Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of the Putamen/Caudate Volume Ratio for Early Differentiation between Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease

Background and purpose Neuropathological studies have demonstrated that multiple system atrophy (MSA) produces selective atrophy of the putamen with sparing of the caudate nucleus, while both structures are spared in idiopathic Parkinson's disease (PD). In this study we evaluated the clinical efficacy of using putaminal atrophy in brain MRI to differentiate MSA and PD. Methods We measured the putamen/caudate volume ratio on brain MRI in 24 patients with MSA and 21 patients with PD. Two clinicians who were blinded to the patients' diagnoses and to each other's assessments measured the volume ratio using a computer program. Results The measured volume ratios of the two investigators were highly correlated (r=0.72, p<0.0001). The volume ratio was significantly lower in MSA (1.29±0.28) than PD (1.91±0.29, p<0.0001). Setting an arbitrary cutoff ratio of 1.6 resulted in about 90% of patients with MSA falling into the group with a lower ratio, whereas more than 80% of patients with PD belonged to the other group. Conclusions The present results demonstrate that putaminal atrophy in MSA as measured on brain MRI represents an effective tool for differentiating MSA from PD.
Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy.

BACKGROUND Familial hypertrophic cardiomyopathy is characterized by a variable degree of myocardial hypertrophy and a wide range of symptoms. Different mutations in the beta cardiac myosin heavy-chain gene have been identified in three affected families. However, neither the proportion of cases attributable to myosin mutations nor the effects of different mutations on clinical outcome are known. METHODS Using a ribonuclease protection assay, we screened the beta cardiac myosin heavy-chain genes of probands from 25 unrelated families with familial hypertrophic cardiomyopathy; this assay is a sensitive method for detecting the presence and location of mutations. We further defined the mutations by analyzing their nucleotide sequences. The clinical features of the disease were compared in families with various myosin mutations. RESULTS Seven mutations in the beta cardiac myosin heavy-chain gene were identified in 12 of the 25 families. All were missense mutations (i.e., causing the substitution of a single amino acid) clustered in the head and head-rod junction regions of the molecule. Six mutations resulted in a change in the charge of the amino acid. Patients with mutations that changed the charge of the altered amino acid (such as that from arginine to glutamine at nucleotide 403 or from arginine to cysteine at nucleotide 453) had a significantly shorter life expectancy (mean age at death, 33 years), whereas patients with the one mutation that did not produce a change in charge (Val606Met) had nearly normal survival. However, patients with different mutations did not differ appreciably in their clinical manifestations of familial hypertrophic cardiomyopathy. CONCLUSIONS Different missense mutations in the beta cardiac myosin heavy-chain gene can be identified in approximately 50 percent of families with hypertrophic cardiomyopathy. In those families, a definite genetic diagnosis can be made in all members. Since the location of a mutation or its DNA-sequence alteration (or both) appears to influence survival, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members.
HISTOCHEMICAL STUDIES OF NEPHROTOXICITY WITH SUBLETHAL DOSES OF MERCURY IN RATS.

son 2reviewed the phenomenon, as it has been studied with classic histologic techniques. Histochemical features have also been investigated in the rat and other mammals by Wachstein and Meisel9 and others 2A,1012 utilizing mainly lethal doses of mercurial diuretics or mercuric chloride. Only a few investigators have employed sublethal doses of mercury, examining lesions by conventional paraffin-embedded sections, autoradiography7" 3 and "physical" methods 14 for direct detection of mercuric ions in tissue. In this study graded sublethal doses of mercuric chloride were employed with the object of inducing subtle renal lesions and of demonstrating significant histochemical changes prior to the appearance of early degenerative changes and coagulative necrosis as visualized in hematoxylin and eosin sections. In addition, we hoped to show that some of the changes could be detected in cells with reversible alterations.
Head Direction Cell Activity Is Absent in Mice without the Horizontal Semicircular Canals

Head direction (HD) cells fire when an animal faces a particular direction in its environment, and they are thought to represent the neural correlate of the animal's perceived spatial orientation. Previous studies have shown that vestibular information is critical for generating the HD signal but have not delineated whether information from all three semicircular canals or just the horizontal canals, which are primarily sensitive to angular head rotation in the horizontal (yaw) plane, are critical for the signal. Here, we monitored cell activity in the anterodorsal thalamus (ADN), an area known to contain HD cells, in epstatic circler (Ecl) mice, which have a bilateral malformation of the horizontal (lateral) semicircular canals. Ecl mice and their littermates that did not express the mutation (controls) were implanted with recording electrodes in the ADN. Results confirm the important role the horizontal canals play in forming the HD signal. Although normal HD cell activity (Raleigh's r > 0.4) was recorded in control mice, no such activity was found in Ecl mice, although some cells had activity that was mildly modulated by HD (0.4 > r > 0.2). Importantly, we also observed activity in Ecl mice that was best characterized as bursty—a pattern of activity similar to an HD signal but without any preferred firing direction. These results suggest that the neural structure for the HD network remains intact in Ecl mice, but the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable HD signal. SIGNIFICANCE STATEMENT Cells in the anterior dorsal thalamic nucleus normally fire in relation to the animal's directional heading with respect to the environment—so-called head direction cells. To understand how these head direction cells generate their activity, we recorded single-unit activity from the anterior dorsal thalamus in transgenic mice that lack functional horizontal semicircular canals. We show that the neural network for the head direction signal remains intact in these mice, but that the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable head direction signal.
Effect of hypoglycemia on thermoregulatory responses.

The effects of hypoglycemia on sweating, skin blood perfusion, and shivering responses were investigated in 10 healthy male volunteers. They exercised on an underwater cycle ergometer while immersed to the neck in 28 degrees C water for 20 min at 50% of their maximal work rate. The exercise-induced elevation in esophageal temperature (T(es)) initiated the sweating response (Esw) and increased skin blood perfusion (SkBP) as measured at the forehead. In the 99-min postexercise immersion period, the values of T es relative to resting level (delta T(es)) at which Esw abated, SkBP reached preexercise values, and shivering commenced were defined as the delta T(es) thresholds for cessation of sweating, passive vasodilation, and onset of shivering, respectively. Two trials were conducted 1 wk apart. The subject was hypoglycemic in one trial and euglycemic in the other (plasma glucose was maintained at 2.8 and 5 mM, respectively) with the use of the hyperinsulinemic (insulin infusion rate = 60 mU.m-2.min-1) glucose-clamp technique. Oxygen uptake, Esw, T(es), mean skin temperature, heat flux from the skin, and SkBP were recorded at minute intervals. Although heat flux and SkBP attained significantly higher end-exercise levels during euglycemia, the responses were similar during the postexercise cooling period. Hypoglycemia did not affect the Esw response during the exercise and cooling periods. Whereas the exercise delta T(es) response was unaffected by hypoglycemia, the decrease in T(es) was greater (P < or = 0.005) during the hypoglycemic than during the euglycemic condition. Hypoglycemia did not alter the delta T(es) threshold for cessation of sweating and passive vasodilation but reduced (P < or = 0.001) the delta T(es) threshold for onset of shivering (from -0.09 +/- 0.07 degrees C in the euglycemic condition to -0.65 +/- 0.12 degrees C in the hypoglycemic condition). The present results indicate that hypoglycemia (2.8 mM) does not affect the delta T(es) threshold for cessation of thermoregulatory sweating or the threshold for passive vasodilation during recovery from exercise-induced moderate heat stress but that it decreases the core temperature threshold for shivering during cold exposure.
Domains in the simian immunodeficiency virus gp41 cytoplasmic tail required for envelope incorporation into particles.

The mechanism by which lentivirus envelope (Env) glycoproteins are packaged into budding virions is poorly understood. Simian immunodeficiency virus (SIV) contains an Env protein with an unusually long cytoplasmic tail. To investigate the role of this domain in the incorporation of the SIV Env into virions, we generated a series of SIV Env mutants carrying small in-frame deletions within the cytoplasmic domain. The effects of these mutations on Env synthesis, processing, and association with Gag particles were analyzed by means of the vaccinia virus expression system. All of the mutant Env glycoproteins were synthesized and processed in a manner similar to that of the wild-type Env. However, deletions affecting domains C-terminal to residue 832 in the SIV Env protein significantly impaired Env incorporation into particles. Cell surface biotinylation assays showed that this phenotype could not be attributed to inefficient cell surface expression of the Env mutants. Furthermore, when the Env deletion mutants were tested for their ability to mediate virus entry in single-cycle infectivity assays, those mutations that impaired Env incorporation also caused a severe defect in virus infectivity. Our results suggest that domains in the C-terminal third of the SIV Env protein are required for Env incorporation into particles and Env-mediated virus entry.
p16 Inactivation in Pancreatic Intraepithelial Neoplasias (PanINs) Arising in Patients With Chronic Pancreatitis

Patients with long-standing chronic pancreatitis are thought to be at increased risk of developing pancreatic ductal adenocarcinoma, but the mechanism for this increased risk is unknown. Since increasing evidence supports the notion that infiltrating pancreatic ductal adenocarcinomas arise from pancreatic intraepithelial lesions (PanINs), we sought to determine if patients with chronic pancreatitis harbor PanINs with alterations in tumor suppressor genes that are associated with infiltrating pancreatic ductal adenocarcinoma. We identified 122 patients with a diagnosis of chronic pancreatitis and 29 patients with a well-differentiated pancreatic endocrine tumor that underwent pancreatic surgery at the Johns Hopkins Hospital from 1985 to 1999. PanINs from each resection specimen were identified, graded, counted, and correlated with smoking and alcohol history. The expression patterns of p16 and Smad4 were determined in a subset of PanINs by immunohistochemistry, and the pattern of labeling compared with that seen in PanINs associated with infiltrating adenocarcinoma of the pancreas as identified in prior studies, and to PanINs associated with pancreatic endocrine tumor. Duct lesions were present in 80 of the 122 pancreata with chronic pancreatitis (66%). Of 405 duct lesions identified in the chronic pancreatitis group, 7.6% were reactive changes, 65.5% were PanIN-1A, 18% were PanIN-1B, 7.4% were PanIN-2, and 1.5% were PanIN-3. Within the pancreatic endocrine tumor group, 22 PanINs were identified: 15 PanIN-1A, 4 PanIN-1B, and 3 PanIN-2. There were significantly fewer high-grade PanINs in the pancreata with chronic pancreatitis than in pancreata with pancreatic adenocarcinoma (P < 0.0001). Within the chronic pancreatitis group, the 80 patients with PanINs were significantly older than the 42 patients without PanINs (mean age 57.0 ± 14.1 years vs. 50.9 ± 14.7 years, P = 0.01). Smoking history was not associated with PanIN prevalence or grade, but patients who reported a history of excessive alcohol consumption had fewer PanINs (25 of 44 harbored PanINs, 57%) than those who did not (54 of 74, 73%, P = 0.07). In the chronic pancreatitis group, 0% of PanIN-1A, 11% of the PanIN-1B, 16% of the PanIN-2, and 40% of the PanIN-3 lesions showed loss of p16 expression, whereas all of the PanINs from patients with an pancreatic endocrine tumor retained p16 expression. All of the PanINs analyzed from patients with chronic pancreatitis retained normal Smad4 expression. We conclude that a significant minority of PanINs arising in patients with chronic pancreatitis show loss of p16 expression. This alteration, common to pancreatic cancer-associated PanINs, may contribute to the predisposition of patients with chronic pancreatitis to develop pancreatic ductal adenocarcinoma.
Dynamic Electrothermal Model of Paralleled IGBT Modules With Unbalanced Stray Parameters

Compared with single-module applications, unbalanced stray parameters come about frequently in the process of installing paralleled IGBT modules, which could result in some distinctions of current sharing and temperature distributions. To focusing on depicting this practical issue, a novel dynamic electrothermal model extended to paralleled systems is proposed in this paper to establish a comprehensive transient model to characterize the relations of power losses, junction temperature, and unbalanced parasitic elements. The model can describe the interactions of current distributions and thermal dissipations between paralleled modules. In addition, the variation of unbalanced temperature during transient process can be obtained with the proposed electrothermal model. First, the stray inductance parameters in the paralleled branches are analyzed in detail by finite-element-method simulation tool. And based on impedance analysis, an improved power loss model is built up, considering the interaction of paralleled devices. Moreover, by the method of resistor-capacitor networks extracted from numerical simulations of 3-D structural model, the transient thermal impedance of devices and cooling system is obtained for fast and accurate electrothermal cosimulation of the paralleled system. Experimental results are carried out to verify the proposed model and coincide with the theoretical analysis.
Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery.

BACKGROUND Propofol and sevoflurane are suitable agents for maintenance of anaesthesia during neurosurgical procedures. We have prospectively compared these agents in combination with the short-acting opioid, remifentanil. METHODS Fifty unpremedicated patients undergoing elective craniotomy received remifentanil 1 microg kg(-1) followed by an infusion commencing at 0.5 microg kg(-1) min(-1) reducing to 0.25 microg kg(-1) min(-1) after craniotomy. Anaesthesia was induced with propofol, and maintained with either a target-controlled infusion of propofol, minimum target 2 microg ml(-1) or sevoflurane, initial concentration 2%(ET). Episodes of mean arterial pressure (MAP) more than 100 mm Hg or less than 60 mm Hg for more than 1 min were defined as hypertensive or hypotensive events, respectively. A surgical assessment of operating conditions and times to spontaneous respiration, extubation, obey commands and eye opening were recorded. Drug acquisition costs were calculated. RESULTS Twenty-four and twenty-six patients were assigned to propofol (Group P) and sevoflurane anaesthesia (Group S), respectively. The number of hypertensive events was comparable, whilst more hypotensive events were observed in Group S than in Group P (P=0.053, chi-squared test). As rescue therapy, more labetolol [45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21) vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between group differences in recovery times were small and clinically unimportant. The combined hourly acquisition costs of hypnotic, analgesic, and vasoactive drugs appeared to be lower in patients maintained with sevoflurane than with propofol. CONCLUSION Propofol/remifentanil and sevoflurane/remifentanil both provided satisfactory anaesthesia for intracranial surgery.
Endovascular therapy for asymptomatic unruptured intracranial aneurysms: JR-NET and JR-NET2 findings.

BACKGROUND AND PURPOSE National registration studies (the Japanese Registry of Neuroendovascular Therapy [JR-NET] and JR-NET2) have determined the current status and outcomes of neuroendovascular therapy (neuro-EVT). We analyzed short-term outcomes of EVT for asymptomatic unruptured intracranial aneurysms (UIAs). METHODS We extracted periprocedural information about EVT for 4767 asymptomatic UIAs from 31,968 registered procedural records of all EVT in the JR-NET and JR-NET2 databases. We assessed the features of the aneurysms and procedures, immediate radiographic findings, procedure-related complications, and clinical outcomes at 30 days after the procedures. RESULTS We located 80.0% of UIAs in the anterior circulation, and the most frequent were paraclinoid. The diameter of 2.5%, 32.9%, 51.9%, 12.0%, and 0.7% of the UIAs was <3, 3 to 4, 5 to 9, 10 to 19, and >20 mm, respectively. EVT failed in only 2.1%. Adjunctive techniques were applied in 54.8% of procedures. Pre- and postprocedural antiplatelet agents were prescribed in 85.6% and 84.0%, respectively, of the procedures. The immediate radiographic outcomes of 57.7%, 31.9%, and 10.0% of the UIAs comprised complete occlusion, residual necks, and residual aneurysms, respectively. Complications that were associated with 9.1% of procedures comprised 2.0% hemorrhagic and 4.6% ischemic, and the 30-day morbidity and mortality rates were 2.12% and 0.31%, respectively. CONCLUSIONS The radiographic results of EVT for asymptomatic UIAs in Japan were acceptable, with low mortality and morbidity rates.
Pulse wave velocity and ankle brachial index in patients with Kawasaki disease

Abstract Background : Pulse wave velocity (PWV) and ankle brachial index (ABI) are a useful method to estimate atherosclerosis in adults, while a history of Kawasaki disease (KD) may be a risk factor for later atherosclerosis of systemic arteries. PWV and ABI in patients with a history of KD have not been reported.
OFF midget bipolar cells in the retina of the marmoset, Callithrix jacchus, express AMPA receptors

Recent studies suggested that different types of OFF bipolar cells express specific types of ionotropic (AMPA or kainate) glutamate receptors (GluRs) at their contacts with cone pedicles. However, the question of which GluR type is expressed by which type of OFF bipolar cell in primate retina is still open. In this study, the expression of AMPA and kainate receptor subunits at the dendritic tips of flat (OFF) midget bipolar (FMB) cells was analyzed in the retina of the common marmoset, Callithrix jacchus. We used preembedding electron microscopy and double immunofluorescence with subunit‐specific antibodies. The FMB cells were labeled with antibodies against the carbohydrate epitope CD15. Cone pedicles were identified with peanut agglutinin. Immunoreactivity for the GluR1 subunit and for CD15 is preferentially located at triad‐associated flat contacts. Furthermore, the large majority of GluR1 immunoreactive puncta is localized at the dendritic tips of FMB cells. These results suggest that FMB cells express the AMPA receptor subunit GluR1. In contrast, the kainate receptor subunit GluR5 is not colocalized with the dendritic tips of FMB cells or with the GluR1 subunit. Immunoreactive puncta for the GluR1 subunit are found at all M/L‐cone pedicles but are only rarely associated with S‐cone pedicles. This is consistent with our recent findings in marmoset retina that FMB cells do not contact S‐cone pedicles. The presence of GluR5 clusters at S‐cone pedicles indicates that in primate retinas OFF bipolar cells expressing kainate receptor subunits receive some S‐cone input. J. Comp. Neurol. 502:442–454, 2007. © 2007 Wiley‐Liss, Inc.
Transmembrane Topology of Pmt1p, a Member of an Evolutionarily Conserved Family of Protein O-Mannosyltransferases*

The identification of the evolutionarily conserved family of dolichyl-phosphate-d-mannose:proteinO- mannosyltransferases (Pmts) revealed that protein O-mannosylation plays an essential role in a number of physiologically important processes. Strikingly, all members of the Pmt protein family share almost identical hydropathy profiles; a central hydrophilic domain is flanked by amino- and carboxyl-terminal sequences containing several putative transmembrane helices. This pattern is of particular interest because it diverges from structural models of all glycosyltransferases characterized so far. Here, we examine the transmembrane topology of Pmt1p, an integral membrane protein of the endoplasmic reticulum, fromSaccharomyces cerevisiae. Structural predictions were directly tested by site-directed mutagenesis of endogenousN-glycosylation sites, by fusing a topology-sensitive monitor protein domain to carboxyl-terminal truncated versions of the Pmt1 protein and, in addition, by N-glycosylation scanning. Based on our results we propose a seven-transmembrane helical model for the yeast Pmt1p mannosyltransferase. The Pmt1p amino terminus faces the cytoplasm, whereas the carboxyl terminus faces the lumen of the endoplasmic reticulum. A large hydrophilic segment that is oriented toward the lumen of the endoplasmic reticulum is flanked by five amino-terminal and two carboxyl-terminal membrane spanning domains. We could demonstrate that this central loop is essential for the function of Pmt1p.
Membrane‐permeable Bcl‐xL prevents MPTP‐induced dopaminergic neuronal loss in the substantia nigra

The anti‐apoptotic Bcl‐xL is a promising agent to prevent neurodegeneration in Parkinson’s disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl‐xL to a peptide that allows its delivery across biological membranes and the blood–brain barrier. We tested the fusion protein in two models of Parkinson’s Disease. Cell‐permeable Bcl‐xL protected neuroblastoma cells from the selective neurotoxin 1‐methyl‐4‐phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase‐immunoreactive neurons in the substantia nigra pars compacta. Hence, we present that a cell‐permeable form of an anti‐apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases.