Comprehensive histological investigation of age-related changes in dermal extracellular matrix and muscle fibers in the upper lip vermilion.

OBJECTIVE: Few histological studies have directly examined age-related changes within the lips, although non-invasive investigations of such changes are increasing. Therefore, this study aimed to provide histological and molecular data on age-dependent alterations in the vermilion. METHODS: Upper vermilion specimens from 15 female Caucasian cadavers (age range, 27-78 years) were investigated histologically or immunohistochemically. RESULTS: Histologically, age-dependent decreases in areas occupied by hyaluronan and collagenous fibres in the dermis of upper vermilion were demonstrated. Elastic fibre content varied widely between individuals. The area occupied by muscle fibres in the orbicularis oris muscle region within the vermilion also correlated negatively with age. Immunohistochemically, signals of four proteins were attenuated in vermilion from older individuals compared with young individuals: procollagen type I, hyaluronan synthase (HAS)1, myosin heavy chain (MYH)2 (a component of fast-twitch oxidative muscle fibres) and MYH7 (a component of slow-twitch muscle fibres). In contrast, signals of cell migration inducing hyaluronidase 1 (CEMIP) were intensified in vermilion from older individuals. No marked differences between young and older individuals were seen in procollagen type III, HAS2, HAS3, hyaluronidase (HYAL)1, HYAL2, MYH1 or MYH4. CONCLUSION: Age-dependent decreases of hyaluronan in the dermis of vermilion were prominent, possibly due to both the decrease in synthesis (HAS1) and the increase in degradation (CEMIP). Furthermore, age-dependent decreases in collagenous fibres and two types of muscle fibre in the vermilion were also identified histologically. Type I collagen, MYH2 and MYH7 appear to represent the molecules responsible for these respective decrements.

OBJECTIF: Peu d'études histologiques ont examiné directement les changements liés à l'âge sur les lèvres, bien que les enquêtes non invasives de ces changements soient en augmentation. Par conséquent, cette étude visait à fournir des données histologiques et moléculaires sur les altérations liées à l'âge dans le vermillon. MÉTHODES: Des échantillons de vermillon supérieur provenant de 15 cadavres de femme Caucasiens (tranche d'âge, 27-78 ans) ont été étudiés histologiquement ou immuno-histochimiquement. RÉSULTATS: Histologiquement, des diminutions dépendant de l'âge dans les zones occupées par l'hyaluronane et les fibres de collagène dans le derme du vermillon supérieur ont été démontrées. La teneur en fibres élastiques variait considérablement entre les individus. La zone occupée par les fibres musculaires dans la région du muscle orbiculaire oris au sein du vermillon était également corrélée négativement avec l'âge. Immuno-histochimiquement, les signaux de quatre protéines ont été atténués dans vermillon des individus plus âgés que les jeunes: le procollagène type I, l'hyaluronane synthase (HAS) 1, la chaîne lourde de la myosine (MYH) 2 (un composant des fibres musculaires oxydatives à contraction rapide) et MYH7 (un composant des fibres musculaires à contraction lente). En revanche, les signaux du "cell migration inducing hyaluronidase 1 (CEMIP)" ont été intensifiés dans le vermillon des individus plus âgés. Aucune différence marquée entre les individus jeunes et âgés n'a été observée dans le procollagène type III, HAS2, HAS3, hyaluronidase (HYAL) 1, HYAL2, MYH1 et MYH4. CONCLUSION: Les diminutions dépendantes de l'âge du hyaluronane dans le derme du vermillon étaient importantes, probablement en raison à la fois de la diminution de la synthèse (HAS1) et de l'augmentation de la dégradation (CEMIP). En outre, les diminutions dépendantes de l'âge des fibres de collagène et de deux les types de fibres musculaires dans le vermillon ont également été identifiés histologiquement. Le collagène de type I, MYH2 et MYH7 semblent respectivement représenter les molécules responsables de ces diminutions.

Prognostic role of the length of tumour-vein contact at the portal-superior mesenteric vein in patients having surgery for pancreatic cancer.

BACKGROUND: The length of tumour-vein contact between the portal-superior mesenteric vein (PV/SMV) and pancreatic head cancer, and its relationship to prognosis in patients undergoing pancreatic surgery, remains controversial. METHODS: Patients diagnosed with pancreatic head cancer who were eligible for pancreatoduodenectomy between October 2002 and December 2016 were analysed. The PV/SMV contact was assessed retrospectively on CT. Using the minimum P value approach based on overall survival after surgery, the optimal cut-off value for tumour-vein contact length was identified. RESULTS: Among 491 patients included, 462 underwent pancreatoduodenectomy for pancreatic head cancer. PV/SMV contact with the tumour was detected on preoperative CT in 248 patients (53·7 per cent). Overall survival of patients with PV/SMV contact exceeding 20 mm was significantly worse than that of patients with a contact length of 20 mm or less (median survival time (MST) 23·3 versus 39·3 months; P = 0·012). Multivariable analysis identified PV/SMV contact longer than 20 mm as an independent predictor of poor survival, whereas PV/SMV contact greater than 180° was not a predictive factor. Among patients with a PV/SMV contact length exceeding 20 mm on pretreatment CT, those receiving neoadjuvant therapy had significantly better overall survival than patients who had upfront surgery (MST not reached versus 21·6 months; P = 0·002). CONCLUSION: The length of PV/SMV contact predicts survival, and may be used to suggest a role for neoadjuvant therapy to improve prognosis.

ANTECEDENTES: El valor pronóstico de la longitud del contacto del tumor de la cabeza pancreática con las venas porta y mesentérica superior (portal-superior mesenteric vein, PV/SMV) en los pacientes sometidos a cirugía pancreática sigue siendo un tema controvertido. MÉTODOS: Se analizaron los pacientes diagnosticados de un cáncer de la cabeza pancreática a los que se realizó una duodenopancreatectomía cefálica entre octubre de 2002 y diciembre de 2016. El contacto tumoral con la PV/SMV se evaluó de forma retrospectiva mediante tomografía computarizada (TC). Se identificó el valor de corte óptimo para la longitud del contacto tumoral con la PV/SMV, utilizando el valor mínimo de la P basado en la supervivencia global (overall survival, OS) después de la cirugía. RESULTADOS: De 491 pacientes incluidos, en 462 pacientes se realizó una duodenopancreatectomía cefálica por cáncer de la cabeza de páncreas. En la TC preoperatoria, se detectó contacto tumoral con la PV/SMV en 248 (53,7%) pacientes. La OS de los pacientes en los que el contacto del tumor con la PV/SMV fue > 20 mm fue significativamente peor que en aquellos cuyo contacto fue ≤ 20 mm (mediana de supervivencia (median survival time, MST) 23,3 versus 39,3 meses; P = 0,012). En un análisis multivariado se identificó el contacto tumoral-PV/SMV > 20 mm como un factor independiente predictor de mala supervivencia, pero el contacto tumor-PV/SMV > 180° no fue un factor pronóstico. En los pacientes en los que el contacto tumor-PV/SMV fue > 20 mm en el TC preoperatorio, la OS en aquellos que recibieron tratamiento neoadyuvante fue significativamente mejor en comparación con los pacientes tratados directamente con cirugía (MST, no alcanzada versus 21,6 meses, P = 0,002). Conclusión La longitud del contacto tumoral con la PV/SMV predice la supervivencia, por lo cual dicha longitud podría jugar un papel en la indicación de tratamiento neoadyuvante para mejorar el pronóstico.

Inhibition of gingipains and Porphyromonas gingivalis growth and biofilm formation by prenyl flavonoids.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is considered a major pathogen of chronic periodontitis, which also may be implicated with systemic diseases such as atherosclerosis. Secreted cysteine proteases, gingipains Rgp and Kgp, are essential for P. gingivalis virulence. Some polyphenols and flavonoids are known to inhibit gingipain activity and interfere with biofilm formation by P. gingivalis. Many bioactive compounds have been isolated from Epimedium species, but availability of these compounds on gingipains and P. gingivalis is still unclear. Therefore, the aim of this study was to evaluate natural products from medical plants to develop a new therapeutic agent against periodontal disease. MATERIAL AND METHODS: Prenylated flavonoids were isolated from Epimedium species plant using column chromatographies. The inhibitory effect of the prenylated flavonoids against protease activity of gingipains were examined using purified gingipains and fluorogenic substrates. Anti-P. gingivalis activity was evaluated to analyze planktonic growth and biofilm formation in brain heart infusion medium in the presence of the prenylated flavonoids. RESULTS: We isolated 17 prenylated flavonoids (Limonianin, Epimedokoreanin B, etc.) from Epimedium species. We found that some prenylated flavonoids inhibited gingipain activity in a non-competitive manner with Ki values at µm order. The prenylated flavonoids also hindered growth and biofilm formation of P. gingivalis, in a manner independent of gingipain inhibition by the compounds. CONCLUSION: The results indicated an inhibitory effect of the prenylated flavonoids against P. gingivalis and would provide useful information for future development of periodontitis treatment that suppresses gingipains, P. gingivalis growth and biofilm formation.

Marked lateral deviation of the phrenic nerve due to variant origin and course of the thyrocervical trunk: a cadaveric study.

Phrenic nerve impairment can often lead to serious respiratory disorders under various pathological conditions. During routine dissection of an 88-year-old Japanese male cadaver, a victim of heart failure, we recognized an extremely rare variation of the right thyrocervical trunk arising from the subclavian artery laterally to the anterior scalene muscle. In addition to that, the ipsilateral phrenic nerve was drawn and displaced remarkably laterad by this vessel. We examined all of the branches arising from subclavian arteries, phrenic nerves and diaphragm muscles. The embryological background of this arterial variation is considered. The marked displacement with prolonged strain had a potential to cause phrenic nerve impairment with an atrophic change of the diaphragm muscle. Recently many image diagnostic technologies have been developed and are often used. However, it is still possible that rare variations like this case may be overlooked and can only be recognized by intimate regional examination while keeping these rare variations in mind.

Dysgammaglobulinemia Associated With Glu349del, a Hypomorphic XIAP Mutation.

BACKGROUND: X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common. OBJECTIVE: We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene. PATIENTS AND METHODS: We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations. RESULTS: Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP. CONCLUSIONS: Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.

A case of steroid-resistant nephrotic syndrome associated with systemic lupus erythematosus.

We report on an 11-year-old girl who developed steroid-resistant nephrotic syndrome (NS) at the onset of systemic lupus erythematosus (SLE), and clinical and renal histological findings suggested that her NS would be associated with SLE-related podocytopathy. Although initial treatment with intravenous pulse methylprednisolone was ineffective, following treatment with cyclosporine and an angiotensin receptor blocker was effective for her nephrotic proteinuria. She had developed posterior reversible encephalopathy syndrome (PRES), and mycophenolate mofetil (MMF) was started instead of cyclosporine. At present, 45 months after the onset, she is in remission of both NS and SLE. This case indicates that NS associated with SLE-related podocytopathy should be included in the spectrum of glomerulopathy accompanying SLE, also in the pediatric population.

The structure of Venus' middle atmosphere and ionosphere.

The atmosphere and ionosphere of Venus have been studied in the past by spacecraft with remote sensing or in situ techniques. These early missions, however, have left us with questions about, for example, the atmospheric structure in the transition region from the upper troposphere to the lower mesosphere (50-90 km) and the remarkably variable structure of the ionosphere. Observations become increasingly difficult within and below the global cloud deck (<50 km altitude), where strong absorption greatly limits the available investigative spectrum to a few infrared windows and the radio range. Here we report radio-sounding results from the first Venus Express Radio Science (VeRa) occultation season. We determine the fine structure in temperatures at upper cloud-deck altitudes, detect a distinct day-night temperature difference in the southern middle atmosphere, and track day-to-day changes in Venus' ionosphere.

Accurate and rapid novel genetic diagnosis for detection of sentinel lymph node metastasis in breast cancer patients.

BACKGROUND: The transcription-reverse transcription concerted reaction (TRC) test is a novel molecular-based procedure, which can assess nodal metastasis accurately and quickly. We examined the usefulness of the TRC test with a double marker, cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA, to detect sentinel lymph nodes (SLN) metastasis in breast cancer patients. METHODS: A total of 264 SLNs from 131 breast cancer patients were assigned to a training set (109 SLNs from 50 patients) and validation set (155 SLNs from 81 patients). Cytokeratin 19 and CEA mRNA were detected by TRC tests, and the sensitivity and specificity of the SLN metastasis between the TRC and histology cohorts were compared. RESULTS: Mean copy numbers of CK19 and CEA by TRC tests were increased according to the metastatic size. In the training set, TRC test showed 100% sensitivity, specificity and concordance rates against the permanent histopathology test. In the validation set, sensitivity was 97.1%, specificity was 99.2% and the concordance rate was 99.4%. CONCLUSION: Our results showed that the detection of CK19 and CEA mRNA using the TRC test is, an accurate and rapid method for detection of SLN metastasis and can be applied as an intraoperative molecular diagnosis in breast cancer patients.

Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival.

BACKGROUND: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer. METHODS: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases. RESULTS: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356). CONCLUSION: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.

Increased sensitivity to the stimulant effects of morphine conferred by anti-adhesive glycoprotein SPARC in amygdala.

Repeated administration of morphine substantially increases its locomotor-enhancing activity, a phenomenon termed locomotor sensitization. Here we show that secreted protein acidic and rich in cysteine (SPARC), an anti-adhesive glycoprotein present in the basolateral amygdala, contributes to the establishment of locomotor sensitization. The morphine-induced increase in SPARC levels in the basolateral amygdala persisted after morphine withdrawal and coincided with the duration of locomotor sensitization. Moreover, a single injection of morphine after SPARC infusion into the basolateral amygdala of previously uninjected mice substantially enhanced locomotor activity. Thus, SPARC may be an important element for establishing locomotor sensitization to morphine.

Construction of syndromic surveillance using a web-based daily questionnaire for health and its application at the G8 Hokkaido Toyako Summit meeting.

We constructed a syndromic surveillance system to collect directly information on daily health conditions directly from local residents via the internet [web-based daily questionnaire for health surveillance system (WDQH SS)]. This paper considers the feasibility of the WDQH SS and its ability to detect epidemics. A verification study revealed that our system was an effective surveillance system. We then applied an improved WDQH SS as a measure against public health concerns at the G8 Hokkaido Toyako Summit meeting in 2008. While in operation at the Summit, our system reported a fever alert that was consistent with a herpangina epidemic. The highly mobile WDQH SS described in this study has three main advantages: the earlier detection of epidemics, compared to other surveillance systems; the ability to collect data even on weekends and holidays; and a rapid system set-up that can be completed within 3 days.

Brightness modulations of our nearest terrestrial planet Venus reveal atmospheric super-rotation rather than surface features.

Terrestrial exoplanets orbiting within or near their host stars' habitable zone are potentially apt for life. It has been proposed that time-series measurements of reflected starlight from such planets will reveal their rotational period, main surface features and some atmospheric information. From imagery obtained with the Akatsuki spacecraft, here we show that Venus' brightness at 283, 365, and 2020 nm is modulated by one or both of two periods of 3.7 and 4.6 days, and typical amplitudes  <10% but occasional events of 20-40%. The modulations are unrelated to the solid-body rotation; they are caused by planetary-scale waves superimposed on the super-rotating winds. Here we propose that two modulation periods whose ratio of large-to-small values is not an integer number imply the existence of an atmosphere if detected at an exoplanet, but it remains ambiguous whether the atmosphere is optically thin or thick, as for Earth or Venus respectively. Multi-wavelength and long temporal baseline observations may be required to decide between these scenarios. Ultimately, Venus represents a false positive for interpretations of brightness modulations of terrestrial exoplanets in terms of surface features.

The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling.

Inhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor-beta (TGF-beta) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF-beta and bone morphogenetic proteins (BMPs), whereas Smad6 was less effective in inhibiting TGF-beta signaling. Analyses using deletion mutants and chimeras of Smad6 and Smad7 revealed that the MH2 domains were responsible for the inhibition of both TGF-beta and BMP signaling by I-Smads, but the isolated MH2 domains of Smad6 and Smad7 were less potent than the full-length Smad7 in inhibiting TGF-beta signaling. The N domains of I-Smads determined the subcellular localization of these molecules. Chimeras containing the N domain of Smad7 interacted with the TGF-beta type I receptor (TbetaR-I) more efficiently, and were more potent in repressing TGF-beta signaling, than those containing the N domain of Smad6. The isolated N domain of Smad7 physically interacted with the MH2 domain of Smad7, and enhanced the inhibitory activity of the latter through facilitating interaction with TGF-beta receptors. The N domain of Smad7 thus plays an important role in the specific inhibition of TGF-beta signaling.

Gingipains from Porphyromonas gingivalis synergistically induce the production of proinflammatory cytokines through protease-activated receptors with Toll-like receptor and NOD1/2 ligands in human monocytic cells.

Gingipains (HRgpA, RgpB and Kgp) are cysteine proteinases and virulence factors of Porphyromonas gingivalis, the major causative bacterium of periodontal disease. To study synergistic effects of gingipains and signalling via Toll-like receptors (TLRs) and NOD1/2, we investigated effects of a gingipain on the secretion of proinflammatory cytokines from monocytic THP-1 cells in the presence of pathogen-associated molecular patterns (PAMPs). Gingipains stimulated interleukin (IL)-8's secretion from THP-1 cells, which was completely inhibited by proteinase inhibitors of gingipain and increased in the presence of PAMPs. Synergistic effects of gingipains and PAMPs were also seen in the secretion of IL-6 and MCP-1 and reduced to about 50% the secretion of IL-8 from THP-1 cells treated with siRNA targeting either protease-activated receptor (PAR)-1, -2 or -3. PAR agonist peptides mimicked the synergistic effects of gingipains with PAMPs. These results indicate that gingipains stimulate the secretion of cytokines from monocytic cells through the activation of PARs with synergistic effects by PAMPs. This is the first report of synergism of signalling via PARs, and TLRs or NOD1/2. The host defence system against P. gingivalis may be triggered through the activation of PARs by gingipains and augmented by PAMPs from this pathogen via TLRs or NOD1/2.

Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence.

Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1 alpha) of the HBGF-1 beta precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1 alpha lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.

Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.

Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.

Modulation of the functional binding sites for TGF-beta on the type II receptor leads to suppression of TGF-beta signaling.

Transforming growth factor-beta (TGF-beta) binds to two different types of serine/threonine kinase receptors termed type II (TbetaR-II) and type I (TbetaR-I). TGF-beta is unable to bind to TbetaR-I in the absence of TbetaR-II, and initiates receptor assembly by binding with high affinity to TbetaR-II. Previous structural analysis of the TGF-beta3-TbetaR-II complex has suggested that two charged amino acid residues, D55 and E142 of TbetaR-II, are binding sites of TGF-beta. In the present study, we have shown that mutations of the amino-acid residues, D55 and E142 of TbetaR-II, resulted in loss of TGF-beta binding and downstream signaling activity. Moreover, we found that 3,5,7,2',4'-pentahydroxyflavone (Morin) inhibits TGF-beta binding to TbetaR-II, and suppresses phosphorylation of Smad2 and expression of a TGF-beta target gene Smad7 induced by TGF-beta. Our findings may thus provide useful information for designing therapeutic agents for various diseases induced by TGF-beta, including advanced cancers.

A survey of patients with self-reported severe food allergies in Japan.

Food allergies have increased in recent years in Japan. Details of causative foods, places where anaphylaxis developed, and other allergic factors remain unknown, and we investigated them. A'questionnaire survey for the prevention of food allergies' was conducted using a nationwide group of patients with food allergies. A total of 1383 patients from 878 families (including 319 patients who experienced anaphylaxis) provided valid answers to the questionnaire. The average age of the first anaphylactic attack was 3.20 +/- 6.327 yr. The most common allergens causing anaphylaxis were in order milk, eggs, wheat, peanuts, and soybeans, followed by sesame and buckwheat. The most common place where anaphylaxis developed was the patient's own home, followed by fast food restaurants, places visited, restaurants, and schools. In patients' own homes, fast food restaurants (buffet), places visited and schools, the most common allergens were milk, eggs, and wheat. In restaurants and accommodation facilities, eggs were the most common allergen followed by milk. As possible food allergies can cause anaphylaxis, it is necessary to provide precise information for consumers regarding packaged and processed foods.

Frequent nocturnal vocalization in pure autonomic failure.

Nocturnal vocalization is frequent in Parkinson's disease patients with rapid eye movement (REM) sleep behaviour disorder (RBD). We investigated the frequency of nocturnal vocalization and other sleep problems in patients with pure autonomic failure (PAF) and compared the results with idiopathic Parkinson's disease (IPD) and dementia with Lewy bodies (DLB). We interviewed consecutive patient-caregiver pairs with PAF (n = 13), IPD (n = 200) and DLB (n = 19), and ischaemic stroke patients (controls, n = 43). Nocturnal vocalization was similarly frequent in PAF, IPD and DLB. Other dream enactments and vivid dreams also were more frequent in PAF, IPD and DLB compared with controls. Excessive night-time awakenings and daytime sleepiness were frequent in IPD but rare in PAF and controls. Clinical manifestation of sleep disturbances, at least of RBD-like symptoms including nocturnal vocalization and other dream enactments, may occur in PAF, as in IPD and DLB.