Colour differences in Caucasian and Oriental women's faces illuminated by white light-emitting diode sources.

OBJECTIVE: To provide an approach to facial contrast, analysing CIELAB colour differences (ΔEab,10∗) and its components in women's faces from two different ethnic groups, illuminated by modern white light-emitting diodes (LEDs) or traditional illuminants recommended by the International Commission on Illumination (CIE). METHODS: We performed spectrophotometric measurements of spectral reflectance factors on forehead and cheek of 87 young healthy women (50 Caucasians and 37 Orientals), plus five commercial red lipsticks. We considered a set of 10 white LED illuminants, representative of technologies currently available on the market, plus eight main illuminants currently recommended by the CIE, representative of conventional incandescent, daylight and fluorescent light sources. Under each of these 18 illuminants, we analysed the magnitude and components of ΔEab,10∗ between Caucasian and Oriental women (considering cheek and forehead), as well as for cheek-forehead and cheek-lipsticks in Caucasian and Oriental women. Colour-inconstancy indices for cheek, forehead and lipsticks were computed, assuming D65 and A as reference illuminants. RESULTS: ΔEab,10∗ between forehead and cheek were quantitatively and qualitatively different in Orientals and Caucasians, but discrepancies with respect to average values for 18 illuminants were small (1.5% and 5.0% for Orientals and Caucasians, respectively). ΔEab,10∗ between Caucasians and Orientals were also quantitatively and qualitatively different both for forehead and cheek, and discrepancies with respect to average values were again small (1.0% and 3.9% for forehead and cheek, respectively). ΔEab,10∗ between lipsticks and cheek were at least two times higher than those between forehead and cheek. Regarding ΔEab,10∗ between lipsticks and cheeks, discrepancies with respect to average values were in the range 1.5-12.3%, although higher values of up to 54.2% were found for a white RGB LED. This white RGB LED provided the highest average colour-inconstancy indices: 17.1 and 11.5 CIELAB units, under reference illuminants D65 and A, respectively. CONCLUSION: Colour contrasts in women's faces under CIE standard illuminants for outdoor and indoor conditions may be strongly altered using specific white LEDs. More research needs to be performed on the impact of spectral power distribution of light sources with high colour rendering indices on visual colour appearance of cosmetic products.

FOXG1 mutations in Japanese patients with the congenital variant of Rett syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by microcephaly, psychomotor regression, seizures and stereotypical hand movements. Recently, deletions and inactivating mutations in FOXG1, encoding a brain-specific transcription factor that is critical for forebrain development, have been found to be associated with the congenital variant of RTT. Here we report the clinical features and molecular characteristics of two cases of the congenital variant of RTT. We conducted mutation screenings of FOXG1 in a cohort of 15 Japanese patients with a clinical diagnosis of atypical RTT but without MECP2 and CDKL5 mutations. Two unrelated female patients had heterozygous mutations (c.256dupC, p.Gln86ProfsX35 and c.689G>A, pArg230His). Both showed neurological symptoms from the neonatal period, including hypotonia, irritability and severe microcephaly. Further, their psychomotor development was severely impaired, as indicated by their inability to sit unaided or acquire speech sounds, and they had a hyperkinetic movement disorder, because both displayed hand stereotypies and jerky movements of the upper limbs. Brain magnetic resonance imaging scans revealed delayed myelination with hypoplasia of the corpus callosum and frontal lobe. These cases confirm the involvement of FOXG1 in the molecular etiology of the congenital variant of RTT and show the characteristic features of FOXG1-related disorder.

Non-invasive measurement of local pulse pressure by pulse wave-based ultrasound manometry (PWUM).

Central blood pressure (CBP) has been established as a relevant indicator of cardiovascular disease. Despite its significance, CBP remains particularly challenging to measure in standard clinical practice. The objective of this study is to introduce pulse wave-based ultrasound manometry (PWUM) as a simple-to-use, non-invasive ultrasound-based method for quantitative measurement of the central pulse pressure. Arterial wall displacements are estimated using radiofrequency ultrasound signals acquired at high frame rates and the pulse pressure waveform is estimated using both the distension waveform and the local pulse wave velocity. The method was tested on the abdominal aorta of 11 healthy subjects (age 35.7 ± 16 y.o.). PWUM pulse pressure measurements were compared to those obtained by radial applanation tonometry using a commercial system. The average intra-subject variability of the pulse pressure amplitude was found to be equal to 4.2 mmHg, demonstrating good reproducibility of the method. Excellent correlation was found between the waveforms obtained by PWUM and those obtained by tonometry in all subjects (0.94 < r < 0.98). A significant bias of 4.7 mmHg was found between PWUM and tonometry. PWUM is a highly translational method that can be easily integrated in clinical ultrasound imaging systems. It provides an estimate of the pulse pressure waveform at the imaged location, and may offer therefore the possibility to estimate the pulse pressure at different arterial sites. Future developments include the validation of the method against invasive estimates on patients, as well as its application to other large arteries.

Administration of an angiotensin-converting enzyme inhibitor improves vascular function and urinary albumin excretion in low-risk essential hypertensive patients receiving anti-hypertensive treatment with calcium channel blockers. Organ-protecting effects independent of anti-hypertensive effect.

Concomitant administration of calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEIs) to hypertensive patients at high risk for cardiovascular disease can prevent cardiovascular disease occurrence, but the effects of this treatment on renal and vascular function in low-risk hypertensive patients are unknown. The current study was an open-label prospective study. Hypertensive patients with no history of cardiovascular disease who had not met their blood pressure (BP) goals with CCB treatment were administered perindopril and followed for 6 months. Both home and office BP were significantly lowered by perindopril administration. The morning/evening (M/E) ratios calculated from home BP were 1.31 and 1.05 for systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. When the patients were divided into two groups based on the presence or absence of an anti-hypertensive response, urinary albumin excretion, and cardio ankle vascular index were significantly reduced by perindopril administration in all the subjects, irrespective of the presence or absence of anti-hypertensive reaction. In low-risk hypertensive patients, perindopril improves renal and vascular function probably via its persistent anti-hypertensive effects and the concomitant effects of CCB.

Mutations of the E1beta subunit gene (PDHB) in four families with pyruvate dehydrogenase deficiency.

Pyruvate dehydrogenase complex (PDC) deficiencies are a major cause of primary lactic acidosis. Most cases result from mutations of the gene for the pyruvate dehydrogenase E1alpha subunit (PDHA1), with fewer cases resulting from mutations in genes for E3, E3-binding protein, E2, and the E1beta subunit (PDHB). We have found four cases of PDHB mutations among 83 analyzed cases of PDC deficiency. In this series, PDHB mutations were found to be about 10% as frequent as PDHA1 mutations. All cases were diagnosed by low PDC activity, with normal E2 and E3 activities. These included a 6.5-year-old male (consanguineous, homozygous R36C); a neonatal female who died soon after birth, (compound heterozygous C306R/D319V), a 26-year-old female (heterozygous I142M/W165S), and a 13month old female (consanguineous, homozygous Y132C) who is a sibling of a previously published case. Their ethnic background is diverse (Caucasian, Arab, and African American descent). All cases had lactic acidosis and developmental delay. Three cases had agenesis of the corpus callosum, seizures, and hypotonia; one died within the first year of life. These clinical findings are similar to those of PDHA1 deficiency, except that ataxia was more frequent in PDHA1 cases and consanguinity was found only in PDHB families. PDC activity in lymphocytes from six parents is normal, who all are heterozygous carriers for the respective mutations. Immunoreactivity of E1beta was markedly reduced in one case and showed a slightly larger form of E1beta in one case. Computer analysis predicts that: R36C affects the interaction of several amino acids resulting in conformational change, C306R affects interaction of the two beta subunits, D319 is in the interface of E1 and E2, I142M affects conformation around a K ion affecting stability of the beta subunit, W165S affects hydrophobic interaction between the beta subunits, and Y132C affects interaction between the beta subunits. All of these residues are conserved in E1beta across species, and Y132 is also conserved in other TPP-requiring enzymes. These observations support the conclusion that these are pathogenic mutations.

Antithrombin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production by monocytes in vitro through inhibition of Egr-1 expression.

BACKGROUND: Antithrombin (AT) improves the outcome of septic patients with intravascular coagulation. However, the mechanisms underlying the therapeutic benefits of AT are not fully understood. Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the development of organ failure and intravascular coagulation in sepsis. AIM: This study aimed to elucidate a molecular mechanism by which AT inhibits TNF-alpha production. METHODS: Human peripheral monocyte was stimulated by lipopolysaccharide (LPS) and TNF-alpha concentration in media was measured. Levels of phosphorylation of extracellular signal-regulated protein kinases (ERK) 1/2 and early growth response factor-1 (Egr-1) were estimated by western blotting or by electrophoretic mobility shift assay. RESULTS: Antithrombin (3 U mL(-1)) inhibited TNF-alpha production by monocytes stimulated with LPS. Conversely, chemically modified AT that lacks affinity for heparin did not. AT inhibited the phosphorylation of ERK 1/2 and decreased the expression of Egr-1 in LPS-stimulated monocytes. However, it did not affect the activation of either nuclear factor-kappaB or activator protein-1. Pretreatment with KT5720, a protein kinase A inhibitor, reversed the inhibitory effect of AT on the LPS-induced phosphorylation of ERK1/2. Although 2 U mL(-1) AT slightly inhibited TNF-alpha production by LPS-stimulated monocytes, it significantly inhibited TNF-alpha production in the presence of a low concentration of beraprost, a stable derivative of prostacyclin. CONCLUSIONS: These observations suggest that AT might inhibit LPS-induced production of TNF-alpha by inhibiting the increase in Egr-1 expression in monocytes via interaction with heparin-like substances expressed on the cell surface.

Impact of valvular thickness on stroke recurrence in medically treated patients with stroke.

BACKGROUND: It remains controversial whether left-sided valvular thickening (VaT) is a risk factor for ischemic stroke. Little is known about the relationship between VaT and the recurrent adverse event rate in medically treated patients with stroke. METHODS: We examined the outcomes of 627 noncardioembolic stroke patients who were double-blindly assigned to either warfarin or aspirin therapy and assessed VaT using transesophageal echocardiography. Endpoints were recurrent ischemic stroke or death from any cause. The Cox proportional hazards model was used to adjust for covariates. RESULTS: VaT was present in 57.3% of the patients (359/627), 34.6% (271/627) involving the aortic valve and 46.4% (291/627) involving the mitral valve. There was no difference in the time to primary endpoints between those with and without VaT of the aortic valve (p = 0.49; hazard ratio, HR: 1.17; 95% CI: 0.74-1.85; 2-year event rates: 18.9 vs. 13.2%) or mitral valve (p = 0.66; HR: 0.91; 95% CI: 0.60-1.38; 2-year event rates: 16.9 vs. 14.7%). Among the patients with VaT, there was no significant difference in the time to primary endpoints between those treated with warfarin and those with aspirin (p = 0.13, HR: 0.65, 95% CI: 0.37-1.14, 2-year event rates: 15.2 vs. 22.7% for the aortic valve; p = 0.22, HR: 0.70, 95% CI: 0.40-1.23, 2-year event rates: 14.2 vs. 19.6% for the mitral valve). CONCLUSIONS: VaT does not appear to increase recurrent adverse event rates in medically treated patients with ischemic stroke, regardless of warfarin or aspirin therapy.

Search for low-mass exoplanets by gravitational microlensing at high magnification.

Observations of the gravitational microlensing event MOA 2003-BLG-32/OGLE 2003-BLG-219 are presented, for which the peak magnification was over 500, the highest yet reported. Continuous observations around the peak enabled a sensitive search for planets orbiting the lens star. No planets were detected. Planets 1.3 times heavier than Earth were excluded from more than 50% of the projected annular region from approximately 2.3 to 3.6 astronomical units surrounding the lens star, Uranus-mass planets were excluded from 0.9 to 8.7 astronomical units, and planets 1.3 times heavier than Saturn were excluded from 0.2 to 60 astronomical units. These are the largest regions of sensitivity yet achieved in searches for extrasolar planets orbiting any star.

Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury.

BACKGROUND AND OBJECTIVE: Activated protein C (APC) is a natural anticoagulant with anti-inflammatory activity. APC inhibits neutrophil activation through inhibition of tumor necrosis factor (TNF)-alpha production. Such anti-inflammatory activity of APC has recently been shown to be critical in the treatment of patients with severe sepsis. We previously demonstrated that activated neutrophils play a crucial role in the development of stress-induced gastric mucosal injury. Thus, inhibition of neutrophil activation by APC should reduce endothelial cell damage, maintain gastric blood flow, and lessen gastric mucosal injury. In the present study, we examined this possibility by using a rat model of water-immersion restraint stress (WIRS)-induced gastric mucosal injury. METHODS AND RESULTS: Gastric mucosal injury was observed 4 h after WIRS, without increases in gastric mucosal levels of either myeloperoxidase activity or TNF-alpha, but with significant increases in plasma levels of TNF-alpha 1 h after WIRS. Intravenous administration of APC (100 micro g kg-1) significantly reduced WIRS-induced gastric mucosal injury by inhibiting decrease in gastric mucosal blood flow. Administration of APC also inhibited both the decrease in gastric tissue levels of 6-keto-prostaglandin F1alpha and the increase in gastric mucosal micorvascular permeability in animals subjected to WIRS. Furthermore, APC inhibited WIRS-induced increases in plasma levels of TNF-alpha. Neither active site-blocked factor Xa, which is a selective inhibitor of thrombin generation, nor active site-blocked APC had any effect on these events. Intraperitoneal administration of anti-rat TNF-alpha antibody produced effects similar to those of APC. CONCLUSIONS: The observations in the present study strongly suggest that APC reduces stress-induced gastric mucosal injury by inhibiting the decrease in gastric mucosal blood flow through attenuation of the activated neutrophil-induced endothelial cell injury via inhibition of TNF-alpha production. In addition, we show that serine protease activity of APC, rather than its anticoagulant activity, is critical for the protective mechanism(s) by which TNF-alpha production could be inhibited.

Male siblings with dyserythropoiesis, microcephaly and intrauterine growth retardation.

Male siblings with intrauterine growth retardation, hydrops, mild liver dysfunction, chronic diarrhoea, failure to thrive and microcephaly are reported. In both patients, the intrauterine growth retardation was detected in the second trimester of pregnancy. Relatively severe early onset neonatal jaundice, microcytosis, anisocytosis and abnormal iron metabolism were also seen. Bone marrow examination in the second sibling showed marked ringed sideroblasts and multilobulated erythroblasts in late developmental stages. The brain was very small with enlarged cerebrospinal fluid space, a reduced number of gyri and a thin cortex. The clinical and laboratory findings in these patients appear to be unique.

An infomax-based learning rule that generates cells similar to visual cortical neurons.

A learning rule for a visual neural network is derived according to an information-maximization approach. Each basic module of the assumed neural network consists of two simple units and one complex unit. Each simple unit calculates a linear summation of its input by using its synaptic weights, and the complex unit calculates a squared sum of the outputs of the simple units. The learning algorithm updates the synaptic weights of simple units so that the information obtained from the output of the complex unit is increased. Simulation of the algorithm showed that it generates Gabor-wavelet-like weights similar to those observed in visual cortical neurons (simple cells). It also showed that, after the training, the responses of the complex unit are similar to those reported for a complex cell.

Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide.

BACKGROUND: Excessive production of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is critically involved in endotoxin (ET)-induced hypotension. Tumor necrosis factor-alpha (TNF-alpha) plays an important role in induction of iNOS. Because activated protein C (APC), a physiological anticoagulant, inhibits TNF-alpha production, it might prevent hypotension by inhibiting excessive production of NO. In this study, we examined this possibility using a rat model of septic shock. METHODS AND RESULTS: Intravenous administration of APC prevented both ET-induced hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-). The hypotension was also inhibited when APC was administered 30 minutes after ET administration. APC inhibited the increases in lung levels of iNOS activity by inhibiting expression of iNOS mRNA in animals given ET. APC significantly inhibited the increases in lung tissue levels of TNF-alpha and expression of TNF-alpha mRNA in animals given ET. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor DIP-APC, an active site-blocked APC, showed any effect on these ET-induced changes. Both inhibition of TNF-alpha production by leukocytopenia and treatment with anti-rat TNF-alpha antibody produced effects similar to those induced by APC. Aminoguanidine, a selective inhibitor of iNOS, inhibited both the hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-) in this animal model. CONCLUSIONS: These observations strongly suggest that APC inhibits iNOS induction by decreasing TNF-alpha production, leading to the prevention of ET-induced hypotension. Furthermore, such effects of APC were not dependent on its anticoagulant effects but rather on its serine protease activity.

Improvement of the prognosis of gastric cancer with extensive serosal invasion using left upper abdominal evisceration.

BACKGROUND/AIMS: The prognosis of gastric cancer patients with serosal invasion is very poor. In this study, the effectiveness of the LUAE (left upper abdominal evisceration) procedure for these patients was evaluated retrospectively. METHODOLOGY: Thirty-seven gastric cancer patients who had serosal invasion but no massive peritoneal metastasis or hepatic metastasis, and underwent LUAE, were enrolled in this study (LUAE group). As a control, 66 gastric cancer patients who had the same disease conditions as the LUAE group, and underwent conventional total gastrectomy with the combined resection of the pancreatic body and tail and spleen (TPS group), were also investigated. RESULTS: The survival rate (5-year, 42.2%) of the LUAE group was significantly better than that (5-year, 21.2%) of the TPS group (P = 0.009). Although D4 super-extended lymphadenectomy and intraperitoneal chemotherapy during surgery was performed more frequently in the LUAE group than those in the TPS group, multivariate analysis demonstrated that the LUAE procedure was a better independent prognostic factor. CONCLUSIONS: The LUAE procedure in combination with D4 super-extended lymphadenectomy and intraperitoneal chemotherapy improved the prognosis of gastric cancer patients with extensive serosal invasion.

Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3.

A unique type of craniofacial dysostosis, Crouzon syndrome with acanthosis nigricans (CAN), has been attributed to a specific substitution (Ala391Glu) in the fibroblast growth factor receptor 3 (FGFR3) gene. At birth, individuals with this disorder have craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hydrocephalus, and they experience the onset of acanthosis nigricans during childhood. We report three cases and compare the clinical characteristics of our cases with the previously reported cases of this disorder. Since the Ala391Glu substitution in FGFR3 is close to the substitutions in the transmembrane domain that result in achondroplasia, we carefully reviewed the skeletal findings in six patients. We identified subtle radiographic findings of achondroplasia in all six cases including narrow sacrosciatic notches, short vertebral bodies, lack of the normal increase in interpediculate distance from the upper lumbar vertebrae caudally, and broad, short metacarpals and phalanges. Even before acanthosis nigricans appears, the presence of choanal atresia and hydrocephalus in an individual with features of Crouzon syndrome should suggest the diagnosis of CAN, and subtle skeletal findings can lend further support to this diagnosis.

[Molecular markers for the blood coagulation and fibrinolysis].

It is now possible to more precisely evaluate coagulation and fibrinolysis by laboratory tests in which various molecular markers can be measured. The determination of the plasma level of soluble fibrin may be the most important molecular marker for the diagnosis of thrombosis and disseminated intravascular coagulation. Combined with the results of the other molecular marker determinations, the measurement of the plasma level of soluble fibrin might provide useful information about the coagulation status of patients.