Effects of the histone deacetylase inhibitor ITF2357 in autoinflammatory syndromes

We explored the effects of the oral histone deacetylase (HDAC) inhibitor ITF2357 in patients with autoinflammatory syndrome. In this prospective open-label pilot study, eight patients were enrolled; one patient with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), three patients with hyper-IgD and periodic fever syndrome (HIDS) and four patients with Schnitzler syndrome were closely followed during 90 d of ITF2357 treatment. Three patients with Schnitzler syndrome and one TRAPS patient experienced a partial remission. In four patients, there was no effect. In HIDS patients, there was a tendency toward a higher attack frequency and increasing attack severity. In two patients (one TRAPS and one HIDS), we observed a decrease of acute-phase response without signs of clinical improvement. One patient with Schnitzler syndrome showed a partial response despite an ongoing acute-phase response. In conclusion, ITF2357 monotherapy was able to induce partial response only in patients with Schnitzler syndrome and no response in patients with HIDS.     

Genetic dissection of the syndrome X in the rat

In 1988, Reaven used the term syndrome X to describe a relation between several disorders including hypertension, dyslipidemia, impaired glucose tolerance, obesity, and coronary heart disease. Despite a number of studies dealing with syndrome X, its genetic basis remains poorly understood. Regarding the complexity of this syndrome, it is important to use animal models developing the traits of the disease. Here we show a genetic dissection of syndrome X in the WOKW rat, an animal model of genetically determined syndrome X. We found a major quantitative trait locus (QTL) for glucose metabolism on chromosome 3 and further QTLs influencing obesity and body weight on chromosomes 1 and 5. Genetic determinants of dyslipidemia were mapped to chromosomes 4 and 17. In addition, suggestive linkage for serum insulin was found on chromosome 1 to the region previously shown to be associated with type-1 diabetes mellitus. This is the first study demonstrating independent genetic factors influencing traits of the syndrome X in the rat as well as a possible genetic relationships between syndrome X and diabetes mellitus. Moreover, regarding the close similarities between WOKW rat and human syndrome X, the study could help in a search of genetic factors involved in this complex metabolic disorder in human.     

Changes in renal haemodynamics in the nephrotic syndrome

It has repeatedly been found that haemodynamic changes during hypoproteinaemia in the chronic phase of the nephrotic syndrome are different from those during hypoproteinaemia in the acute phase. In our series of patients, a decrease in the filtration fraction and relative hyperperfusion of the kidneys were associated with the presence of the nephrotic syndrome. No significant changes in renal haemodynamics were observed in patients with chronic glomerulonephritis without the nephrotic syndrome or in a group of healthy volunteers. The question of whether relative hyperperfusion of the kidneys in a repeatedly relapsing nephrotic syndrome can lead to the development of focal segmental glomerulosclerosis needs to be elucidated.     

High incidence of free monoclonal lambda light chains in the sera of patients with Sjogren's syndrome

Sjogren's syndrome presents a wide spectrum of disease manifestations ranging from benign to malignant lymphoproliferation. Sera from 21 patients with primary Sjogren's syndrome, 63 patients with other autoimmune rheumatic diseases, and 140 normal controls were studied by using high-resolution gel electrophoresis combined with immunofixation and specific absorption studies. Two-thirds of the sera from Sjogren's syndrome patients contained free monoclonal lambda light chains. In addition, one patient with Sjogren's syndrome and pseudolymphoma had a circulating monoclonal IgM-lambda immunoglobulin. In contrast, only 16% of the patients with other autoimmune diseases and 5% of normals had monoclonal bands; none of the other patients studied exhibited monoclonal-free lambda light chains in their serum. Our findings suggest that the monoclonal process in Sjogren's syndrome starts early in the disease process in a subset of B cells.     

Mutagen sensitivity and the repair process of the lymphocytes in the Werner syndrome

In this study, we analyzed the cell cycle kinetics, the radiosensitivity, the repair process and the induction of sister chromatid exchanges in lymphocytes from the Werner's syndrome. When compared to a normal population, no statistical significant differences were observed for the cell cycle kinetics and the radiosensitivity. However, differences exist with respect to the repair process and lymphocytes from the Werner's syndrome are much more sensitive to the induction of SCE's.     

Dynamics of contraction of the left and right ventricles of the heart (according to kinetocardiography data) in the development of renovascular hypertension in dogs of various ages]

Kinetocardiograms of the left and the right ventricles of the heart were recorded in puppies and adult dogs during development in them of experimental renovascular hypertension. Development of hypertension in adult dogs led to the shortening of ejection period, and in puppies--to its prolongation. The vector analysis of kinetocardiograms demonstrated in adult dogs the appearance of the syndrome of hypodynamics of the left ventricle replaced later by the syndrome of high diastolic pressure. In the puppies' left ventricle there appeared the phasic syndrome of high diastolic pressure replaced by the syndrome of stenosis of the exit tract. The phasic structure of the cycle of the right ventricle is characterized by the appearance of the syndrome of hyperdynamia detectable earlier in adult dogs.     

Behavioural Studies in the Veterinary Curriculum

Down syndrome is often used in high school and college biology classes as an example of human cytogenetic anomaly. In this paper we discuss the conventional interpretation of the aetiology of Down syndrome and summarize recent data which do not support the conventional interpretation. Twenty-seven college level texts were reviewed for the way in which they present clinical, cytogenetic, and statistical findings on Down syndrome.     

Glomerular anionic charge in congenital nephrotic syndrome of the Finnish type

Summary Decrease of the anionic charge of the glomerular basement membrane and especially the reduced amount of heparan sulphate proteoglycan in the lamina rara externa has been suggested to be the basic pathogenetic defect in congenital nephrotic syndrome. In the present study the anionic charge of glomeruli was examined in the congenital nephrotic syndrome of the Finnish type and in controls using cationic stains (polyethyleneimine, Ruthenium Red) in electron microscopy. Chondroitinase and heparinase treatments were used to characterize further the anionic elements detected. Scanning electron microscopy (SEM) was used in addition to transmission electron microscopy (TEM) to examine the tridimensional structure and secondary changes of podocytes in this syndrome. The number (mean ± SD) of polyethyleneimine granules per 1 μm length of lamina rara externa of the glomerular basement membrane was 24.9 ± 4.5 in control and 2.32 ± 4.3 in congenital nephrotic syndrome subjects. The Ruthenium Red staining pattern was closely similar in syndrome and control kidneys. The granules evident after staining with either cationic stain were seen after chondroitinase but not after heparinase treatment in control as well as in syndrome patient kidney samples. No denuded areas of basement membrane in 42 glomeruli from four syndrome patients were found in SEM. In conclusion, the amount of anionic sites in the lamina rara externa as detected by either cationic stain was comparable to controls. These results do not support the hypothesis of decreased anionic sites in the lamina rara externa of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type.     

Immunological alteration of the Bloom's syndrome uracil DNA glycosylase in Epstein-Barr virus-transformed human lymphoblastoid cells

The immunological reactivity of the uracil DNA glycosylase was investigated in three Epstein-Barr virus-transformed human lymphoblastoid cell lines. Two were derived from normal human lymphocytes while the third was derived from a Bloom's syndrome patient. A panel of 3 anti-human placental uracil DNA glycosylase monoclonal antibodies (37.04.12, 40.10.09 and 42.08.07) was used. Immunological reactivity was determined in a double-blind enzyme-linked immunosorbent assay (ELISA); by inhibition of enzyme activity; and by immunoblot analysis. In the ELISA, the glycosylase from each lymphoblastoid cell line was recognized by glycosylase antibodies 37.04.12 and 42.08.07. In contrast, antibody 40.10.09 failed to recognize the glycosylase from the Bloom's syndrome cell line. Further analysis demonstrated that the 40.10.09 antibody was unable to inhibit catalysis by the Bloom's syndrome lymphoblast glycosylase. In contrast, the 40.10.09 antibody inhibited the activity of the two normal human lymphoblast enzymes. Denaturation of the Bloom's syndrome lymphoblast glycosylase rendered that protein immunoreactive with the 40.10.09 antibody. These results demonstrated that: (1) the immunological alteration in the Bloom's syndrome uracil DNA glycosylase was detected in hematopoietic cells; and (2) viral transformation did not affect the immunoreactivity of the enzyme from either normal human or Bloom's syndrome cells.     

The Opitz hypertelorism-hypospadias syndrome. Further delineation of the spectrum of clinical findings

In this paper we report three male patients with the Opitz hypertelorism-hypospadias syndrome. In addition to the typical morphological findings, signs of cerebral palsy related to dysmaturity and perinatal adaptation problems were present in two of them. This illustrates that this syndrome is a true multiple congenital anomaly/mental retardation MCA/MR syndrome with great variability in expression of clinical symptoms.     

Cosegregation of elastin-associated microfibrillar abnormalities with the Marfan phenotype in families.

The Marfan syndrome is a serious heritable connective-tissue disorder characterized primarily by ocular, cardiovascular, and musculoskeletal abnormalities but also involving multiple other tissues and organs of the body. Inherited as an autosomal dominant disorder, the etiology and pathogenesis of the Marfan syndrome are presently unknown. We have documented consistent apparent deficient content of elastin-associated microfibrillar fibers by indirect immunofluorescent (IF) studies of Marfan skin, as well as deficient accumulation of related fibrous materials in cultures of Marfan fibroblasts as compared with normal controls and patients with other heritable disorders of connective tissue. These data have suggested that abnormalities in the microfibrillar component of elastic-fiber systems may have a role in the etiology and pathogenesis of the Marfan syndrome. In the present study, we have analyzed the IF staining patterns of skin and fibroblast cultures from Marfan syndrome patients and normal first-degree relatives in nine Marfan kindreds. Three of these families had at least one affected individual in each of 2 generations, permitting intergenerational comparison of IF patterns. Six kindreds had one or more affected individuals in a single generation, making comparisons between siblings and/or parent-child possible. In all cases, IF abnormalities cosegregated with the Marfan phenotype and all nonaffected family members were normal. Within family groups containing more than one affected individual, the IF staining patterns were similar between affected patients. These data provide further confirmation of consistent and relatively specific deficiency of microfibrillar fibers in Marfan syndrome.     

Appearance of microthrombi in vessels of central nervous system in the course of disseminated intravascular coagulation syndrome in acute leukemias

In 35 cases out of 37 (88%) microthrombi have been found in CNS. They appeared much more frequently than it could be expected on the basis of the clinical picture of DIC syndrome or changes in the coagulation system. Microthrombi occurred prevalently in white substance of the frontal and occipital lobes as well as in thalamus. In 15 cases the microthrombi were the only evidence of DIC syndrome, besides clinically "mute" one. It should be emphasized that almost in half of the cases we encountered numerous disseminated microthrombi in many regions of CNS. Unequal distribution of microthrombi in CNS points out the significance of the local factor in the pathogenesis of DIC syndrome.     

Smoking dose modifies the association between C242T polymorphism and prevalence of metabolic syndrome in a Chinese population

Background

The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. Oxidase is a major source of the superoxide anion that contributes to individual components of metabolic syndrome. We examined the relationship of the C242T polymorphism with the prevalence of metabolic syndrome in a Chinese population, taking account of consumed cigarette amounts.

Methodology/Principal Findings

In 870 participants, we collected biomarkers related to metabolic syndrome and detailed history of smoking and genotyped the C242T polymorphisms. After adjustment for covariates, the CT/TT genotypes were associated with a lower risk of metabolic syndrome (P = 0.0008). The odds of having metabolic syndrome in the CT/TT participants were 0.439 (95%CI: 0.265, 0.726), while for CC participants the odds were 1.110 (95%CI: 0.904, 1.362). There was significant (P = 0.014) interaction between the C242T polymorphism and smoking status in relation to the prevalence of metabolic syndrome. For smokers who smoke no less than 25 pack-years, those with CT/TT genotypes had lower risk of metabolic syndrome as compared with CC polymorphism carriers (P = 0.015). In the multiple regression analysis, the CT/TT genotypes were significantly associated with lower serum concentration of triglycerides both in all subjects and smokers; furthermore, the CT/TT genotypes were also related to smaller waist circumference in smokers.

Conclusions

Our study suggests that the C242T gene polymorphism is indeed related to the prevalence of metabolic syndrome and smoking dose might modify this association.     

基于网络药理学探讨“黄芪-白术-熟地黄”组方防治肾病综合征的作用机制

本研究旨在通过网络药理学方法和分子对接技术探讨黄芪-白术-熟地黄组方(HBS)治疗肾病综合征的作用机制.通过多个数据库获取肾病综合征基因并进行功能模块分解,找出肾病综合征基因参与的主要生物学过程.通过文献以及数据库查找HBS活性成分和基因靶点,筛选出HBS治疗肾病综合征的有效靶点.通过有效靶点的KEGG和GO富集分析,...     

Histology of the pharyngeal constrictor muscle in 22q11.2 deletion syndrome and non-syndromic children with velopharyngeal insufficiency

Plastic surgeons aim to correct velopharyngeal insufficiency manifest by hypernasal speech with a velopharyngoplasty. The functional outcome has been reported to be worse in patients with 22q11.2 deletion syndrome than in patients without the syndrome. A possible explanation is the hypotonia that is often present as part of the syndrome. To confirm a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome, specimens of the pharyngeal constrictor muscle were taken from children with and without the syndrome. Histologic properties were compared between the groups. Specimens from the two groups did not differ regarding the presence of increased perimysial or endomysial space, fiber grouping by size or type, internalized nuclei, the percentage type I fibers, or the diameters of type I and type II fibers. In conclusion, a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome could not be confirmed.     

Lung immunoglobulins in the sudden infant death syndrome.

The incidence of the sudden infant death syndrome parallels that of respiratory tract infections in the paediatric community. On the basis that the aetiology of the sudden infant death syndrome may lie in an unusual response to a trivial intercurrent respiratory infection a necropsy study was carried out investigating pulmonary immunoglobulins in 16 victims of the syndrome and a series of infants (controls) who had died of non-pulmonary causes. Compared with the controls victims of the sudden infant death syndrome had grossly raised concentrations of IgG, IgM, and to a less extent IgA in lung lavage samples. In addition, pulmonary interstitial and terminal airway cells expressing these immunoglobulins were identified far more often in victims than controls. The study failed to determine whether the increased immunoglobulin concentrations were a consequence of an unusual response to a trivial infection or an expression of otherwise altered immunological control in the respiratory tract. Epidemiological evidence and the findings of this study suggest that the respiratory tract is the prime target organ in the sudden infant death syndrome.     

Potential role of taurine in the prevention of diabetes and metabolic syndrome

Metabolic syndrome is characterized by the cluster of a number of metabolic abnormalities in the presence of underlying insulin resistance. The prevalence of metabolic syndrome has steadily increased in all populations worldwide. Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid that is involved in a variety of physiological functions. Clinical and experimental studies show that taurine intake may be beneficial in the prevention of metabolic syndrome including diabetes, obesity, dyslipidemia, and hypertension. This article reviews the effect of taurine on all of the components of metabolic syndrome. In addition, the possible mechanisms by which taurine prevents diabetes and metabolic syndrome are also discussed. Further study is needed to determine the role of taurine in the development of metabolic syndrome in humans, because there is presently limited clinical data available.     

Craniofacial manifestations in the Marfan syndrome: palatal dimensions and a comparative cephalometric analysis

The purpose of this study was to determine how the craniofacial morphology, evaluated from dental casts and lateral cephalograms, in individuals affected by the Marfan syndrome diverge from healthy control groups. The high and narrow palatal vault as well as maxillary and mandibular retrognathy were strongly correlated to the syndrome. About 70% of the Marfan syndrome patients (n = 76) had been referred for orthodontic treatment, mostly because of crowded teeth or extreme maxillary overjet. In 36%, the orthodontic treatment was carried out before diagnosis or suspicion about the Marfan syndrome. In comparison to healthy orthodontic patients (n = 86), selected because of presence of high and narrow palatal vaults, crowding of teeth, extreme maxillary overjet, and open bite were much more prevalent in the Marfan syndrome patients than in the orthodontic control group.     

Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom's syndrome gene

The SGS1 of Saccharomyces cerevisiae is a homologue of the Bloom's syndrome and Werner's syndrome genes. The sgs1 disruptants show hyperrecombination, higher sensitivity to methyl methanesulfonate and hydroxyurea, and poor sporulation. In this study, we found that sister chromatid exchange was increased in sgs1 disruptants. We made mutated SGS1 genes coding a protein proved to lack DNA helicase activity (sgs1-hd), having equivalent missense mutations found in Bloom's syndrome patients (sgs1-BS1, sgs1-BS2). None of the mutated genes could suppress the higher sensitivity to methyl methanesulfonate and hydroxyurea and the increased frequency of interchromosomal recombination and sister chromatid exchange of sgs1 disruptants. On the other hand, all of the mutant genes were able to complement the poor sporulation phenotype of sgs1 disruptants, although the values were not as high as that of wild-type SGS1.     

Response to three seasons of elevated ozone in the progeny of healthy and unhealthy Norway spruce trees from a plantation with the 'top dying' syndrome

We tested a hypothesis that elevated ozone was an eliciting or contributing factor in outbreaks of the 'top dying' (or 'subtop dying') syndrome in Norway spruce ( Picea abies ). Progeny were used from open-pollinated trees within a stand with the 'top dying' syndrome. The mother trees were classified in relation to the expression of the 'top dying' syndrome, and progeny from the healthiest and least healthy thirds of the population were exposed to high and low concentrations of ozone for three seasons. Elevated ozone did not affect height growth of the trees. It did not measurably affect net photosynthesis, stomatal conductance or instantaneous water use efficiency. Chlorophyll and carotenoid contents were also not significantly affected by ozone concentration. In the first year, instantaneous water use efficiency was lower in the progeny of the unhealthy mother trees than in the healthy mother trees. Furthermore, the unhealthy mother trees tended to produce longer annual shoots and showed more winter damage at the end of the experiment. None of these parameters were related to ozone concentration in the atmosphere. These results do not support a hypothesis that elevated ozone is a significant contributory factor or an eliciting factor in the development of the syndrome.