Delineating developmental and metabolic pathways in vivo by expression profiling using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays

We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.     

A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature

Congenital high airway obstruction syndrome (CHAOS) has been reported to be fatal. Ten cases of CHAOS that underwent ex utero intrapartum treatment (EXIT) procedure to secure the fetal airway have been reported. A 36-year-old woman (gravida 3, para 2) was referred to our hospital at 22 weeks of gestation. Sonography revealed large echogenic lungs, flattened diaphragm, and marked hydrops. Magnetic resonance imaging confirmed the diagnosis of CHAOS. Polyhydramnios and fetal skin edema were improved and the fetal ascitic fluid was regressed gradually. At 36 weeks of gestation, an EXIT procedure was undertaken. Fetal laryngoscopy and bronchoscopy showed complete laryngeal obstruction, and a tracheostomy was performed immediately. The infant was discharged from hospital at 6 weeks of age. Thereafter, he developed well both physically and mentally. A laryngoplasty was performed at 20 months of age using silicon sheet as a patent airway. The child has a tracheostomy, is able to phonate but does not speak, and is awaiting decannulation. Use of the EXIT procedure in CHAOS cases offers the potential for salvage and excellent long-term outcome of these fetuses that otherwise would not survive. However, management of the airway, particularly with regard to long-term reconstruction in children with CHAOS, remains challenging.     

Predictive model for recurrence of renal cell carcinoma by comparing pre‐ and postoperative urinary metabolite concentrations

To improve treatment outcomes in real practice, useful biomarkers are desired when predicting postoperative recurrence for renal cell carcinoma (RCC). We collected data from patients who underwent definitive surgery for RCC and for benign urological tumor at our department between November 2016 and December 2019. We evaluated the differences in pre‐ and postoperative urinary metabolites with our precise quantitative method and identified predictive factors for RCC recurrence. Additionally, to clarify the significance of metabolites, we measured the intracellular metabolite concentration of three RCC cell lines. Among the 56 patients with RCC, nine had a recurrence (16.0%). When comparing 27 patients with T1a RCC and 10 with benign tumor, a significant difference was observed between pre‐ and postoperative concentrations among 10 urinary metabolites. In these 10 metabolites, multiple logistic regression analysis identified five metabolites (lactic acid, glycine, 2‐hydroxyglutarate, succinic acid, and kynurenic acid) as factors to build our recurrence prediction model. The values of area under the receiver operating characteristic curve, sensitivity, and specificity in this predictive model were 0.894%, 88.9%, and 88.0%, respectively. When stratified into low and high risk groups of recurrence based on this model, we found a significant drop of recurrence‐free survival rates among the high risk group. In in vitro studies, intracellular metabolite concentrations of metastatic tumor cell lines were much higher than those of primary tumor cell lines. By using our quantitative evaluation of urinary metabolites, we could predict postoperative recurrence with high sensitivity and specificity. Urinary metabolites could be noninvasive biomarkers to improve patient outcome.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Accurate quantification of urinary metabolites for predictive models manifest clinicopathology of renal cell carcinoma

Using surgically resected tissue, we identified characteristic metabolites related to the diagnosis and malignant status of clear cell renal cell carcinoma (ccRCC). Specifically, we quantified these metabolites in urine samples to evaluate their potential as clinically useful noninvasive biomarkers of ccRCC. Between January 2016 and August 2018, we collected urine samples from 87 patients who had pathologically diagnosed ccRCC and from 60 controls who were patients with benign urological conditions. Metabolite concentrations in urine samples were investigated using liquid chromatography‐mass spectrometry with an internal standard and adjustment based on urinary creatinine levels. We analyzed the association between metabolite concentration and predictability of diagnosis and of malignant status by multiple logistic regression and receiver operating characteristic (ROC) curves to establish ccRCC predictive models. Of the 47 metabolites identified in our previous study, we quantified 33 metabolites in the urine samples. Multiple logistic regression analysis revealed 5 metabolites (l ‐glutamic acid, lactate, d ‐sedoheptulose 7‐phosphate, 2‐hydroxyglutarate, and myoinositol) for a diagnostic predictive model and 4 metabolites (l ‐kynurenine, l ‐glutamine, fructose 6‐phosphate, and butyrylcarnitine) for a predictive model for clinical stage III/IV. The sensitivity and specificity of the diagnostic predictive model were 93.1% and 95.0%, respectively, yielding an area under the ROC curve (AUC) of 0.966. The sensitivity and specificity of the predictive model for clinical stage were 88.5% and 75.4%, respectively, with an AUC of 0.837. In conclusion, quantitative analysis of urinary metabolites yielded predictive models for diagnosis and malignant status of ccRCC. Urinary metabolites have the potential to be clinically useful noninvasive biomarkers of ccRCC to improve patient outcomes.     

A case of scirrhous gastric cancer with peritonitis carcinomatosa controlled by TS-1(R) + paclitaxel for 36 mo after diagnosis

A 34-year-old female complaining of abdominal fullness was diagnosed as scirrhous gastric cancer (type 4')with peritonitis carcinomatosa in July 2002. A combined chemotherapy regimen was selected to control massive ascites; TS-1(R) 80 mg/m2 was given orally on d 1-14,22-35, and paclitaxel 50 mg/m2 was administered intravenously on d 1, 8, 22 and 29. After 2 courses of this regimen, the primary tumor was markedly reduced,and ascites completely vanished. Alopecia (grade 1,since d 30), leukocytopenia (grade 2, on d 34) and anemia (grade 2, on d 34) were the only adverse events throughout the following courses. The chemotherapy was effective for 28 mo, and then it was discontinued upon the patient's own request, and she survived for 36mo after diagnosis.     

Late stent thrombosis in patients receiving ticlopidine and aspirin after sirolimus-eluting stent implantation.

BACKGROUND: There is little information about the efficacy of ticlopidine plus aspirin after sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: The incidence of stent thrombosis was evaluated in 1,029 patients receiving ticlopidine and aspirin after SES deployment. Clinical follow-up was obtained in 98.9% (mean follow-up 17.0+/-7.9 months). Early stent thrombosis was observed in 5 patients (0.49%). There was 1 case each of late (0.1%) and very late stent thrombosis (0.1%). CONCLUSION: Late and very late stent thrombosis in Japanese patients receiving ticlopidine and aspirin after SES deployment occurs infrequently.