MR Imaging Detection of CNS Lesions in Tuberous Sclerosis Complex: The Usefulness of T1WI with Chemical Shift Selective Images.

BACKGROUND AND PURPOSE: CNS lesions of tuberous sclerosis complex are diagnosed mainly by T2WI, FLAIR, and sometimes T1WI with magnetization transfer contrast. The usefulness of T1WI with chemical shift selective images was recently reported in focal cortical dysplasia type IIb, which has histopathologic and imaging features similar to those of tuberous sclerosis complex. We investigated the usefulness of the T1WI with chemical shift selective images in detecting CNS lesions of tuberous sclerosis complex. MATERIALS AND METHODS: We retrospectively reviewed 25 consecutive patients with tuberous sclerosis complex (mean age, 11.9 [SD, 8.9] years; 14 males) who underwent MR imaging including T1WI, T1WI with magnetization transfer contrast, T1WI with chemical shift selective, T2WI, and FLAIR images. Two neuroradiologists assessed the number of CNS lesions in each sequence and compared them in 2 steps: among T1WI, T1WI with magnetization transfer contrast and T1WI with chemical shift selective images, and among T2WI, FLAIR, and T1WI with chemical shift selective images. We calculated the contrast ratio of the cortical tubers and of adjacent normal-appearing gray matter and the contrast ratio of radial migration lines and adjacent normal-appearing white matter in each sequence and compared them. RESULTS: T1WI with chemical shift selective images was significantly superior to T1WI with magnetization transfer contrast for the detection of radial migration lines and contrast ratio of radial migration lines. There was no significant difference between T1WI with chemical shift selective images and T1WI with magnetization transfer contrast for the detection of cortical tubers and the contrast ratio of the cortical tubers. Both T2WI and FLAIR were statistically superior to T1WI with chemical shift selective images for the detection of cortical tubers. T1WI with chemical shift selective images was significantly superior to T2WI and FLAIR for the detection of radial migration lines. CONCLUSIONS: The usefulness of T1WI with chemical shift selective images in detecting radial migration lines was demonstrated. Our findings suggest that the combination of T1WI with chemical shift selective images, T2WI, and FLAIR would be useful to evaluate the CNS lesions of patients with tuberous sclerosis complex in daily clinical practice.

The muscular dystrophic chicken is hypernatremic.

1. The E3 ubiquitin protein ligase 1 (WWP1) gene, the mutation of which causes muscular dystrophy in chickens, is expressed not only in the pectoral muscle, but also in a number of tissues such as the kidney. Therefore, this study examined some parameters related to kidney function in muscular dystrophic (MD) chickens. 2. Plasma osmolality, Na+ and K+ concentrations, aldosterone levels, and the expression of aquaporin (AQP) 2, AQP3, and α subunits of the amiloride-sensitive epithelial sodium channel (αENaC) were analysed in the kidneys of 5-week-old MD chickens and White Leghorn (WL) chickens under physiological conditions or after one day of water deprivation. 3. Plasma osmolality, Na+ concentrations, and plasma aldosterone levels were significantly higher in MD chickens than in WL chickens. αENaC mRNA expression levels were lower in MD chickens than in WL chickens. AQP2 and AQP3 mRNA expression levels were similar in the two strains of chickens. 4. Plasma osmolality correlated with aldosterone levels and AQP2 and αENaC mRNA levels in WL chickens. In MD chickens, plasma osmolality correlated with AQP2 mRNA levels, but not with plasma aldosterone or αENaC mRNA levels. 5. These results suggest that neither water reabsorption nor the expression of AQP2 and AQP3 is impaired in MD chickens and that a WWP1 gene mutation may or may not directly induce an abnormality in Na+-reabsorption in the kidneys of MD chickens, potentially through αENaC.

First signs of late-presenting cervical lymph node metastasis in oral cancers during follow-up.

One of the most important prognostic factors in oral squamous cell carcinoma (OSCC) is the presence of lymph node metastasis. Therefore, the early detection of late-presenting cervical lymph node metastasis is important. Although many studies have assessed diagnostic modalities for detecting metastatic cervical lymph nodes, no study has evaluated the process, especially first signs, for detecting late-presenting cervical lymph node metastasis. A retrospective analysis comparing methods for detecting the first signs of late-presenting lymph node metastasis was performed. A total of 65 OSCC patients were assessed. These patients were identified retrospectively as having presented late metastasis during follow-up after initial treatment with curative intent. The findings of four detection methods were analyzed: palpation, ultrasonography, computed tomography, and subjective symptoms. The numbers of cases identified by each method were as follows: palpation, 31 (47.7%); ultrasonography, 17 (26.1%); computed tomography, 12 (18.5%); and subjective symptoms, 5 (7.7%). Palpation played a major role in the discovery of late-presenting lymph node metastasis. In contrast, metastatic lymph nodes were detected by other methods in about half of the cases. The results suggest a possible stratification of the various methods used for metastatic lymph node detection, depending on the characteristics of individual cases.

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR.

Although allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor (MSD) is a potentially curative post-remission treatment for adults with acute myeloid leukemia (AML) in their first CR, transplant-related morbidity and mortality remains a major drawback. We retrospectively compared the outcomes of patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT; n=375) with those who underwent allogeneic bone marrow transplantation (allo-BMT; n=521) and allo-PBSCT (n=380) from MSDs for adults with AML/CR1, in which propensity score models were used to adjust selection biases among patients, primary physicians and institutions to overcome ambiguity in the patients' background information. Both the multivariate analysis and propensity score models indicated that the leukemia-free survival rate of auto-PBSCT was not significantly different from that of allo-BMT (hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.92 to 1.66; P=0.16) and allo-PBSCT (HR, 1.13; 95% CI, 0.85-1.51; P=0.40). The current results suggest that auto-PBSCT remains a promising alternative treatment for patients with AML/CR1 in the absence of an available MSD.

The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro.

Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical.

Intraocular Ossification in the GSP/pe Chicken With Imperfect Albinism.

The eyes of 2 male and 2 female GSP/pe chickens, the imperfect albino strain, were investigated at 52 weeks of age. Aged chickens of the GSP/pe colony became blind with bilateral ocular enlargement and opaque lenses. Affected eyes (bilateral in 2 males and unilateral in 2 females) were hard and difficult to section; histologic specimens were processed after decalcification. A large portion of the posterior chamber was occupied by cancellous bone containing fibrous and cartilaginous foci. Osseous tissues developed adjacent to the choroid, and no retinal pigment epithelium (RPE) was detected between osseous tissues and the choroid. Small segments of degenerate neuronal retina were scattered in the osseous tissue. The irises and ciliary bodies were deformed by osseous tissue, and the lenses had severe cataracts. These observations suggest that the intraocular osseous tissue may be derived from RPE in the hereditary incomplete-albino strain of chickens.

Cost-effective development of highly polymorphic microsatellite in Japanese quail facilitated by next-generation sequencing.

Next-generation sequencing technologies permit rapid and cost-effective identification of numerous putative microsatellite loci. Here, from the genome sequences of Japanese quail, we developed microsatellite markers containing dinucleotide repeats and employed these for characterisation of genetic diversity and population structure. A total of 385 individuals from 12 experimental and one wild-derived Japanese quail lines were genotyped with newly developed autosomal markers. The maximum number of alleles, expected heterozygosity and polymorphic information content (PIC) per locus were 10, 0.80 and 0.77 respectively. Approximately half of the markers were highly informative (PIC ≥ 0.50). The mean number of alleles per locus and observed heterozygosity within a line were in the range of 1.3-4.1 and 0.11-0.53 respectively. Compared with the wild-derived line, genetic diversity levels were low in the experimental lines. Genetic differentiation (FST ) between all pairs of the lines ranged from 0.13 to 0.83. Genetic clustering analyses based on multilocus genotypes of individuals showed that most individuals formed clearly defined clusters corresponding to the origins of the lines. These results suggest that Japanese quail experimental lines are highly structured. Microsatellite markers developed in this study may be effective for future genetic studies of Japanese quail.

A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer.

PURPOSE: Better treatments for triple-negative breast cancer (TNBC) are needed. To address this need, we studied the effects of preoperative metronomic paclitaxel/cyclophosphamide/capecitabine (mPCX) followed by 5-fluorouracil (FU)/epirubicin/cyclophosphamide (FEC) as preoperative chemotherapy in TNBC patients. METHODS: Forty primary TNBC patients received four cycles of metronomic paclitaxel (80 mg/m(2) on Days 1, 8, and 15), cyclophosphamide (50 mg/body daily), and capecitabine (1,200 mg/m(2) daily), followed by four cycles of 5-FU (500 mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) every 3 weeks. The primary end point was the pathological complete response (pCR) rate. RESULTS: Forty patients formed the intent-to-treat population. The median dose intensities of paclitaxel, cyclophosphamide, and capecitabine were 89.7, 92.1, and 89.8%, respectively. Five patients discontinued mPCX and two discontinued FEC, primarily because of adverse events, resulting in a per-protocol population (PPS) of 33 patients. The pCR (ypT0/Tis ypN0) rate was 47.5% (19/40) in the intent-to-treat population and 54.5% (18/33) in the PPS. The clinical response rates were 36/40 (90.0%) and 31/33 (93.9%) in the intent-to-treat and PPS, respectively. The breast conservation rate was 72.7% (24/33), and 5/13 patients underwent partial resection instead of pre-planned total mastectomy. Grade 3-4 adverse events included neutropenia (35%), leukopenia (25%), and hand-foot syndrome (8%). CONCLUSIONS: Metronomic PCX followed by FEC chemotherapy was associated with a high pCR rate and low toxicity in TNBC patients. Further studies of this regimen in larger numbers of patients are warranted.

Comparison of microsatellite variations between Red Junglefowl and a commercial chicken gene pool.

It is assumed that Red Junglefowl (Gallus gallus) is one of the main ancestors of domestic chickens (Gallus gallus domesticus). Differences in microsatellite polymorphisms between Red Junglefowl and modern commercial chickens, which are used for egg and meat production, have not been fully reported. A total of 361 individuals from 1 Red Junglefowl population that has been maintained as a closed flock, 5 final cross-bred commercial layer populations (white-, tinted-, and brown-egg layers), and 2 final cross-bred commercial broiler populations were genotyped for 40 autosomal microsatellite loci. We compared microsatellite variations in Red Junglefowl with those in a commercial chicken gene pool. The contribution of each population to the genetic diversity was also estimated based on the molecular coancestry. In total, 302 distinct alleles were detected in 1 Red Junglefowl and 7 commercial chicken populations, of which 31 alleles (10.3%) were unique to Red Junglefowl, most of which occurred at a high frequency. The genetic differentiation between Red Junglefowl and commercial chickens (pairwise FST) ranged from 0.32 to 0.47. According to the neighbor-joining tree based on the modified Cavalli-Sforza chord distances and the Bayesian clustering analysis, Red Junglefowl was genetically distant from the commercial chicken gene pool tested. In all of the populations analyzed, Red Junglefowl made the highest contribution to genetic diversity. These results suggest that Red Junglefowl has a distinct distribution of microsatellite alleles and that there is a high level of genetic divergence between Red Junglefowl and commercial chickens.

Understanding Darjeeling tea flavour on a molecular basis.

Darjeeling teas are the highest grown teas in the world and preferred for its flavour, aroma and quality. Apart from the genetic makeup of the plant, earlier reports suggest that insect infestation, particularly jassids and thrips triggers the aroma and flavour formation in Darjeeling tea. The present work encompasses the identification of the genes/transcriptomes responsible for the typical flavour of Darjeeling tea, besides understanding the role of jassids and thrips in particular, in producing the best cup character and quality. The quantitative real time PCR analysis was based on a suppression subtractive hybridisation forward library of B157 (tea clone infested with thrips), providing us transcripts related to aroma and flavour formation. We observed the expression of genes like leucine zipper, ntd, nced, geraniol synthase, raffinose synthase, trehalose synthase, amylase, farnesyl transferase, catalase, methyl transferase, linalool synthase, peroxidases, elicitor responsive proteins, linamarase, nerolidol linalool synthase 2, 12-oxophytodienoate reductase, glucosidase, MYB transcription factor, and alcohol dehydrogenase, highly regulated due to insect infestation, manufacturing stresses and mechanical injury. The first report on gene expression dynamics in thrips infested Darjeeling tea leaves can be extrapolated with increase in volatiles which is responsible for enhancing the quality of Darjeeling tea, specially the flavour and aroma of the infusion. We hope to model these responses in order to understand the molecular changes that occur during Darjeeling tea flavour formation.

High genetic divergence in miniature breeds of Japanese native chickens compared to Red Junglefowl, as revealed by microsatellite analysis.

A wide diversity of domesticated chicken breeds exist due to artificial selection on the basis of human interests. Miniature variants (bantams) are eminently illustrative of the large changes from ancestral junglefowls. In this report, the genetic characterization of seven Japanese miniature chicken breeds and varieties, together with institute-kept Red Junglefowl, was conducted by means of typing 40 microsatellites located on 21 autosomes. We drew focus to genetic differentiation between the miniature chicken breeds and Red Junglefowl in particular. A total of 305 alleles were identified: 27 of these alleles (8.9%) were unique to the Red Junglefowl with high frequencies (>20%). Significantly high genetic differences (F(ST)) were obtained between Red Junglefowl and all other breeds with a range of 0.3901-0.5128. Individual clustering (constructed from combinations of the proportion of shared alleles and the neighbour-joining method) indicated high genetic divergence among breeds including Red Junglefowl. There were also individual assignments on the basis of the Bayesian and distance-based approaches. The microsatellite differences in the miniature chicken breeds compared to the presumed wild ancestor reflected the phenotypic diversity among them, indicating that each of these miniature chicken breeds is a unique gene pool.

Transcutaneous electrical nerve stimulation at the PC-5 and PC-6 acupoints reduced the severity of hypotension after spinal anaesthesia in patients undergoing Caesarean section.

BACKGROUND: Despite prophylactic measures, hypotension remains a common side-effect of spinal anaesthesia for parturients. Electroacupuncture at the Neiguan (PC-6) and Jianshi (PC-5) points influences haemodynamics. We thus hypothesized that transcutaneous electrical nerve stimulation (TENS) at traditionally used acupuncture points would reduce the severity of hypotension after spinal anaesthesia in patients undergoing Caesarean section. METHODS: After obtaining approval from the local ethics committee and written informed patient consent, 36 singleton parturients undergoing Caesarean section under spinal anaesthesia were randomized into three groups. The control group received no treatment, and the acupoint and non-acupoint groups received TENS at the PC-5 and PC-6 points of both arms and non-acupoints of both shoulders, respectively. RESULTS: The median (range) of the lowest recorded systolic blood pressure was significantly higher in the acupoint group compared with the other groups and that of the non-acupoint group was higher than that of the control group [control, 70 (68-82) mm Hg; acupoint, 94 (84-109) mm Hg; non-acupoint, 81 (70-92) mm Hg: P<0.001]. Significantly more parturients in the control and non-acupoint groups experienced hypotension [control, 10 (83%); acupoint, 4 (33%); non-acupoint, 10 (83%): P=0.013]. More ephedrine was required to maintain arterial blood pressure in the control and non-acupoint groups. CONCLUSIONS: TENS on the traditional acupuncture points reduced the severity and incidence of hypotension after spinal anaesthesia in parturients.

Induction and emergence behavior of children undergoing general anesthesia correlates with maternal salivary amylase activity before the anesthesia.

BACKGROUND: The parents of the children who undergo surgery experience stress during the pre-anesthetic period. Such stress influences the mental status of their children, thereby inducing their pre-anesthetic anxiety and problematic behavior at emergence. Recently, measurement of salivary biomarkers was evaluated as stress biomarkers. Especially, alpha-amylase is utilized as an excellent index for psychological stress. In the present study, we tested whether salivary amylase activity of mothers before the surgery of their children correlates with the peri-operative children's behaviors. METHODS: A total of 22 pairs of mothers and children were analyzed. Maternal salivary amylase activity was evaluated at the entrance of the operation room. The children underwent minor plastic surgery under general anesthesia, and induction and emergence behaviors were assessed. RESULTS: The higher the maternal salivary amylase activity, the severer the children's induction anxiety (r(s)=-0.667, n=22, P<0.0001), and the higher the maternal amylase activity, the severer the children's emergence agitation (r(s)=0.705, n=22, P<0.0001). CONCLUSION: Induction and emergence behaviors of children undergoing general anesthesia significantly correlated with their respective maternal salivary amylase activity during the pre-anesthetic period.

Blunt renal trauma: comparison of contrast-enhanced CT and angiographic findings and the usefulness of transcatheter arterial embolization.

BACKGROUND: The purpose of this study was to evaluate the role of contrast-enhanced CT and the usefulness of superselective embolization therapy in the management of arterial damage in patients with severe blunt renal trauma. PATIENTS AND METHODS: Nine cases of severe renal trauma were evaluated. In all cases, we compared contrast-enhanced CT findings with angiographic findings, and performed transcatheter arterial embolization (TAE) in six of them with microcoils and gelatin sponge particles. Morphological changes in the kidney and site of infarction after TAE were evaluated on follow-up CT Chronological changes in blood biochemistry findings after injury, degree of anemia and renal function were investigated. Adverse effects or complications such as duration of hematuria, fever, abdominal pain, renovascular hypertension and abscess formation were also evaluated. RESULTS: The CT finding of extravasation was a reliable sign of active bleeding and useful for determining the indication of TAE. In all cases, bleeding was effectively controlled with superselective embolization. There was minimal procedure-related loss of renal tissue. None of the patients developed abscess, hypertension or other complications. CONCLUSIONS: In blunt renal injury, contrast-enhanced CT was useful for diagnosing arterial hemorrhage. Arterial bleeding may produce massive hematoma and TAE was a useful treatment for such cases. By using selective TAE for a bleeding artery, it was possible to minimize renal parenchymal damage, with complications of TAE rarely seen.

Potential application of sperm bearing female-specific chromosome in chickens.

This paper reviews studies on sex reversal experiments in chickens, production of sperm bearing a female-specific chromosome, its application for poultry resources and finally a mechanism of sex differentiation of gonads in the chicken.

Endothelin receptor B2 (EDNRB2) is associated with the panda plumage colour mutation in Japanese quail.

The panda mutant in Japanese quail (Coturnix japonica) displays spots of wild-type plumage on a white background and is controlled by an autosomal recessive allele (s). The dotted white is controlled by a third allele (s(dw)) of the s locus with s(dw)/s(dw) quail having less pigmentation than s/s quail. We mapped the s locus to the Japanese quail chromosome 4 (CJA04) in a previous study. The orthologous region of the chicken (Gallus gallus) genome includes endothelin receptor B2 (EDNRB2), an avian-specific paralog of endothelin receptor B (EDNRB). EDNRB mutations in mammals retard the migration of neural crest cells (NCCs), which results in a spotted coat colour and an enteric nervous defect. In the present study, we investigated the association between the s locus and EDNRB2 in Japanese quail. Sequence comparison among transcripts from livers of wild-type, panda and dotted white quail revealed a nucleotide substitution (c.995G>A) leading to a p.R332H amino acid change that was specific to panda, whereas no amino acid substitution was found in dotted white birds. The amino acid position 332 is located in the sixth transmembrane domain and is highly conserved in both avian and mammalian endothelin receptors. The A allele at nucleotide position 995 was specific to panda (s/s) birds among 10 strains, and was mapped to the same chromosomal region as the s locus. Quantitative RT-PCR revealed that EDNRB2 transcripts were reduced in both panda and dotted white mutants compared with wild-type. However, there was no difference between the early embryos of wild-type and panda with respect to the migration of NCCs. The genetic association of EDNRB2 with plumage colour in birds was found for the first time in this study.