to enhanced bacterial cell wall binding of fluoride via calcium bridging.
Fluoride and Urea Chewing Gums in an Intra-Oral Experimental Caries Model
Authors: Sjögren K. , Ruben J. , Lingström P. , Lundberg A.-B. , Birkhed D.
Published: April 2003

The aim of the present investigation was to evaluate the effect of sugar-free chewing gums containing fluoride (F) and urea in an intra-oral experimental caries model. Placebo chewing gums (without any active ingredient) and no gum served as controls. Fifteen subjects participated in a cross-over, single-blind study. Demineralised enamel and dentine blocks were embedded in circular plastic discs and bonded to the buccal surfaces of the lower canines and first premolars. The discs were removed and analysed using transversal microradiography after each of the six 4-week periods during which the subjects used either test or placebo products or no product. The results revealed that frequent use of sugar-free chewing gum is sufficient to inhibit further demineralisation of previously demineralised enamel and dentine specimens in the oral cavity. Comparing F, urea and placebo gums, the data showed that there was little or no difference between the products, except for an inhibitory effect on the chewing side of the dentition after using F chewing gums.
Comparison of the Humoral Markers of Bone Turnover and Bone Mineral Density in Patients on Haemodialysis and Continuous Ambulatory Peritoneal Dialysis
Authors: Hampson G. , Vaja S. , Evans C. , Chesters C.A. , Pettit R. , Evans W. , Thomas D. , Seed P.T. , Fraser W.D.
Published: April 2003

Renal osteodystrophy is an important complication in patients with end-stage renal disease on maintenance dialysis. The aim of this study was to compare the biochemical markers of bone formation (serum collagen type I C-terminal propeptide) and resorption (serum deoxypyridinoline – DPD – and pyridinoline – PYR) with the bone mineral density (BMD) at lumbar spine, femoral neck, and forearm in patients with end-stage renal disease on haemodialysis (HD) versus continuous ambulatory peritoneal dialysis (CAPD). Fifty-nine adult patients, 45 on CAPD (18 females, 27 males) and 14 on HD (2 females, 12 males), were studied. The mean age was 44 ± SEM 1.6 and 54.4 ± 4.8 years, respectively. No significant differences in serum calcium, phosphorus, creatinine, and parathyroid hormone were found between patients on HD and CAPD in predialysis samples. Serum urea was significantly lower (p = 0.02) in the CAPD group. Serum PYR (nmol/l) and DPD (nmol/l) were significantly higher in patients on HD as compared with those on CAPD: 105 ± 23.3 versus 43.7 ± 3.47 (p = 0.007) and 31.0 ± 2.4 versus 24.4 ± 1.4 (p = 0.027), respectively. The results were still significantly higher in the HD patients following correction for serum creatinine and body mass index. There was a close correlation between dialysate DPD and creatinine in both dialysis modalities (HD r = 0.9, CAPD r = 0.76). The clearance of DPD did not differ significantly between the CAPD membrane and the HD membrane (p = 0.22). Serum collagen type I C-terminal propeptide was not significantly different between the HD and CAPD patients. The results were unaffected following correction for age and gender. The BMD was measured in 38 (65%) of the patients (HD n = 8, CAPD n = 30) by dual-energy X-ray absorptiometry and expressed as ‘Z’ scores. This was reduced at all sites in the patients with end-stage renal disease. The BMD was significantly lower at the ultradistal forearm (mostly trabecular bone) in HD patients as compared with CAPD patients (n = 0.02). A similar trend was observed at the lumbar spine, although the results failed to reach significance. In the whole population (n = 38), linear regression analysis revealed a significant negative correlation between BMD at the ultradistal forearm and serum PYR (r = –0.35, p = 0.04) and DPD (r = –0.33, p = 0.049). Combined measurements of BMD and biochemical markers of bone resorption may have potential in the identification of patients at high risk of bone loss who may require further evaluation of bone remodeling by bone histomorphometry.
Using Tandem Scanning Confocal Microscopy to Predict the Status of Donor Kidneys
Authors: Andrews Peter M. , Khirabadi Bijan S. , Bengs Benjamin C.
Published: April 2003

Tandem scanning confocal microscopy (TSCM) is a noninvasive form of vital microscopy that can be used to evaluate superficial uriniferous tubules in living kidneys. Because TSCM has a number of advantages over conventional microscopic examination of renal biopsies, the present study was undertaken to determine whether the histopathological images obtained by TSCM correlate with post-transplant renal function. The kidneys of New Zealand male rabbits were harvested, flushed with Euro-Collins solution, and stored at 0–2°C for periods of 24, 48, 67 and 72 h prior to transplantation. TSCM observation of the kidneys prior to their transplantation revealed characteristic histopathological changes of the superficial proximal convoluted tubules that correlated closely with subsequent post-transplant renal function. These observations indicate that TSCM may be of significant value in evaluating the status of donor kidneys prior to their transplantation.
Brucella Peritonitis in a Patient on Continuous Ambulatory Peritoneal Dialysis with Acute Brucellosis
Authors: Taskapan Hulya , Oymak Oktay , Sümerkan Bülent , Tokgoz Bülent , Utas Cengiz
Published: April 2003

Peritonitis is an uncommon complication of brucellosis. Brucella peritonitis in chronic ambulatory peritoneal dialysis (CAPD) patients has not been reported before. A male patient is presented with peritonitis caused by Brucella melitensis who was on CAPD. The source of infection was thought to be unpasteurized, unsalted cheese eaten a month before the onset of symptoms. At the beginning, antibiotic therapy with doxycyline and rifampicin led to a rapid clinical improvement, with disappearance of the organism in the peritoneal fluid. However, peritonitis relapsed after discontinuation of antimicrobial therapy. Successful management required a combination of medical therapy and removal of the Tenckhoff catheter.
Membranous Glomerulonephritis in a Patient with Unilateral Renal Agenesis
Authors: Watanabe Toru
Published: April 2003

Secondary membranous glomerulonephritis (MGN) is usually caused by drugs or systemic disorders that produce circulating immune complexes. However, some disorders that did not seem to form circulating immune complexes have been listed as underlying diseases of secondary MGN. The case of a 13-year-old boy with MGN and unilateral renal agenesis is presented. Renal histology showed segmental MGN with mesangial proliferation and mesangial electron-dense deposits, and no other underlying disorder except for unilateral renal agenesis. Patients with MGN, who have histological findings suggesting secondary MGN and no underlying disorder distinctly causing formation of circulating immune complexes, should not be defined as having idiopathic or secondary forms, but as having a ‘cryptogenic’ form.
Studies of 13C-Urea Breath Test for Diagnosis of Helicobacter pylori Infection in Patients after Partial Gastrectomy
Authors: Kubota Keisuke , Shimoyama Shouji , Shimizu Nobuyuki , Noguchi Chiaki , Mafune Ken-ichi , Kaminishi Michio , Tange Tsuyoshi
Published: April 2003

Background/Aims: Many of the reports on the diagnostic efficacy of the 13C-urea breath test (13C-UBT) for the detection of Helicobacter pylori in the residual stomach have shown negative results. We conducted an evaluation to establish a standardized protocol and an appropriate cutoff value for 13C-UBT in partial gastrectomy patients. Methods: Forty-two patients undergoing partial gastrectomy were included. Three gastric biopsies from the anastomotic site and mid-to-high body were taken at panendoscopy for histology, culture and rapid urease test (RUT). The 13C-UBT protocol included ingestion of 100 mg 13C-urea, use of mouthwash, and the body in a horizontal position on the left side. Six breath samples were taken after ingestion. Results: The Δ13CO2 values were significantly elevated in infected patients at all time points, and values were higher at 20 min and thereafter than at an earlier time point. The sensitivity of 13C-UBT was 96.3% with the cutoff of 2.0‰ at 40 min. The accuracy rates were highest with 13C-UBT, culture, RUT and histological tests, in that order. Conclusion: Forty minutes and a cutoff of 2.0‰ were found to be optimal for the test, with the body position horizontal on the left side. In the present protocol 13C-UBT appears to be a reliable tool with the same accuracy rate as other routine tests in patients with a remnant stomach.
Interferon-Alpha in Combination with Ribavirin for the Treatment of Chronic Hepatitis C in Patients with Persistently Normal Aminotransferase Levels
Authors: Hasan Fuad , Asker Haifa , Al-Khalid Jameela , Al-Mekhaizeem Khalid , Al Shamali Mohammed , Siddique Iqbal , Al Nakib Basil
Published: April 2003

Background and Aims: A substantial proportion of patients with chronic hepatitis C virus infection have persistently normal serum transaminase levels. The aim of this study was to assess the efficacy and safety of interferon plus ribavirin combination therapy in this population. Methods: In this prospective open trial 152 patients with biopsy-proven chronic hepatitis C were enrolled, 32 of whom had persistently normal alanine aminotransferase levels (group A). The remaining 120 patients served as a comparison (group B). Patients were treated for 12 months with 4.5 million units of interferon-α2a thrice weekly in combination with ribavirin 1,000 or 1,200 mg daily. They were followed up for at least 6 months after therapy. Serum hepatitis C RNA was detected by polymerase chain reaction and quantified by a branched DNA assay. Results: At the end of treatment, 12 (37.5%) and 48 patients (40%) were negative for HCV-RNA in groups A and B, respectively (p = 0.33). After 24 weeks of follow-up, 9 patients (28%) from group A and 36 patients (30%) from group B were still HCV-RNA negative (p = 0.4). Treatment was well tolerated by both groups. There were no alanine transferase elevations among group A patients during therapy. Conclusion: Interferon-ribavirin combination therapy was safe and induced a sustained virologic response in a significant proportion of patients with chronic hepatitis C and repeatedly normal serum transaminase levels.
Antimicrobial Effectiveness of Povidone-Iodine and Consequences for New Application Areas
Authors: Reimer K. , Wichelhaus T.A. , Schäfer V. , Rudolph P. , Kramer A. , Wutzler P. , Ganzer D. , Fleischer W.
Published: April 2003

The microbicidal action spectrum of povidone-iodine (PVP-I) is broad – even after short onset times. Unlike local antibiotics and other antiseptic substances, no resistance develops. The high degree of bactericidal efficiency in respect of highly resistant gram-positive pathogenic micro-organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) and enterococcus strains, is particularly significant for hospital hygiene. An in vitro study with 10 genotypically different MRSA isolates showed an optimum bactericidal effect (logarithmic reduction factor value >5) without protein load after just 30 s exposure and even in a dilution of Betaisodona® solution (Mundipharma GmbH) of 1%. With protein load (0.2% albumin), the optimum in microbicidal effectiveness shifts to concentrations ≧10% Betaisodona solution referring to an exposure time of 30 s. Since recent results are now also available on the toxicological safety of PVP-I preparations for the ciliated epithelium of the nasal mucosa and the good tolerability on skin and other mucous membranes is a known factor, a controlled clinical study is currently being carried out to eliminate colonizations of MRSA. Evidence has also recently been produced of the antiviral activity of PVP-I against herpes simplex, adeno- and enteroviruses, as well as its high degree of efficiency against Chlamydia. Hence alongside the classical fields of application, such as the disinfection of the skin and hands, mucosa antisepsis and wound treatment, there are also useful indications for the substance, i.e. rinsing of body cavities and joints and application to the eye.
Measurement of Inflammatory Mediators of Eosinophils and Lymphocytes in Blood in Acute Asthma: Serum Levels of ECP Influence the Bronchodilator Response
Authors: Di Lorenzo Gabriele , Pacor Maria Luisa , Morici Giuseppina , Drago Agata , Esposito-Pellitteri Maria , Candore Giuseppina , Lo Bianco Claudia , Caruso Calogero
Published: April 2003

The aim of this study was to assess the relevance of immunoinflammatory markers on the response to short acting β2-agonist in acute asthma exacerbation. Thus, we measured serum eosinophil cationic protein (ECP) levels and sIL-2R at acute exacerbation in 52 adult patients with atopic asthma, and assessed forced expiratory volume in 1 s (FEV1) before and after the administration of aerosolized salbutamol. After a cumulative dose of salbutamol causing a 10% improvement in FEV1 from baseline [CD10, i.e. cumulative doses of salbutamol (800 µg) causing an improvement in FEV1 from baseline to 10%] the patients were divided into two groups: group A with CD <10 and group B with CD >10. The bronchodilator response, as defined by a ΔFEV1 (percentage of predictive value of FEV1) of ≧10 predictive value, was shown by 40% of the patients. After 200, 400 and 800 µg of salbutamol, significant differences of FEV1 with respect to baseline values were, respectively, p = 0.049, 0.0039 and 0.0014. In contrast, no significant difference of the means of FEV1 between the doses of salbutamol was observed. Significant differences of ΔFEV1 between 200 and 400 µg (p = 0.0002) and between 200 and 800 µg (p < 0.0001) were observed, but not between 400 and 800 µg of salbutamol. There were significant correlations between baseline values of predictive FEV1 and serum ECP levels (rho = –0.60, p < 0.0001) and sIL-2R levels (rho = –0.35, p = 0.01) respectively. Besides, a correlation between ΔFEV1 and serum ECP levels (rho = –0.53, p < 0.0001) was observed, whereas no correlation was found between ΔFEV1 and sIL-2R. By analyzing differences between the two groups (A and B) for serum ECP levels, sIL-2R and blood eosinophil count, a significant difference was found for serum ECP levels. We conclude that subjects with acute exacerbation of asthma show high serum levels of ECP and sIL-2R and, more interestingly, that the response to brochodilator was higher in patients with lower serum ECP levels.
Tuning of T Cell Clone Size and Activation Threshold by Control of CD25 Expression through Mitogen-Activated Protein Kinase Pathways
Authors: Bitegye Christina , Hannier Sigrid , Guérif Stéphane , Valitutti Salvatore , Demotz Stéphane
Published: April 2003

Background: Following T cell receptor (TcR) engagement, CD25 expression is upregulated by T cells and controls their proliferation. It is not known how CD25 expression levels differentially influence T helper (Th) 1 and Th2 cell physiology. Method: CD25 upregulation, and other T cell functions, were studied in human Th1 and Th2 clones following stimulation with various stimuli. The effects of pharmacological substances were then evaluated to identify the signaling pathways controlling CD25 upregulation. Results: Upon TcR engagement, one Th2 clone was induced to express substantially more CD25 than a Th1 clone, although both clones downregulated CD3 with similar dose responses. It was also found that the amount of antigen needed to elicit proliferation and cytokine production was considerably lowered in the presence of interleukin-2 (IL-2) for the Th2 cells, while for the Th1 cells the threshold of activation was not modified by the presence of IL-2. It was then shown that PP2 and cyclosporin A strongly inhibited CD25 expression in both clones, while wortmannin and Ro-31-8220 had more limited effects. In contrast, mitogen-activated protein kinase (MAPK) inhibitors had strikingly different effects on CD25, blocking its expression in the Th2 cells, while augmenting it, or leaving it unaffected, in the Th1 cells. Conclusion: These unexpected observations suggested that in some T cells TcR-mediated activation of the MAPK pathways may inhibit CD25 expression rather than promoting it. Absence of this negative control mechanism may endow Th2 cells with a growth advantage over Th1 cells and their effector functions may be elicited at lower antigen doses.
mRNA Expression of Multiple Cytochrome P450 Isozymes in Four Types of Cultured Skin Cells
Authors: Saeki Mayumi , Saito Yoshiro , Nagano Michiyo , Teshima Reiko , Ozawa Shogo , Sawada Jun-ichi
Published: April 2003

Background: Many drugs are known to induce allergic reactions in the skin. The metabolic activation of drugs resulting in the formation of protein adducts is thought to be a first step in the induction of these allergic reactions. We postulated that dermal tissue might be a site of drug activation by cytochrome P450 (CYP) isozymes. Methods: Messenger RNA was extracted from cultured Langerhans cells, keratinocytes, fibroblasts and melanocytes from 6 individuals, and CYP mRNA expression was analyzed by RT-PCR. Results: CYP1A1, 1B1 and 2E1 were found in all four cell types. CYP2A6, 2C, 2D6, 3A5, 3A7 and 4B1 mRNA was expressed in a cell-type- and/or individual-specific manner. CYP1A2, 2A7, 2B6 and 3A4 mRNA was not detectable. Conclusions: The mRNA for a variety of CYP isozymes was expressed in all four types of skin cells examined. These CYP enzymes may be involved in the pathogenesis of drug-induced allergic reactions in the skin.
Vaccination and Otitis media
Authors: Karma P.
Published: April 2003

Acute otitis media (AOM) caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis may induce specific systemic and/or local immune responses, which may protect from otitis media caused by the same bacteria. However, earlier clinical trials with pneumococcal capsular polysaccharide vaccines have not been successful in preventing AOM. Recently developed pneumococcal polysaccharide-protein conjugates proved immunogenic even in infants, and a heptavalent pneumococcal CRM 197 conjugate vaccine gave a 57% reduction in the number of pneumococcal AOM episodes caused by the vaccine serotypes in infants in Finland. H. influenzae causing AOM is noncapsulated, and like M. catarrhalis, calls for another kind of vaccine development. Suitable vaccine candidates are not yet available but are under development and being tested for immunogenicity and safety. In some trials influenza vaccines have shown protection from AOM during respective viral epidemics. Passive immunoprophylaxis might be an important alternative for immunocompromised children, although this approach has not been successful so far. Mucosal immunization and the advent of DNA and gene technology will open new interesting prospects in the future.
Endolymphatic Deafness: A Particular Variety of Cochlear Disorder
Authors: Tran Ba Huy Patrice
Published: April 2003

Experimental and clinical data made us consider some types of perceptive hearing loss secondary to an alteration of the secretory structures of the cochlea including stria vascularis, spiral ligament and supporting cells. These structures are responsible for the secretion of endolymph, a fluid characterized by a high potassium concentration (150–180 mM), a low sodium concentration (<1 mM) and a positive potential (80–100 mV). This intracellular-like fluid fills the endolymphatic compartment and is essential in the transduction process which takes place in the organ of Corti. Experimental studies have shown that drugs such as loop diuretics induced marked histological lesions in the stria vascularis and profound alterations in the electrochemical features of endolymph. Histopathological data have demonstrated that several entities such as prebyacusis, sudden deafness, and congenital or acquired progressive hearing loss could be related to strial abnormalities. Recent genetic studies have shown that a mutation of genes encoding connexins, a gap junction protein present in the secretory structures, was involved in some dominant or recessive forms of congenital deafness. Finally, the evaluation of labyrinthine fluids in humans has evidenced a decreased endocochlear potential in two cases of progressive flat hearing loss. All these arguments suggest that among the various types of so-called ‘sensorineural’ deafness, several entities including strial presbyacusis, diuretic-induced ototoxic deafness, some forms of congenital hearing loss and sudden deafness should be classified as endolymphatic deafness. Such an identification seems necessary since these entities result from different pathogenetic mechanisms, do not have the same evolution nor will they probably benefit from the same therapeutic management.
The Endolymphatic Sac: A Scanning and Transmission Electron Microscopy Study
Authors: Qvortrup Klaus , Bretlau Poul
Published: April 2003

A recent investigation has suggested that the chief cells of the endolymphatic sac produce an endogenous inhibitor of sodium resorption in the kidneys, tentatively named saccin. In the current study, the ultrastructure of the endolymphatic sac and in particular the chief cells are described to demonstrate that this organ fulfils the morphological criteria of a potential endocrine gland. Accordingly, the chief cells are shown to exhibit all the organelles and characteristics of cells that simultaneously synthesize, secrete, absorb and digest proteins.
Collagenous Spherulosis in Epithelial-Myoepithelial Carcinoma of the Parotid Gland
Authors: Böőr A. , Jurkovič I. , Kočan P. , Jenča A.
Published: April 2003

Previously unreported histological and immunohistochemical features of collagenous spherulosis in an epithelial-myoepithelial carcinoma found in an 80-year-old woman are described. The multinodular tumor located in the right parotid gland was completely removed surgically. No local recurrence of the tumor appeared during the 22-month period of periodic checkups. This is believed to be the first report on collagenous spherulosis in an epithelial-myoepithelial carcinoma of the salivary gland. Different immunohistochemical characteristics of epithelial and myoepithelial neoplastic cells were found very useful for their analysis namely in parts of the tumor where one cell type greatly predominated (e.g. clear cell-type predominance). The double staining of histological sections can in this sense be recommended for the differentiation from other clear cell tumors of salivary glands allowing the correct categorization of the neoplasm.
Tortuosity of the White Matter Medullary Arterioles Is Related to the Severity of Hypertension
Authors: Hiroki Masahiko , Miyashita Kotaro , Oda Masaya
Published: April 2003

Background: The clinical implication of the tortuosity of white matter medullary arterioles has never been clarified precisely. We quantitatively investigated the relationship between such vascular tortuosity and the severity of hypertension (HT), which was graded according to the WHO classification. Methods: Forty-seven autopsied brains with age-adjusted stages of HT were evaluated. The largest tortuosity diameter and the largest vascular diameter in the same tortuous lesion were measured by light microscopic observation at the level of the corona radiata and centrum semiovale. A maximum ratio of these diameters was calculated for each patient. Results: Maximum ratios were found in almost all arterioles and were significantly increased according to the HT stages. Conclusions: Arteriolar tortuosity in the hemispheric white matter may reflect the severity of HT and be an indicator of hypertensive small vessel disease of the brain.
The Effect of Sucrose Application Frequency and Basal Nutrient Conditions on the Calcium and Phosphate Content of Experimental Dental Plaque
Authors: Pearce E.I.F. , Sissons C.H. , Coleman M. , Wang X. , Anderson S.A. , Wong L.
Published: April 2003

A reduced pool of calcium in dental plaque would be expected to increase the ability of plaque fluid to dissolve the underlying enamel when the pH falls during sugar exposure. We have examined the relationship between frequency of sugar application and Ca and Pi concentrations in artificial mouth plaque microcosm biofilms. Ten plaques were grown simultaneously from a human saliva inoculum using a continuous flow of simulated saliva, DMM, supplemented with either urea or glucose to modulate the resting pH. In addition the plaques received sucrose applications of varying frequency: 12-, 8-, 6-, or 4-hourly, or not at all. After 15 days the plaques were sampled by taking 4 full-thickness specimens of each, and acid-extractable Ca and Pi, and alkali-soluble protein and carbohydrate were determined. Ca and Pi concentrations were in a range comparable with those in human plaque, except in the DMM + urea plaque receiving no sucrose, when concentrations were higher. Plaque Ca concentration decreased significantly as sucrose application frequency increased. Increasing sucrose application frequency also reduced the protein, i.e. the cell biomass, content of the plaques and, in the case of DMM + urea plaques, increased the water-insoluble hexose content, presumably extracellular polysaccharide. Reduced biomass was partly due to the bulking of plaque with extracellular polysaccharide, but the marked effect of urea on polysaccharide formation is not understood. This study shows that increasing frequency of sugar application alters dental plaque by reducing its mineral protection capacity.
Influence of Antibody on the Structure of Glucans
Authors: Kopec Leslie K. , Vacca Smith Anne M. , Wunder David , Ng-Evans Linda , Bowen William H.
Published: April 2003

Glucosyltransferase (GTF) plays an essential role in the formation of the biofilm known as dental plaque and in the pathogenesis of dental caries. Mutans streptococci produce at least three distinct GTFs (GtfB, C and D), each of which forms a glucan polymer from sucrose. Glucan is a major constituent of plaque biofilm. GTF adsorbed to a surface forms glucans that differ in structure from those formed by the same enzyme in solution. In the present study, activities of GtfB and GtfC in solution or adsorbed on a surface were inhibited in the presence of a polyclonal antiserum (DS-1) to a mixture of GTFs and by immunoglobulin G (IgG) prepared from DS-1; in contrast, enzyme activity was enhanced by normal rabbit serum (NRS) and IgG from NRS. GtfD activity on a surface was enhanced by both antiserum DS-1 and NRS, and IgG prepared from either serum; GtfD activity in solution was slightly inhibited by each of the sera. The structure of GtfB and GtfC glucans formed in the presence of antiserum differed from that of controls based on linkage analyses, and on their susceptibilities to the glucanohydrolases mutanase (α-1,3 hydrolase) and dextranase (α-1,6 hydrolase); soluble products from the enzymatic digestion also differed. The results show that the effects of antibody on enzyme activity are more complex than simple inhibition or enhancement and that the presence of antibody may influence glucan structure, which clearly could impact plaque formation. The results have implications for the formation and properties of biofilms formed in other environments.
Cesarean Section on Request: A Case for Common Sense
Authors: Hohlfeld Patrick
Published: April 2003

Considering the patient’s right to autonomy and the trend towards more involvement of the patient in the decision making, it is our belief that obstetricians should consider the woman’s request for cesarean section without medical indication. The procedure can only be carried out after obtaining proper consent of the patient with careful information including a detailed description of the possible risks and benefits of both modes of delivery. In order to decrease the risk of respiratory distress syndrome, cesarean section under these circumstances should not be performed prior to 39 weeks’ gestation. Debating over whether or not to charge women who request a cesarean section that is not medically indicated is fruitless, since rigorous cost studies are lacking and since any implementation of such a system would be extremely difficult.
Elektive Sectio
Authors: Husslein Peter
Published: April 2003

Im Zuge der Diskussion um die ständig steigende Sectiorate ist verstärkt auch die Frage einer elektiven Sectio nach unkomplizierter Schwangerschaft ohne Vorliegen allzu offenkundiger medizinischer Gründe für den Kaiserschnitt thematisiert worden. Aufgrund des steten Abfalls der Mortalität eines gut geplanten Kaiserschnittes und nachdem die Morbidität durch die Veränderung der Sectiotechnik ebenfalls günstig beeinflusst werden konnte, wurde der Blick naturgemäss verstärkt auf bisher weniger beachtete mütterliche und kindliche Risiken der vaginalen Geburt gerichtet. Im Zusammenhang mit der zunehmenden Bedeutung des Patientenwillens ist dadurch der Begriff der Indikation naturgemäss ins Wanken gekommen. Medizinische Indikation und Wunsch der Schwangeren sind künstliche Gegenpole – idealerweise finden sich Arzt und Patientin durch Abwägen der Vor- und Nachteile der jeweiligen Alternative zu einer gemeinsamen Entscheidung. Damit ist aber auch der Begriff «Wunsch- oder Wahlsectio» unglücklich, die dann wesentlich besser als «elektive Sectio» bezeichnet werden sollte; dabei entsteht naturgemäss auch kein ethisches Dilemma, und es gibt auch keinen Grund, warum eine medizinische Krankenversicherung die Durchführung eines solchen Eingriffes ablehnen könnte.
Differential Regulation of Insulin-Like Growth Factor-(IGF) I and IGF-Binding Protein (IGFBP) Secretion by Human Peripheral Blood Mononuclear Cells
Authors: Auernhammer C.J. , Fottner C. , Engelhardt D. , Bidlingmaier M. , Strasburger C.J. , Weber M.M.
Published: April 2003

Background: Recent studies have shown that immunocompetent cells synthesize and express growth hormone (GH), growth hormone receptors (GH-R), insulin-like growth factor I (IGF-I), IGF-I receptors (IGF-I-R) and different insulin-like growth factor binding proteins (IGFBPs). The aim of the current study was to evaluate the regulation of IGFBP and IGF-I secretion from immunocompetent cells by different mitogens. Methods/Results: We studied the in vitro secretion pattern of IGFBPs and IGF-I from human peripheral blood mononuclear cells (PBMC), derived from 10 normal adults and 8 GH-deficient patients with adult onset. In serum-free conditioned medium of unstimulated PBMC, derived from normal adults, Western ligand blotting (1D-WLB) revealed a 24-kD, a 34-kD and a 39/43-kD doublet band to be most prominent. According to their molecular weight and two-dimensional Western ligand blot analysis (2D-WLB), these bands are deglycosylated IGFBP-4, IGFBP-2 and IGFBP-3, respectively. When the cells were treated with the T-cell mitogen phytohemagglutinin (PHA) (10 µg/ml), a differential stimulation of IGFBPs was found with a 2.57 ± 0.48-fold increase of IGFBP-4 (p < 0.01), a 1.55 ± 0.13-fold increase of IGFBP-2 (p < 0.01), and a 1.35 ± 0.19-fold increase of IGFBP-3 (n.s.). In contrast, treatment with the B-cell mitogen pokeweed mitogen (PWM) (10 µg/ml) caused only a modest 1.40 ± 0.07-fold increase of IGFBP-4 (p < 0.01). Treatment with rhGH (100 ng/ml) or rhIGF-I (200 ng/ml) caused no significant induction of any specific band, respectively. In contrast to the secretion pattern of IGFBPs, IGF-I secretion of the PBMC was not stimulated by either PHA or PWM, but showed a significant increase after GH incubation (p < 0.01). A similar differentiated secretion pattern of IGFBPs and IGF-I was also observed in the conditioned medium of PBMC, derived from GH-deficient patients. Conclusion: In summary, at least three different IGFBPs are secreted by human PBMC. Secretion of IGFBPs by PBMC is differentially regulated by different lymphocyte mitogens. Secretion of IGFBPs by PBMC is independent of GH or IGF-I, whereas the secretion of IGF-I is stimulated by GH. PBMC derived from normal adults and GH-deficient patients show similar patterns of IGF-I and IGFBPs secretion, thus indicating that the paracrine/autocrine IGF-I–IGFBPs interactions of the PBMC are not altered by pituitary GH deficiency.
Assessing Insulin Resistance: Application of a Fasting Glucose to Insulin Ratio in Growth Hormone-Treated Children
Authors: Burgert Tania S. , Vuguin Patricia M. , DiMartino-Nardi Joan , Attie Kenneth M. , Saenger Paul
Published: April 2003

Background: Insulin resistance (IR) is an important risk factor for cardiovascular disease and type-2 diabetes mellitus. Therefore simple measures of IR have been proposed to screen the at-risk patient. A fasting serum glucose (mg/dl) to plasma insulin (µU/ml) ratio (FGIR) of <7 was recently suggested as a screening tool for IR in certain pediatric patients. Methods: To determine the utility of simple indicators of IR, the FGIR of <7 was applied to a group of patients with established risk for IR. The study group was comprised of non-growth hormone (GH)-deficient patients with Turner syndrome (TS, n = 92) and idiopathic short stature (ISS, n = 73) receiving GH. The occurrence of a FGIR of <7 in these cohorts was compared to data from previous publications. Results/Conclusions: The application of a FGIR of <7 confirmed a rise in IR with GH therapy in both groups as well as a higher occurrence in the TS group, rising from 22 to 48% between 12 and 24 months of GH therapy. We conclude that simple measures of IR such as the FGIR may be useful in screening and following patients at risk for IR.
Effects of Thyroid Hormone on mRNAs of Phosphoglycerate Mutase Subunits in Rat Muscle during Development
Authors: González-Cinca Núria , Gonzalo Sergio , Ascaso Carlos , Carreras José , Climent Fernando
Published: April 2003

Background: We previously showed that triiodothyronine (T3) stimulates muscle phosphoglycerate mutase (PGAM) activity and isozyme transition in rat skeletal and cardiac muscles. Methods: The effects of T3 on PGAM types B and M subunit expression in rat muscle during development are reported. Results: T3 administration during the first 21 days of rat life more than doubles type M PGAM mRNA levels, but produces minor effects on type B PGAM mRNA levels. The antihormone propylthiouracil (PTU) slightly decreases both type B and M mRNA levels, but this decrease is not statistically significant. Conclusion: Thyroid hormone influences PGAM mRNA isozyme levels differently and increases type M mRNA.
A Novel Thyroid Hormone Receptor-Beta Mutation, Not Anticipated to Occur in Resistance to Thyroid Hormone, Causes Variable Phenotypes
Authors: Catargi B. , Monsaingeon M. , Bex-Bachellerie V. , Ronci-Chaix N. , Trouette H. , Margotat A. , Tabarin A. , Beck-Peccoz P.
Published: April 2003

Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable tissue hyposensitivity to thyroid hormones and is linked to mutations in the thyroid hormone receptor-β (TRβ) gene. We report here for the first time in vivo the mutation R429W (CCG→TCG) located in the exon 10. The artificial mutant obtained in vitro displayed a normal T3-binding affinity and transactivation function. Therefore, it was thought to produce little, if any, clinical effect and to escape to clinical detection. The present report is at least in part discordant with this prediction since the propositus and his grandmother had an authentic hyperthyroidism with high FT4 plasma level in the presence of inappropriate TSH. On the other hand, spontaneous variations of clinical features and – interestingly – of plasma FT4 concentrations with time in the propositus, and the phenotype observed in his mother who never complained with thyrotoxic symptoms, confirmed the in vitro binding and functional predictions. The most intriguing is the clinical course of the grandmother as she first presented with predominant pituitary RTH and a diffuse goiter and finally with a toxic multinodular goiter with normal T3 and T4 plasma concentrations and suppressed TSH. In conclusion, we report a novel mutation in the gene encoding the thyroid hormone receptor responsible for predominant pituitary RTH already described in vitro but not in vivo. The fluctuant phenotype of the propositus suggests that other factors modulate the degree of tissue resistance that is under genetic control. Toxic multinodular goiter, possibly due to chronic TSH stimulation during RTH, in addition to the phenotype variability, increases the difficulty to diagnose this thyroid disorder.
Acetylcholine-Induced Vasodilation in the Uterine Vascular Bed of Pregnant Rats with Adriamycin-Induced Nephrosis
Authors: Yousif Mariam H. , Adeagbo Ayotunde S. , Kadavil Elizabeth A. , Chandrasekhar Bindu , Oriowo Mabayoje A.
Published: April 2003

Objective: This project was designed to study endothelium-dependent vasodilation in the uterine vascular bed during experimentally induced preeclampsia in rats. Methods: Uterine vascular beds were isolated from nonpregnant and pregnant rats with or without treatment with adriamycin (ADR) and perfused with physiological solution. Thereafter, vasodilator responses to acetylcholine were recorded. Records: Pregnant ADR-treated rats displayed symptoms of preeclampsia including hypertension and proteinuria. Blood pressure was 110.0 ± 4.7 mm Hg (n = 5) in control pregnant rats and 136.0 ± 5.3 mm Hg (n = 5) in ADR-treated pregnant rats, and urinary protein concentrations were 0.35 mg/ml (n = 5) and 13.2 ± 3.6 mg/ml (n = 9), respectively. Both blood pressure and proteinuria values were significantly (p < 0.05) different between controls and ADR-treated rats. However, acetylcholine-induced dose-dependent vasodilator responses in the vascular beds were not significantly different between the pregnant and nonpregnant rats. Although acetylcholine-induced vasodilation was significantly reduced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in both groups, the residual response to acetylcholine was not affected by indomethacin, suggesting that prostanoids were not involved in this response. The L-NAME-resistant component, endothelium-derived hyperpolarizing factor (EDHF), was greater in ADR-treated uterine beds than in those of the controls, indicating a significant contribution from EDHF in these vessels. In the presence of an elevated external potassium ion concentration, acetylcholine produced similar vasodilator responses, indicating that the release of nitric oxide was not impaired. Conclusion: These results indicate that endothelium-dependent vasodilation was not impaired in this model of preeclampsia.
α-Adrenoceptor Antagonists in the Treatment of Benign Prostate Hyperplasia
Authors: Thiyagarajan M.
Published: April 2003

Benign prostate hyperplasia (BPH) is a common malady affecting elderly men throughout the world, and it is the most common cause of voiding dysfunctions in man. The disease becomes prevalent, as the mean age of the population increases. In BPH the glandular cells and myofibroblasts of periurethral and transition zones proliferate excessively. This excessive growth of tissue mass physically compresses the urethra, leading to urinary obstruction and lower urinary tract symptoms (LUTS). Another major factor that contributes to LUTS in BPH is the increase in smooth muscle tone, a dynamic component. Contraction of the prostate gland is mainly under the control of the autonomic system and is mediated through α-adrenoceptors. In addition to α1-adrenoceptors, there are many other components that influence growth and contraction of the prostate gland, resulting in the development of BPH and LUTS. The prostate gland is contracted on stimulating 5-HT, endothelin, tachykinin, and muscarinic cholinergic receptors. Growth of the prostate gland is under the control of androgens, endothelin growth factor, vasoactive intestinal peptide, nerve growth factor, and growth hormone. The combination of excessive growth and the tone produced by different components results in LUTS and BPH. α1-Adrenoceptor antagonists were successfully used in the treatment of BPH to relieve the LUTS. The high selectivity of α1A-adrenoceptor antagonists reflects the uroselectivity. The uroselective compounds like terazosin, doxazosin, tamsulosin, and alfuzosin are in clinical use. Other new potent uroselective compounds, which are analogs of nigulidipine, 5-methyl-urapidil, or naftopidil, are in clinical trials. In addition to α-antagonists, antiandrogens (5α-reductase inhibitors) and polyherbal formulations are used to treat BPH. The success of BPH treatment lies in the development of new chemical entities which are efficacious as well as more uroselective and hence have least side effects.
Interleukin-1β-Induced Increases of Plasma Catecholamine Levels in Rats: Enhancement by Superior Cervical Ganglionectomy
Authors: Wang Muchun , Murakami Yoshinori , Okada Shoshiro , Yokotani Kunihiko
Published: April 2003

In urethane-anesthetized rats, we examined the effect of bilateral superior cervical ganglionectomy on interleukin-1β (IL-1β)-induced elevation of plasma catecholamines. In sham-operated rats, intracerebroventricularly (i.c.v.) administered IL-1β (100 ng/animal) effectively elevated plasma noradrenaline rather than plasma adrenaline. In superior cervical ganglionectomized rats, however, IL-1β significantly elevated adrenaline to a greater extent than noradrenaline, and they were attenuated by i.c.v. administration of melatonin (100 ng/animal). Superior cervical ganglionectomy effectively reduced the plasma level of melatonin and urinary excretion of 6-sulfatoxymelatonin (a main urinary melatonin metabolite). These results suggest that superior cervical ganglia inhibit central sympatho-adrenomedullary outflow (especially adrenomedullary outflow) by increasing melatonin synthesis in the pineal gland of rats.