Nasopharyngeal airway and subcranial space analysis in Pfeiffer syndrome.

Tracheotomy in infancy helps patients with Pfeiffer syndrome to survive by preventing respiratory crisis, but difficulty in decannulation may consequently be a challenge. This study has investigated the regional abnormalities of the nasopharyngeal airway in children with Pfeiffer syndrome to provide an anatomical basis for the surgical treatment and decannulation of the upper airway. Seventy-two preoperative computed tomograms (CT) (Pfeiffer syndrome n=30; control n=42) were included. The airway volume, cross-sectional area, and cephalometrics were measured using Materialise software. Patients with Pfeiffer syndrome developed a 50% (p<0.001) reduction of nasal airway volume, and a 44% (p=0.003) restriction in pharyngeal airway volume. In patients with Pfeiffer syndrome the cross-sectional area at the choana was only half that of the controls (p<0.001). The posterior width of the nasal airway in patients with Pfeiffer syndrome was shortened by 13% (p=0.003), and the height reduced by 21% (p<0.001). The cross-sectional areas at the condylion and gonion levels, which indicate the calibre of the pharyngeal airway at the entrance and midsection, were reduced by 67% (p<0.001) and 47% (p<0.001), respectively, when compared with the controls. The volume of the nasal airway in patients with Pfeiffer syndrome was significantly restricted in length, height, and width, and by choanal stenosis in all cases in this cohort. The reduced anteroposterior length of the nasal airway contributed to the shortened maxilla more than the anteroposterior position. The limited height and width of the nasal pathway was the result of a hypoplastic sphenoid. Restricted mediolateral and anteroposterior dimensions were evident across the entire course of the pharyngeal airway. Mediolateral maxillary expansion in addition to maxillomandibular advancement is therefore likely to benefit these patients.

Distinguishing craniomorphometric characteristics and severity in metopic synostosis patients.

The decision about which metopic synostosis patients should undergo surgery remains controversial. Multiple measures for radiographic severity have been developed in order to determine the optimal criteria for treatment. The aim of this study was to perform an extensive craniomorphometric analysis of patients who underwent surgery for metopic synostosis to validate and compare the various severity scales developed for this non-syndromic craniosynostosis. A comparative morphometric analysis was performed using computed tomography scans of preoperative metopic synostosis patients (n=167) and normal controls (n=44). Measurements included previous and newly developed metopic severity indices. Volumetric and area analyses were used to determine the degree of anterior cranial area and potential volume restrictions. Of the severity indices measured, the frontal angle, endocranial bifrontal angle (EBF), adjusted EBF (aEBF), anterior cranial fossa angle, horizontal cone angle, and bitemporal/biparietal distance ratio were significantly different in the metopic subjects relative to controls overall. However, metopic index, orbital rim angle, foramen ovale distance, and cranial volume exhibited no significant difference from controls. Only the frontal angle and aEBF correlated with the changes in anterior cranial dimensions observed in metopic synostosis. In conclusion, the frontal angle and aEBF provide the most accurate measures of severity in metopic synostosis.

Growth patterns of the airway in Crouzon syndrome patients with different types of cranial vault suture synostosis.

The severity of obstructive respiratory difficulty varies among affected Crouzon syndrome patients. The aim of this study was to investigate the correlation between the restricted airway volume in Crouzon syndrome and the associated type of cranial vault suture synostosis. Computed tomography scans of 68 unoperated Crouzon syndrome patients and 89 control subjects were subgrouped into four types: type I, bilateral coronal synostosis; type II, sagittal synostosis; type III, pansynostosis; type IV, perpendicular combinations of synostoses. Measurements were made using Mimics software. Of type I Crouzon patients, 42% had a restricted nasal airway (P=0.002), while the pharyngeal airway volume was not significantly reduced. Type II Crouzon patients grew normal segmental airway volumes. Crouzon patients of type III developed simultaneously reduced nasal and pharyngeal airway volumes in infancy, by 38% (P=0.034) and 51% (P=0.014), respectively. However, the nasal airway achieved a normal volume by 2 years of age without any intervention, while the pharyngeal airway remained significantly reduced up to 6 years of age, by 42% (P=0.013), compared to controls. Type IV Crouzon patients developed a reduced nasal airway volume (32%, P=0.048) and a non-significant restricted pharyngeal airway (18%, P=0.325). Airway compromise in Crouzon syndrome is variable when associated with different craniosynostosis fusion patterns. Type II (sagittal synostosis) Crouzon patients grew a normal nasopharyngeal airway volume. Those with types I (bicoronal synostosis) and IV (perpendicular synostoses) had significantly restricted nasal airways and a tendency towards a reduced pharyngeal volume. Type III (pansynostosis) Crouzon infants had the worst restriction of both airways, although there was some improvement with age.

Tet-mediated imprinting erasure in H19 locus following reprogramming of spermatogonial stem cells to induced pluripotent stem cells.

Selective methylation of CpG islands at imprinting control regions (ICR) determines the monoparental expression of a subset of genes. Currently, it is unclear whether artificial reprogramming induced by the expression of Yamanaka factors disrupts these marks and whether cell type of origin affects the dynamics of reprogramming. In this study, spermatogonial stem cells (SSC) that harbor paternalized imprinting marks, and fibroblasts were reprogrammed to iPSC (SSCiPSC and fiPSC). The SSCiPSC were able to form teratomas and generated chimeras with a higher skin chimerism than those derived from fiPSC. RNA-seq revealed extensive reprogramming at the transcriptional level with 8124 genes differentially expressed between SSC and SSCiPSC and only 490 between SSCiPSC and fiPSC. Likewise, reprogramming of SSC affected 26 of 41 imprinting gene clusters known in the mouse genome. A closer look at H19 ICR revealed complete erasure in SSCiPSC in contrast to fiPSC. Imprinting erasure in SSCiPSC was maintained even after in vivo differentiation into teratomas. Reprogramming of SSC from Tet1 and Tet2 double knockout mice however lacked demethylation of H19 ICR. These results suggest that imprinting erasure during reprogramming depends on the epigenetic landscape of the precursor cell and is mediated by TETs at the H19 locus.

Alfentanil attenuates phenylephrine-induced contraction in rat aorta.

BACKGROUND AND OBJECTIVES: Alfentanil was reported to relax the rat aorta by direct action on the vascular smooth muscle. The aims of this in vitro study were to examine the effect of alfentanil on phenylephrine-induced contractions in the rat aorta and to determine the cellular mechanism associated with this process. METHODS: Endothelium-denuded aortic rings were suspended in order to record isometric tension. In the rings with or without 10(-6) mol naloxone or 10(-5) mol verapamil, the concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of alfentanil (10(-6), 5 x 10(-5), 10(-4) mol). In the rings exposed to a calcium-free isotonic depolarizing solution, the contractile response induced by the addition of calcium was assessed in the presence or absence of alfentanil (5 x 10(-5), 10(-4) mol). RESULTS: Alfentanil (5 x 10(-5), 10(-4) mol) attenuated (P < 0.05) the phenylephrine-induced contraction in the ring with or without 10(-6) mol naloxone but had no effect on the phenylephrine-induced contraction in the rings pretreated with verapamil. Alfentanil (5 x 10(-5), 10(-4) mol) produced a significant rightward shift (P < 0.01) in the potassium chloride dose-response curve, and attenuated the contractile response (P < 0.001) induced by calcium in the calcium-free isotonic depolarizing solution in a dose-dependent manner. CONCLUSIONS: A supraclinical dose of alfentanil attenuates the phenylephrine-induced contraction via an inhibitory effect on calcium influx by blocking the l-type calcium channels in the rat aortic vascular smooth muscle.

The fibrinogen degradation products (FgDP) levels in liver disease.

We measured plasma levels of fibrinogen degradation products (FgDP) with newly developed enzyme-linked immunosorbent assay based on monoclonal antibody to assess the fibrinogenolytic state in 52 patients with various liver diseases (27 patients with liver cirrhosis, 10 with chronic hepatitis, 7 with acute hepatitis, 6 with hepatocellular carcinoma, 2 with intrahepatic cholestasis). As compared with 20 healthy subjects (upper limit: 580 ng/ml), elevated plasma levels (660-32000 ng/ml) of FgDP were found in 19 (36.5%) patients. When analyzed according to the underlying disease categories, the magnitude of elevations of FgDP were most prominent in patients with chronic hepatitis. No correlation was found between plasma FgDP levels and serum AST or ALT activity. These findings indicate that increased primary fibrinogenolysis is not rare in liver disease, but poorly correlates with liver function.

Developmental changes of selected minerals in Zucker rats.

Effects of obesity and age on copper, iron, zinc, sodium, potassium, and protein were compared in liver, kidney, brain, and muscle of obese (fa/fa) and nonobese (non-fa/fa) male Zucker rats. Blood plasma cerulopasmin, copper, zinc, sodium, and potassium were also determined. Mean brain weight of fa/fa rats was less than that of non-fa/fa rats at 12 weeks of age; mean brain protein concentration was greater in fa/fa than in non-fa/fa at 5 and 12 weeks of age. At 18-19 days of age, mean sodium concentration (mg/g protein) in liver of fa/fa was less than that of non-fa/fa. At 5 weeks of age, mean copper concentration (microgram/g protein) in kidney was greater in fa/fa. Mean total copper, iron, zinc, sodium, and potassium in liver and kidney were greater in fa/fa than in non-fa/fa at 5 weeks because of the larger livers and kidneys of fa/fa. Mean concentrations of copper, zinc, sodium, and potassium per gram of brain protein were slightly (6-10%) less in fa/fa than in non-fa/fa at 5 weeks. By 12 weeks, mean concentrations of copper in liver, kidney, (tibialis) muscle, and blood plasma, ceruloplasmin in blood plasma, zinc in liver and muscle, iron in muscle, and sodium in liver were greater in fa/fa than in non-fa/fa. However, total amount of each mineral in muscle at 12 weeks was less in fa/fa than in non-fa/fa because of the smaller mean muscle weight of fa/fa. Mean concentrations of copper and zinc in brain and of iron in liver and brain were less in fa/fa than in non-fa/fa at 12 weeks. The major age-related changes in fa/fa that were not observed in non-fa/fa were large increases in liver and kidney copper between 5 and 12 weeks of age. It seems that the abnormal mineral metabolism is a consequence of the obesity, but the mechanisms are not identified.

Inactivation of pea leaf chloroplastic and cytoplasmic glucose 6-phosphate dehydrogenases by light and dithiothreitol.

Chloroplastic and cytoplasmic forms of pea (Pisum sativum L.) leaf glucose-6-P dehydrogenase can be separated by gel electrophoresis. Both forms are found in etiolated seedlings. When light-grown plants are illuminated or when crude extracts are treated with dithiothreitol, the chloroplastic and cytoplasmic forms of this enzyme are inactivated. Michaelis-Menten kinetics are obtained for inactivation of the chloroplastic and cytoplasmic glucose-6-P dehydrogenases and for activation of two dehydrogenases involved in photosynthetic carbon metabolism with dithiothreitol. The mechanism for the activation of the two light-activated enzymes appears to be similar to the mechanism for the inactivation of the chloroplastic and cytoplasmic forms of the light-inactivated oxidative pentose phosphate enzyme glucose-6-P dehydrogenase.

Appearance of Three Chloroplast Isoenzymes in Dark-grown Pea Plants and Pea Seeds.

Activity peaks characteristic of the chloroplastic Calvin cycle enzymes triose-phosphate isomerase, ribose 5-phosphate isomerase, and fructose 1,6-diphosphate aldolase are found in isoelectric focusing patterns of dark-grown pea (Pisum sativum) seedlings and seeds. Apparently, in this higher plant these three chloroplastic isoenzymes can be formed in the absence of light and of chloroplast formation.