Design and implementation of an adaptive confirmatory trial in Japanese patients with palmoplantar pustulosis.

Background/aims: More and more literature describes how to overcome challenges in the implementation of adaptive designs for trials for drug approval process. Most adaptive trials were conducted in Western Europe or USA for Phase II or Phase II/III settings; however, examples of non-oncology pivotal adaptive trials used for regulatory approval in Japan are rare. This article elaborates on our experience with designing and implementing a Phase III adaptive confirmatory trial permitting unblinded sample size re-estimation and futility analysis after a single interim analysis in Japanese patients with palmoplantar pustulosis (PPP) receiving guselkumab.

Feeding of 1-Kestose Induces Glutathione-S-Transferase Expression in Mouse Liver.

Functional food ingredients, including prebiotics, have been increasingly developed for human health. The improvement of the human intestinal environment is one of their main targets. Fructooligosaccarides (FOS) are oligosaccharide fructans that are well studied and commercialized prebiotics.

Successful treatment of bortezomib-refractory multiple myeloma derived from monoclonal gammopathy of undetermined significance with dose-adjusted lenalidomide therapy in a patient with concomitant end-stage renal disease due to diabetic nephropathy requiring haemodialysis.

Malignancy is a fatal complication of end-stage renal disease (ESRD) requiring haemodialysis. However, the successful treatment of haematological malignancies has been rarely reported. We describe the case of a 63-year-old man who presented with IgA-type multiple myeloma (MM; Durie-Salmon stage IIIB) derived from monoclonal gammopathy of undetermined significance concomitant with ESRD due to diabetic nephropathy.

Influence of the galloyl moiety in tea catechins on binding affinity for human serum albumin.

The major catechins of green tea extract are (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg). Recent research has indicated that catechins form complexes with human serum albumin (HSA) in blood, and differences in their binding affinity toward HSA are believed to modulate their bioavailability. In this study, we kinetically investigated the interaction between the catechins and HSA immobilized on a quartz-crystal microbalance (QCM).

Human serum albumin as an antioxidant in the oxidation of (-)-epigallocatechin gallate: participation of reversible covalent binding for interaction and stabilization.

Human serum albumin (HSA) contributes to the stabilization of (-)-epigallocatechin gallate (EGCg) in serum. We characterize in the present study the mechanisms for preventing EGCg oxidation by HSA. EGCg was stable in human serum or buffers with HSA, but (-)-epigallocatechin (EGC) was unstable.

Binding affinity of tea catechins for HSA: characterization by high-performance affinity chromatography with immobilized albumin column.

Catechins are the major polyphenols in green tea leaves. Recent studies have suggested that the catechins form complexes with HSA for transport in human blood, and their binding affinity for albumin is believed to modulate their bioavailability. In this study, the binding affinities of catechins and their analogs were evaluated and the relationship between the chemical structure of each catechin and its binding property were investigated.

Functional new acylated sophoroses and deglucosylated anthocyanins in a fermented red vinegar.

The new acylated polyphenols were isolated from a red-colored vinegar produced via fermentation with purple-fleshed sweet potato storage roots, and identified mainly by MS and NMR. The three acylated sophoroses were determined as 6-O-(E)-caffeoyl-(2-O-(6-O-acyl)-beta-d-glucopyranosyl)-d-glucopyranoses, where acyl was (E)-caffeoyl, p-hydroxybenzoyl, and (E)-feruloyl, respectively. The four acylated anthocyanins were also determined as cyanidin 3-O-(6-O-(E)-caffeoyl-(2-O-(6-O-(E)-feruloyl)-beta-d-glucopyranosyl)-beta-d-glucopyranoside), in addition to peonidin 3-O-(6-O-(E)-caffeoyl-(2-O-(6-O-acyl)-beta-d-glucopyranosyl)-beta-d-glucopyranosides), where acyl was (E)-caffeoyl, p-hydroxybenzoyl, and (E)-feruloyl, respectively.

Albumin stabilizes (-)-epigallocatechin gallate in human serum: binding capacity and antioxidant property.

(-)-Epigallocatechin gallate (EGCg) is the major component of green tea and is known to show strong biological activity, although it can be easily oxidized under physiological conditions. In this study, we indicate that EGCg is stable in human serum and that human serum albumin (HSA) stabilizes EGCg under aerobic condition. Although EGCg is usually decomposed within 1 h in aqueous solution at neutral pH, EGCg in serum and phosphate buffer (pH 7.

Antiviral activity of berberine and related compounds against human cytomegalovirus.

Berberine chloride (1) and the structurally related compounds were assessed for the anti-human cytomegalovirus (HCMV) activity using the plaque assay. The anti-HCMV activity (IC(50) 0.68 microM) of 1 was equivalent to that (IC(50) 0.

Changes in cerebral blood flow under the prone condition with and without massage.

To investigate changes in regional cerebral blood flow (rCBF) under the prone condition with and without light massage on the back, we measured rCBF quantitatively in healthy human subjects using positron emission tomography with H(2)15O. Biochemical tests showed that the light massage (palm-pressure) reduced levels of stress-related serum cortisol and salivary stress protein chromogranin-A measured after the PET examination. Absolute rCBF significantly increased in the parietal cortex (precuneus) under the prone condition compared with the supine condition, and this rCBF increase was in parallel with comfortable sensation and slowing heart rate during the massage.

Preliminary study: psychological effects of muscle relaxation on juvenile delinquents.

The purpose of this study is to test our hypothesis that muscle relaxation is effective on the psychological well-being of juvenile delinquents. Subjects were 16 juvenile delinquents who had entered a reform school. Subjects were divided into two groups.

Laterality and imbalance of muscle stiffness relate to personality.

The authors' purpose in this study was to test the hypothesis that laterality and imbalance of muscle stiffness relate to personality. The authors selected 23 healthy volunteers and divided them into two groups based on the predominance of muscle stiffness on the left or right side. Imbalance of muscle stiffness was calculated as the absolute value of the difference of muscle stiffness between the right and left sides.

Hypermethylation in the retinoblastoma gene is associated with unilateral, sporadic retinoblastoma.

We previously reported 9 unilateral, sporadic retinoblastomas with hypermethylation in the 5' region of the RB gene, and we found that CpG methylation in the RB promoter inhibits the binding of the retinoblastoma binding factor 1 (RBF-1) and the activating transcription factor (ATF)-like factors, thereby resulting in a considerable reduction in RB promoter activity. In this study, we screened for hypermethylation in 121 additional cases of retinoblastoma, and found 5 tumors with hypermethylation, including 4 unilateral, sporadic tumors, and one hereditary tumor. The hereditary tumor had a germline deletion of one allele, and the hypermethylation was an acquired, epigenetic change in the other allele.

Exon-by-exon screening for RB germline mutations using Heteroduplex-SSCP analysis.

Objective: To disclose the nature of RB1 germline mutations in Chinese and to develop a practical and effective way for mutational screening.

Methods: Leukocyte DNA was prepared from 8 Chinese patients with hereditary retinoblastoma. PCR combined with nonisotopic heteroduplex-SSCP analysis was used to screen leukocyte DNA for RB1 germline mutations, exon-by-exon, without the use of restriction endonuclease digestion.

Detection of RB germline mutations using exon-by-exon heteroduplex analysis compared with SSCP.

Purpose: To compare heteroduplex analysis with SSCP and to develop a simple and effective method for mutational screening of RB gene.

Materials And Methods: Leukocyte DNA was prepared from 12 unrelated Japanese patients with hereditary retinoblstoma. PCR combined with simultaneous nonisotopic heteroduplex and SSCP analysis was used to screen leukocyte DNA for such mutations, exon-by-exon, without the use of restriction endonuclease digestion.

Single 5'green-3'red hybrid gene in protanopia.

Purpose: To disclose the structure of visual pigment gene for a protanopia with specific variation.

Methods: Exon 5 fragments of the red and green visual pigment genes from the protanopia with specific variation as well as controls were amplified by polymerase chain reaction (PCR). The PCR products were put through heteroduplex-SSCP analysis and PCR-RFLP (restriction fragment length polymorphism) analysis to clarify the specific variation.

Detection of congenital color vision defects using heteroduplex-SSCP analysis.

Gene deletion and hybrid gene formation result in congenital red and green color vision defects. The innumerable variations in these defects require the development of appropriate methods for detailed investigation. We used heteroduplex-single-strand conformation polymorphism (SSCP) analysis to detect the gene variations in subjects with congenital red and green color vision defects.

[Genetics of retinoblastoma].

Recent advancement of molecular genetics has enabled us to perform presymptomatic prediction for hereditary retinoblastoma, based on RB gene diagnosis. We used PCR combined with SSCP and heteroduplex analysis to screen leukocyte DNA, exon by exon, in patients with bilateral retinoblastoma. Germline mutations were detected in the 22 of the 33 cases, and, in 16 cases, the mutations were identified by sequencing.

[Ectopic ureterocele in a male adult: a case report].

A case of ectopic ureterocele in a 21-year-old male is reported. His chief complaint was right flank pain. We diagnosed ectopic ureterocele in right complete ureteric duplication with upper pole and right heminephrectomy was performed.

Mutation detection and genetic counseling in retinoblastoma using heteroduplex analysis.

Gene diagnosis is essential for confident presymptomatic prediction, genetic counseling, and early management of hereditary retinoblastoma. In screening the leukocyte DNA of three patients with bilateral retinoblastoma for RB1-gene heterozygous germline mutations, we identified mutations involving exon 3 or 18 of the RB1 gene by using heteroduplex analysis and sequencing. In one case the mutation was a 2 bp GT deletion resulting in the loss of the exon 18 splicing-donor; another mutation was a G-to-T transversion at codon 580 in exon 18, which converts Arg to a stop codon.

Photoreceptor differentiation of retinoblastoma: an electron microscopic study of 29 retinoblastomas.

Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.

Comparison of the distribution of myocardial blood flow between exercise-induced and hyperventilation-induced attacks of coronary spasm: a study with thallium-201 myocardial scintigraphy.

Exercise and hyperventilation tests are often used as the provocative tests for coronary artery spasm. To examine the distribution of myocardial blood flow during exercise-induced and hyperventilation-induced attacks of coronary spasm, thallium-201 myocardial scintigraphy was performed in 47 patients with variant angina. The extent and severity scores and severity index (severity score/extent score) of scintigraphic perfusion defect were calculated.

Influence of exercise-induced coronary artery spasm on thallium-201 initial distribution and washout kinetics in patients with variant and classic angina pectoris.

Thallium-201 single-photon emission computed tomography was performed immediately, and 2 and 4 hours after exercise-induced anginal attack in 2 groups of patients with either exercise-induced coronary spasm or severe fixed stenosis on the isolated proximal left anterior descending coronary artery. All patients with variant angina had transient ST-segment elevation during the exercise-induced attack for thallium-201 scintigraphic study. Both perfusion defects and 4-hour washout abnormalities were significantly greater in patients with variant angina than in those with stable effort angina (p < 0.