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Showing papers by "University of Bologna published in 1995"


Journal ArticleDOI
TL;DR: A large International Restless Legs Syndrome (RLS) Study Group has been formed as discussed by the authors, which has taken upon itself the role of definig the clinical features of the RLS, including sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic from, a tendency for the symptoms to be worse in middle to older age, and a family history suggestive of an autosomal dominant mode of inheritance.
Abstract: A large International Restless Legs Syndrome (RLS) Study Group has been formed. As its first task, the group has taken upon itself the role of definig the clinical features of the RLS. As minimal criteria for diagnosis, the group proposes the following four features: (a) desire to move the extremities, often associated with paresthesias/dysesthesias; (b) motor restlessness; (c) worsening of symptoms at rest with at least temporary relief by activity, and (d) worsening of symptoms in the evening or night. Other features commonly seen in RLS include sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic from, a tendency for the symptoms to be worse in middle to older age, and, in some cases, a family history suggestive of an autosomal dominant mode of inheritance.

1,054 citations


Journal ArticleDOI
Fumio Abe, H. Akimoto1, A. Akopian2, M. G. Albrow3  +443 moreInstitutions (34)
TL;DR: In this paper, the existence of the top quark was established using a data sample of collisions at the Fermilab National Ensemble (CDF) collected with the Collider Detector.
Abstract: We establish the existence of the top quark using a $67{\mathrm{pb}}^{\ensuremath{-}1}$ data sample of $\overline{p}p$ collisions at $\sqrt{s}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1.8\mathrm{TeV}$ collected with the Collider Detector at Fermilab (CDF). Employing techniques similar to those we previously published, we observe a signal consistent with $t\overline{t}$ decay to $\mathrm{WWb}\overline{b}$, but inconsistent with the background prediction by $4.8\ensuremath{\sigma}$. Additional evidence for the top quark is provided by a peak in the reconstructed mass distribution. We measure the top quark mass to be $176\ifmmode\pm\else\textpm\fi{}8(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}10(\mathrm{syst})\mathrm{GeV}{/c}^{2}$, and the $t\overline{t}$ production cross section to be ${6.8}_{\ensuremath{-}2.4}^{+3.6}\mathrm{pb}$.

1,022 citations


Journal ArticleDOI
TL;DR: The incidence of death or severe congestive heart failure at six weeks was significantly reduced in the zofenopril group, as compared with the placebo group, which was reexamined after one year to assess survival.
Abstract: Background Left ventricular dilatation and neuroendocrine activation are common after acute anterior myocardial infarction. Long-term treatment with an angiotensin-converting–enzyme (ACE) inhibitor may improve outcome by attenuating these processes. We investigated whether the ACE inhibitor zofenopril, administered for six weeks after anterior myocardial infarction, could improve both short-term and long-term outcome. Methods A total of 1556 patients were enrolled within 24 hours after the onset of symptoms of acute anterior myocardial infarction, and they were randomly assigned in a double-blind fashion to receive either placebo (784 patients) or zofenopril (772 patients) for six weeks. At this time we assessed the incidence of death or severe congestive heart failure. The patients were reexamined after one year to assess survival. Results The incidence of death or severe congestive heart failure at six weeks was significantly reduced in the zofenopril group (55 patients, 7.1 percent), as compared with t...

728 citations


Book ChapterDOI
TL;DR: Strichartz inequalities for the wave equation are estimates of the solution u of the Cauchy problem for that equation, in the form of space-time integral norms, in terms of similar norms of the inhomogeneity f and of suitable norm of the initial data.

556 citations


Journal Article
TL;DR: The increased binding of TEC-11 to tumor vasculature and to dividing as opposed to noncycling HUVECs in vitro suggests that endoglin is an endothelial cell proliferation-associated marker, which might have therapeutic value in the treatment of solid tumors in humans.
Abstract: We have characterized a murine IgM monoclonal antibody, TEC-11, that recognizes endoglin and may be suitable for targeting cytotoxic agents to human tumor vasculature. TEC-11 strongly stains endothelial cells in a broad range of solid human tumors while staining endothelial cells in the majority of normal, healthy adult tissues relatively weakly. Human umbilical vein endothelial cells (HUVECs) in sections of the umbilical vein react weakly with TEC-11, whereas proliferating HUVECs in tissue culture react strongly and uniformly. HUVEC cultures grown to confluence and then rested contain two subpopulations having high and low levels of endoglin expression. Flow cytometry revealed that a significant proportion of cells with high endoglin expression are cycling, having markedly increased levels of cellular protein, RNA, and DNA by comparison to low endoglin-expressing cells, which appear to be noncycling. Taken together, the increased binding of TEC-11 to tumor vasculature and to dividing as opposed to noncycling HUVECs in vitro suggests that endoglin is an endothelial cell proliferation-associated marker. An immunotoxin [TEC-11.deglycosylated ricin A chain (dgA)] composed of TEC-11 and dgA was 3000-fold more potent at inhibiting protein synthesis in proliferating HUVEC cultures than in confluent cultures. The confluent cells were no more sensitive to TEC-11.dgA than they were to an isotype-matched immunotoxin of irrelevant specificity. These findings suggest that TEC-11.dgA might have therapeutic value in the treatment of solid tumors in humans by selectively killing dividing endothelial cells which are prevalent in such tumors.

357 citations



Journal ArticleDOI
TL;DR: This work provides a process algebra similar to CCS with a set of security notions, hence relating these two areas of concurrency research and showing that some of these security properties are composable w.r.t. the operators of parallelism and action restriction.
Abstract: Several information flow security definitions, proposed in the literature, are generalized and adapted to the model of labelled transition systems. This very general model has been widely used as a semantic domain for many process algebras, e.g. CCS. As a by-product, we provide a process algebra similar to CCS with a set of security notions, hence relating these two areas of concurrency research. A classification of these generalized security definitions is presented, taking into account also the additional property of input totality, which can influence this taxonomy. We also show that some of these security properties are composable w.r.t. the operators of parallelism and action restriction.

317 citations


Journal ArticleDOI
TL;DR: In this article, a short review compares different technologies for the synthesis of styrene which are currently studied as alternatives to the industrial dehydrogenation of ethylbenzene: de-deprivation of the polyethylene, followed by oxidation of hydrogen, catalytic and stoichiometric oxidative de-decoupling, and dehydrogenization in membrane reactors.
Abstract: This short review compares different technologies for the synthesis of styrene which are currently studied as alternatives to the industrial dehydrogenation of ethylbenzene: dehydrogenation of ethyl-benzene followed by oxidation of hydrogen, catalytic and stoichiometric oxidative dehydrogenation of ethylbenzene, and dehydrogenation in membrane reactors. The advantages and drawbacks of each technology are illustrated and discussed, and the catalytic systems employed are described.

309 citations


Journal ArticleDOI
26 Oct 1995-Nature
TL;DR: In this article, the authors report observations obtained with the Hubble Space Telescope of two metal-rich globular clusters that form part of the bulge population, and they appear to be coeval with halo clusters.
Abstract: THE morphology of our Galaxy is characterized by a disk of stars moving on circular orbits, surrounding a central spheroidal body of stars on high-velocity, randomly oriented orbits. The spheroid is further differentiated into an inner bulge and an outer halo; the bulge stars are rich in elements heavier than helium ('metals'), whereas the halo stars are metal-poor, suggesting that the latter formed very early in the history of the Galaxy. (They have experienced little chemical enrichment, by previous generations of stars.) It is not known, however, whether the bulge is the inner extension of the halo, having formed as part of the same process1, or whether it formed much later, perhaps by a dynamical distortion of the inner regions of the disk2,3. Here we report observations obtained with the Hubble Space Telescope of two metal-rich globular clusters that form part of the bulge population. Within the uncertainties, these bulge globular clusters appear to be coeval with halo clusters, which suggests that the formation of the bulge was part of the dynamical process that formed the halo, and that the bulge gas underwent rapid chemical enrichment, in less than a few billion years.

308 citations


Journal Article
16 Feb 1995-Oncogene
TL;DR: Activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas.
Abstract: The c-MET oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor (HGF), a cytokine that stimulates the invasive growth of normal and neoplastic cells. The Met/HGF receptor is expressed by epithelial cells and its ligand by cells of mesenchymal origin. Receptor-ligand interaction occurs via a paracrine circuit. We studied the expression of the Met/HGF receptor and of its ligand in mesenchymal human tumours by examining 39 clinical samples of bone tumours. The Met/HGF receptor was not detectable in the majority of bone tumours, as expected from their mesenchymal origin. Notably, the receptor was overexpressed in 60% of the osteosarcomas examined. In 12 osteosarcoma cell lines the Met/HGF receptor was overexpressed, phosphorylated by HGF stimulation and fully functional. HGF was detected in two out of seven clinical specimens of osteosarcoma. The ligand and the receptor are co-expressed in two clonal osteosarcoma cell lines. In these lines the Met/HGF receptor was constitutively phosphorylated; phosphorylation was suppressed by suramin treatment, a known blocker of autocrine loops. These data suggest that activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas.

299 citations


Journal ArticleDOI
TL;DR: The results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.

Journal ArticleDOI
TL;DR: Surgery and percutaneous ethanol injection improve survival in single hepatocellular carcinoma associated with Child A and B cirrhosis compared to untreated patients in the same Child class.

Journal ArticleDOI
TL;DR: The presence in area PO (V6) of real‐position cells together with a high percentage of eye position‐sensitive neurons, most of them visual in nature, suggests that this cortical area is engaged in the spatial encoding of extrapersonal visual space.
Abstract: The aim of this work was to study the effect of eye position on the activity of neurons of area PO (V6), a cortical region located in the most posterior part of the superior parietal lobule. Experiments were carried out on three awake macaque monkeys. Animals sat in a primate chair in front of a large screen, and fixated a small spot of light projected in different screen locations while the activity of single neurons was extracellularly recorded. Both visual and non-visual neurons were found. About 48% of visual and 32% of non-visual neurons showed eye position-related activity in total darkness, while in approximately 61% of visual response was modulated by eye position in the orbit. Eye position fields and/or gain fields were different from cell to cell, going from large and quite planar fields up to peak-shaped fields localized in more or less restricted regions of the animal's field of view. The spatial distribution of fixation point locations evoking peak activity in the eye position-sensitive population did not show any evident laterality effect, or significant top/bottom asymmetry. Moreover, the cortical distribution of eye position-sensitive neurons was quite uniform all over the cortical region studied, suggesting the absence of segregation for this property within area PO (V6). In the great majority of visual neurons, the receptive field 'moved' with gaze according to eye displacements, remaining at the same retinotopic coordinates, as is usual for visual neurons. In some cases, the receptive field did not move with gaze, remaining anchored to the same spatial location regardless of eye movements ('real-position cells'). A model is proposed suggesting how eye position-sensitive visual neurons might build up real-position cells in local networks within area PO (V6). The presence in area PO (V6) of real-position cells together with a high percentage of eye position-sensitive neurons, most of them visual in nature, suggests that this cortical area is engaged in the spatial encoding of extrapersonal visual space. Since lesions of the superior parietal lobule in humans produce deficits in visual localization of targets as well as in arm-reaching for them, and taking into account that the monkey's area PO (V6) is reported to be connected with the premotor area 6, we suggest that area PO (V6) supplies the premotor cortex with the visuo-spatial information required for the visual control of arm-reaching movements.

Journal ArticleDOI
TL;DR: In this paper, a detailed analysis of recent literature on glaucony and selected case studies (Eocene, Isle of Wight; Miocene, northern Apennines) shows that the presence of glauconsy alone is not diagnostic of a specific systems tract of a depositional sequence.
Abstract: Detailed analysis of recent literature on glaucony and selected case studies (Eocene, Isle of Wight; Miocene, northern Apennines) shows that the presence of glaucony alone is not diagnostic of a specific systems tract of a depositional sequence. A reliable sequence stratigraphic interpretation of glaucony-bearing units requires additional information on glaucony, including: (1) spatial distribution, (2) maturity (distinction between nascent, slightly evolved, evolved, and highly evolved glaucony), and (3) genetic attributes (differentiation of autochtonous from allochthonous, and intrasequential from extrasequential glaucony). Autochthonous glaucony is common at various stratigraphic levels in the transgressive systems tract (TST) and the lower highstand systems tract (HST), showing an upward increase (TST) and then decrease (HST) in abundance and maturity. The condensed section can be distinguished from the overlying and underlying deposits by the higher concentration and maturity of glaucony. Allochthonous intrasequential (parautochthonous) glaucony can be present in the entire TST, HST, and lowstand systems tract (LST), generally showing lower concentration and maturity than its autochthonous counterpart. Allochthonous extrasequential (detrital) glaucony is present mainly in the LST, its concentration and composition depending on the characteristics of the source horizon. The associa ion between autochthonous and allochthonous (intrasequential and extrasequential) glaucony commonly exists in the LST and in the lower TST.

Journal ArticleDOI
TL;DR: Results in treated patients suggest that gluten-free diet improves but does not normalize BMD, which is almost invariably low in patients with untreated celiac disease.

Journal ArticleDOI
TL;DR: C3 levels measured in sera from male subjects without previous ischemic events are independently associated with the risk of MI, and a separate analysis for the sexes showed that serum C3 was a particularly powerful predictor of MI in men.

Journal ArticleDOI
TL;DR: Pretreatment of human ramified microglial cells with nearly physiological levels of exogenous NO prevents lipopolysaccharide (LPS)/tumor necrosis factor α (TNFα)-inducible NO synthesis, because by affecting NF-κB activation it inhibits inducible Ca-independent NO synthase isoform (iNOS) mRNA expression.

Journal Article
TL;DR: It is ascertained that the condition associated with D. repens is the most frequent and the most widely distributed in the world, of the dirofilariases of medical relevance: comprehensively 397 cases were recorded in 30 countries, exclusively in the Old World, with endemic foci in Southern and Eastern Europe, Central Asia and Sri Lanka.
Abstract: For some Dirofilaria spp. of zoonotic importance, such as D.immitis, D.tenuis, D.ursi, reviews of human cases were often published. For D. repens there is no published information giving a picture of the importance of the problem and of the geographical distribution of the parasite in the world. From a study of the international literature and from direct experience (our workgroup observed 75 cases in Italy) we have ascertained that the condition associated with D. repens is the most frequent and the most widely distributed in the world, of the dirofilariases of medical relevance: comprehensively 397 cases were recorded in 30 countries, exclusively in the Old World, with endemic foci in Southern and Eastern Europe, Asia Minor, Central Asia and Sri Lanka. Apparently, the most affected country is Italy with a total of 168 cases. The most common localisations are the subcutaneous (normally nodular) and the submucosal (nodular or not). The most affected areas are the head, the thoracic wall and the upper limbs. However, 15 cases with internal localisations are recorded (9 of them being pulmonary) which were always diagnosed erroneously as malignant neoplasiae. Clinical diagnosis for the other localisations was also generally wrong with the exception of the subconjunctival cases, where because of the transparency of the bulbar conjunctiva, it is possible to see the parasite directly. The correct diagnosis is usually histological, based on the identification of the nematode using the morphological characters of the species to differentiate it from the other dirofilariae or other erratic nematodes. It is possible that the zoonosis in man is more frequent than shown by the literature: many cases are not diagnosed, viz. not published, others recover spontaneously without medical intervention.

Journal ArticleDOI
TL;DR: The higher incidence of epilepsy and EEG PA is apparently not related to organic pre-, peri- and postnatal antecedents or cerebral lesions, and genetic factors responsible for autism and epilepsy seem important in the genesis of these two disorders.
Abstract: Epileptic seizures are frequently reported (4-32%) in autism. These values are higher than in the normal population of children and adolescents (0.5%). In the literature there is no uniform description of epilepsy in autism. We examined 106 patients with autistic disorder divided into three groups on the basis of presence or absence of EEG paroxysmal abnormalities (PA) and / or epilepsy including febrile convulsions (FG). Our patients presented an autistic syndrome unrelated to clear congenital or acquired encephalopathy. The prevalence of epilepsy and EEG PA was 23.6% and 18.9%, respectively. Significant differences between the three groups appeared for (i) familial antecedents for epilepsy / FC and neurologic and psychiatric diseases (P < 0.004), (ii) a different proportion between the three groups for mental retardation (P < 0.03), (iii) and EEG fast activity (P < 0.04). Our patients showed several types of epilepsy, including idiopathic forms with seizure onset after the age of 10 in 45% of cases. Seizures were mainly partial, not frequent and controllable by anti-epileptic drugs. PA were mostly focal and multifocal and in 45% of cases were typical of benign childhood partial epilepsy with centro-temporal spikes. The higher incidence of epilepsy and EEG PA is apparently not related to organic pre-, peri- and postnatal antecedents or cerebral lesions. On the contrary, genetic factors responsible for autism and epilepsy seem important in the genesis of these two disorders.

Journal ArticleDOI
01 Apr 1995
TL;DR: The goals of this study can be articulated in four points: to enumerate the degrees of freedom of the manipulation system; to describe analytically all possible first-order differential motions of the system at a given configuration; to evaluate in the velocity domain the functionality of a manipulation system, with respect to the task it is required to perform; and to calculate the bounds for the velocities achievable by the system, given bounds on the capabilities of joint actuators.
Abstract: In this paper, the analysis of the differential kinematics and manipulability measures of robotic systems comprised of multiple cooperating limbs is considered. The goals of this study can be articulated in four points: 1) to enumerate the degrees of freedom of the manipulation system; 2) to describe analytically all possible first-order differential motions of the system at a given configuration; 3) to evaluate in the velocity domain the functionality of a manipulation system, with respect to the task it is required to perform; and 4) to calculate the bounds for the velocities achievable by the system, given bounds on the capabilities of joint actuators. The assumptions made on the robotic system are quite general, so that many complex devices (e.g., dextrous hands, legged vehicles, whole-arm manipulators, etc.) can be dealt with in a unified and convenient framework. >

Journal ArticleDOI
TL;DR: This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.

Journal ArticleDOI
TL;DR: Coeliac disease is a frequent cause of iron-deficiency anaemia, and antigliadin and antiendomysial antibody tests should be always performed in the diagnostic algorithm of anaemic patients.
Abstract: Background: Although it is known that anaemia may be the only presenting symptom in coeliac disease, prevalence figures of unsuspected coeliac disease in anaemic patients are not available. The aim of this study was to assess the clinical usefulness of antigliadin and antiendomysial antibody tests in the diagnostic algorithm of anaemic patients. Methods: Two hundred consecutive anaemic patients were tested for antigliadin antibodies, and those positive were also tested for antiendomysial antibodies. All patients positive for antigliadin and antiendomysial antibodies underwent intestinal biopsy. Results: Sixteen patients were antigliadin antibody-positive, and 10 were also antiendomysial antibody-positive. In all 10 a jejunal biopsy was consistent with coeliac disease (prevalence, 5%). This prevalence rose to 8.5% when patients with macrocytic anaemia or with microcytic anaemia due to previous bleeding or responsive to oral iron therapy were excluded from the calculation. Conclusions: Coeliac disease is a ...

Journal ArticleDOI
TL;DR: R Reed-Sternberg cells with B-cell phenotypes have rearranged VH genes; therefore, these cells arise from B cells and correlation with the clinical stage suggests that polyclonal Hodgkin's disease can present as a widespread lymphoma.
Abstract: Background There is strong evidence that Reed–Sternberg cells have a lymphoid phenotype, but clonally rearranged genes for B-cell and T-cell antigen receptors have not been demonstrable in tumor tissue from most patients with Hodgkin's disease. To elucidate this issue, we assayed single Reed–Sternberg cells from 12 patients with classic Hodgkin's disease of a B-cell immunophenotype to detect rearranged immunoglobulin variable-region heavy-chain (Vh) genes. Methods We isolated single Reed–Sternberg cells from frozen sections that had been immunostained for CD30. The rearranged Vh genes of these cells were amplified by the polymerase chain reaction and analyzed by gel electrophoresis and nucleotide sequencing. Results In all 12 patients, the Reed–Sternberg cells studied contained rearranged Vh genes. Three patterns were observed: in three patients the rearrangements in each patient were identical, in six patients all the rearrangements were unrelated and unique, and in three patients both identical and unre...

Journal Article
TL;DR: Both the CTL activity and the Ab responses induced by IL-10 high producer cells are the strongest so far observed in the TSA system.
Abstract: The cDNA coding for mouse IL-10 (mIL-10) was transduced into the parental cells of a spontaneous adenocarcinoma of BALB/c mice (TSA-pc), and clones secreting small, medium, and large quantities of IL-10 were selected In vivo, both low and high producer clones do not display an enhanced ability to grow in H-2 and non-H-2 incompatible mice Instead, the intensity of their rejection increases in function of the amount of mIL-10 released After an initial growth period in syngeneic mice, high producer clones undergo complete rejection due to the combined action of CD8+ lymphocytes, NK cells, and neutrophils After this rejection, mice are immune to a subsequent challenge with TSA-pc This memory rests on a strong lytic activity of CD8+ CTL and granulocytes Following the rejection, mice also develop anti-TSA Ab that guide the granulocytes in TSA-pc memory reaction A direct comparison shows that although TSA clones engineered to release IL-2 activate CTL and no anti-TSA Ab, those engineered to release IL-4 activate a strong Ab response but not CTL The kind of cytokine released by the tumors appears to determine the type of response However, IL-10 high producer cells do not deviate the immune memory, neither toward a Th1 nor a Th2 Both the CTL activity and the Ab responses induced by IL-10 high producer cells are the strongest so far observed in the TSA system

Journal ArticleDOI
TL;DR: The analysis of the FF intervals demonstrates a strict correlation with atrial functional refractoriness, which is consistent with the presence of a gap of excitability during atrial fibrillation in the human atria.
Abstract: Background The aims of our study were to investigate the meaning of local atrial activation and its behavior during paroxysmal atrial fibrillation and to study the effect of overdrive pacing on local atrial activity. Methods and Results Twenty-five patients with lone paroxysmal atrial fibrillation underwent electrophysiological study. Functional and effective atrial refractoriness was determined. Mean and fifth percentile values of 100 consecutive atrial fibrillation intervals (FF) were evaluated at three atrial sites either at arrhythmia onset or at self-termination (or at minute 5). A high-voltage burst pacing was performed after 6 minutes of stable atrial fibrillation in 10 patients. Mean FF intervals were evaluated 5 seconds before and after atrial pacing. Forty-nine atrial fibrillation episodes were induced: 39 self-terminating within 5 minutes and 10 long-lasting. A significant correlation was found between mean FF and atrial functional refractory period (r=.73, P<.001) and between fifth percentile ...


Journal ArticleDOI
TL;DR: In this paper, the role of zinc on hydroxylapatite (HA) crystallization was investigated using X-ray diffraction and spectrophotometric analysis, showing that zinc cannot substitute for calcium in HA structure.

Journal ArticleDOI
TL;DR: Assessment of echo‐Doppler measurements of portral blood flow velocity (PBV), portal vein diameters (PVDs) and their derived parameters, portal blood flow (PBF), and congestion index (CI) in cirrhotic patients indicates that a significant systematic vaiability exists between Dopplers measurements with different equipment and a cooperative training program reduces the interobserver variability for direct measurements, such as PBV.

Journal ArticleDOI
TL;DR: Post-hatching growth of lateral muscle in a teleost fish, Sparus aurata was studied morphometrically to identify and quantify muscle fibre hyperplasia and hypertrophy, and by in vivo nuclear labelling with 5-bromo-deoxyuridine to identify areas of myoblast proliferation.
Abstract: Post-hatching growth of lateral muscle in a teleost fish, Sparus aurata (L) was studied morphometrically to identify and quantify muscle fibre hyperplasia and hypertrophy, and by in vivo nuclear labelling with 5-bromo-deoxyuridine to identify areas of myoblast proliferation. Muscle fibre types were identified principally by myosin ATPase histochemistry and immunostaining, and labelled nuclei were identified at light and electronmicroscope level by immunostaining with a specific monoclonal antibody. Hyperplastic growth was slow at hatching, but then increased to a maximum at the mid-point of larval life. Larval hyperplastic growth occured by apposition of new fibres along proliferation zones, principally just under the lateral line and in the apical regions of the myotome, but also just under the superficial monolayer at intermediate positions. The first of these zones gave rise to slow and pink muscle fibres, in a process which continued through into postlarval life. The other zones added new fibres to the fast-white muscle layer in a process which was exhausted by the end of larval life. Post-larvally, between 60 and 90 days posthatching, a new hyperplastic process started in the fast-white muscle as nuclei proliferated and new muscle fibres were formed throughout the whole layer. This process resulted in a several-fold increase in the number of fast-white fibres over a few weeks, and then waned to very low levels in juveniles. Hyperplasia by apposition continued for some time postlarvally on the deep surface of the superficial monolayer, but at this stage gave rise to slow fibres only. Hypertrophic growth occurred at all ages, but was the dominant mechanism of muscle growth only in the juvenile and adult stages. Mechanisms giving rise to these different growth processes in fish muscle are discussed, and compared with muscle development in higher vertebrates.

Journal ArticleDOI
TL;DR: Findings indicate that in fatal familial insomnia, the pathological phenotype is the result of the variability, in different brain regions, of the timing and rate of accumulation of protease‐resistant prion protein, and (2) vulnerability to the presence of prote enzyme‐resistantPrion protein.
Abstract: Protease-resistant prion protein, total prion protein, and glial fibrillary acidic protein were measured in various brain regions from 9 subjects with fatal familial insomnia. Six were homozygotes methionine/methionine at codon 129 (mean duration, 10.7 ± 4 months) and 3 were heterozygotes methionine/valine (mean duration, 23 ± 11 months). In all subjects, protease-resistant prion protein was detected in gray mattet but not in white matter and peripheral organs. Its distribution was more widespread than that of the histopathological lesions, which were observed only in the presence of a critical amount of the abnormal protein. In the mediodorsal thalamic nucleus, however, a severe neuronal loss and astrogliosis were associated with relatively moderate amounts of protease-resistant prion protein, suggesting a higher vulnerability. There was no overall correlation between amount of protease-resistant prion protein and either glial fibrillary acidic protein or total prion protein. While protease-resistant prion protein was virtually limited to subcortical areas and showed a selective pattern of distribution in the subjects with disease of the shortest duration, it was more widespread in the subjects with a longer clinical course, indicating that with time the disease process spreads within the brain. The kinetics of the accumulation of protease-resistant prion protein varied among different brain regions : While in the neocortex and to a lesser extent in the limbic lobe and in the caudate nucleus, the amount increased with disease duration, in the mediodorsal thalamic nucleus and in the brainstem it was present in comparable amounts in all subjects regardless of the disease duration. These findings indicate that in fatal familial insomnia, the pathological phenotype is the result of the variability, in different brain regions, of the (1) timing and rate of accumulation of protease-resistant prion protein, and (2) vulnerability to the presence of protease-resistant prion protein.