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Two new octaketides, trichoketides A (1) and B (2), were isolated from a culture broth of the seawater-derived fungus Trichoderma sp. TPU1237 together with two known analogs, trichodermaketones C (3) and D (4), by ODS column chromatography followed by preparative ODS and chiral HPLC. The structures of 1 and 2 were elucidated on the basis of their spectroscopic data, and absolute configurations were assigned by comparing their experimental electronic circular dichroism (ECD) spectra with the calculated ECD spectra. Compounds 1 and 2 were epimers at the C-8 position (α-position of dihydrofuran ring). The IC50 values of compounds 1-4 against protein tyrosine phosphatase 1B were 53.1, 65.1, 68.0 and 55.9 μM, respectively.

Two new merosesquiterpenes, verruculides A (1) and B (2), were isolated from a culture broth of the Indonesian ascidian-derived Penicillium verruculosum TPU1311, together with three known congeners, chrodrimanins A (3), B (4), and H (5). The structures of 1 and 2 were assigned on the basis of their spectroscopic data (1D and 2D NMR, HRMS, UV, CD, and IR). Compound 2 had a linear sesquiterpene moiety and was considered to be the derivative of the biosynthetic precursor for 1 and 3-5. Compounds 1, 3, and 5 inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 8.4, 8.5, and 14.9 μM, respectively. Compound 2 showed 40% inhibition at 23.1 μM, while 4 was not active at 20.7 μM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Combination drugs containing an angiotensin receptor blocker and a calcium channel blocker have been widely commercialized in recent years, and their advantages, such as improvements in adherence, and reductions in medication costs, have been greatly emphasized. However, the actual situations and the impact of switching to combination drugs in clinical practice of nephrology are not fully understood., Methods: This study was conducted in outpatients of nephrology who received antihypertensive medicines, and who switched to combination drugs. Changes in the potency of the antihypertensive drugs, and blood pressure were examined retrospectively before and after changing treatments. In addition, the study also involved patients' questionnaire, which examined changes in blood pressure at home, the presence or absence of missed doses, the impact on medication-related expenses, and the level of patients' satisfaction with regard to combination drugs., Results: Survey results from 90 participants revealed that changing to combination drugs resulted in a reduction of missed doses, a decrease in blood pressure measured in an outpatient setting, and a reduction in medication-related expenses in total patients, non-chronic kidney disease (CKD) patients, and CKD patients., Conclusion: Our study shows that switching to combination antihypertensive drugs resulted in an improvement in adherence and a reduction in medication-related expenses, and revealed that patient satisfaction was high. Combination drugs for hypertensive patients may be beneficial in both medical and economical viewpoints.

Sanfilippo type B syndrome (mucopolysaccharidosis type IIIB; MPS IIIB) is an autosomal recessive lysosomal storage disorder that is caused by defective alpha- N-acetylglucosaminidase (NAGLU). We performed NAGLU gene analysis in five patients with MPS IIIB whose respective parents from the Okinawa islands in Japan were not apparently consanguineous. We found a missense mutation (R565P) in all five patients (all homozygotes). We screened this mutation in 200 healthy subjects and found one heterozygote (none of the subjects were related to the patients). These results suggest that there may be a founder effect that results in the accumulation of R565P mutation in this area.

Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, Robin sequence, abnormally shaped ears, cardiac defect, and hypotonia. We describe two Japanese sisters with a Toriello-Carey syndrome whose phenotypes were as severe as reported male cases. The younger sister died suddenly at age 4 months. Our patients with a severe phenotype and possible parental consanguinity suggest autosomal recessive inheritance of Toriello-Carey syndrome., (Copyright 1999 Wiley-Liss, Inc.)

We reported on two patients with a de novo marker chromosome of which the origins were successfully identified by FISH using microdissected probes. These probes were established by microdissections of extra chromosomal segments from Carnoy-fixed cells stored at -20 degrees C for several years. Using these probes, we could verify partial 1q32 trisomy in a patient with 17p+ as well as partial 16q2 trisomy in another patient with 4p+.

We report on a female infant with an interstitial deletion involving 2q24.3. She had multiple congenital anomalies similar to those in patients with del(2)(q31q33) except for an occipital encephalocele. As a result of comparison of clinical findings among interstitial 2q deletions, a distinct 2q medial monosomy syndrome may be delineable in association with a deletion of 2q31.

To obtain direct evidence for a molecular basis of differentiation between regular Giemsa dark (G)- and light (R)-band regions of human chromosomes, two regions of chromosome 11, q14-q22 (G-band) and q23-q25 (R-band), were microdissected. The DNA fragments were amplified by the linker-primer polymerase chain reaction and cloned into pUC19. Microclones from each library were then compared by colony hybridization with repetitive DNA sequences, by Southern blot hybridization of each microclone to total human genomic DNA and mouse-human hybrid cell DNA containing only human chromosome 11, and by sequencing of unique and Alu-repetitive clones. Among the G-band-derived microclones analyzed, 43.0% were single-copy (unique) sequences and 23.2% contained highly repetitive sequence elements; in the R-band-derived library, 54.2% were unique clones and 20.3% had highly repetitive elements. The G-band library was significantly richer in clones positive for KpnI sequences (4.1% in the G-band library vs 2.8% in the R-band library). No significant difference was found in the proportion of Alu repetitive clones present in the two libraries, but Class IV Alu sequence derivatives were more frequently observed in the R-library than in the G-library. Sequence analysis revealed no significant difference in GC content or in the ratio of CpG sequence to GpC dinucleotide between 30 microclones derived from G-bands and 29 microclones derived from R-bands.(ABSTRACT TRUNCATED AT 250 WORDS)

A 3-year-old boy with Costello syndrome is reported. He had typical clinical features of the syndrome including severe postnatal growth retardation, poor sucking, mild developmental delay, a coarse characteristic facies, thick and loose skin of the hands and feet, sparse and curly hair, dark skin, and relative macrocephaly but lacked nasal papillomas. In addition, he had cardiac anomalies with extrasystoles and thick mitral valve tips. Mitral valve defects may be a clinical feature of the syndrome.

An inverted insertion of a segment 7q22-q34 into 3q21 was found in a mentally normal male infant with ectrodactyly of a hand and the feet. A putative gene for ectrodactyly seems to be assigned at 7q22.

A 10-year-old girl and a 10-month-old girl, both with ambiguous genitalia, were found to have 45,X/46,X,mar and 45,X/46,X,r(?) mosaicism. The marker chromosomes in both girls were very small. Polymerase chain reaction, with synthetic oligonucleotide primers from Y-specific DNA sequences pY-80 and pY53.3 containing the sex-determining region Y(SRY), proved the marker chromosomes to contain the Y short arm material. In situ hybridization with probe pY-80 confirmed that the marker chromosomes included the Y short arms. These findings, together with ambiguous genitalia in the girls, indicate that the marker chromosomes include the testis-determining factor gene.

We report on 2 girls with a terminal deletion of the short arm of chromosome X. They had microphthalmia, cloudy corneae, mild linear skin lesions, and agenesis of corpus callosum. A comparison of clinical and cytogenetic findings in similar cases suggested that the critical genes for the Goltz and Aicardi syndromes might be contiguous in the region Xp22.31.

We report clinical and cytogenetic findings of 4 children (2 boys and 2 girls) with the Smith-Magenis syndrome. All 4 patients had an interstitial deletion of 17p: del(17) (p11.2p11.2). Their clinical manifestations included brachycephaly, midface hypoplasia, prognathism, upper lip eversion, short and broad hands with short fingers, clinodactyly of the fifth fingers, fingertip pads, moderate mental retardation, and behavior problems. Analysis of the metacarpophalangeal pattern profiles in patient 2 showed progressive shortness from the metacarpals to the proximal, middle, and the distal phalanges. The fingerpads observed in all 4 patients have hitherto been noted in only one of 26 previously reported patients with the syndrome. These findings serve as a useful clue to the diagnosis of the syndrome.

DNA deletion studies using 5 DNA markers localized at 15q11-q12 were performed in 14 Angelman syndrome (AS) patients (9 sporadic and 5 familial cases). A one-copy density for one or more of the 5 loci was detected in 8 (57.1%) of the 14 patients. A deletion of only the D15S11 locus was detected in one sporadic patient, that involving only the D15S10 in 3 familial patients (sibs in a family), that spanning 3 loci (D15S11, D15S10, D15S12) in one sporadic patient, and that spanning 4 loci (D15S9, D15S11, D15S10, D15S12) in the other 3 sporadic patients. The deletion common to our patients as well as to the reported patients may be confined to a segment between D15S11 and D15S10, if the 5 loci are ordered as cen-D15S18-(D15S9-D15S11-D15S10)-D15S12-qt er. This site overlaps but is more distal to the common deletion site in Prader-Willi syndrome (PWS) patients. In the family of the 3 sibs, both of the phenotypically normal mother and maternal grandfather also have deletions of the D15S10 locus. These results were consistent with the genomic imprinting hypothesis for the occurrence of AS, i.e., the lack of a maternally derived locus leads to AS, but may not support a model that AS is the alternative phenotype of PWS at the identical locus.

Replication kinetics of the Prader-Willi syndrome critical region (15q11.2) was investigated in seven normal healthy adult females using RBG replication bands. Replication asynchrony between homologs 15q11.2 was identified consistently in about 40% of cells in all individuals. It was limited to the stages in which Xp22, Xp11, Xq13 and Xq24/26 were visible in the late-replicating X chromosome. This asynchrony suggested that replication timing overlapped between 15q11.2 and the early replicating R-bands of the late X chromosome in some cells, and that the difference in replication timing between homologs was probably related to genomic imprinting; the latter has been suggested as a pathogenetic basis of Prader-Willi syndrome. As a result of an analysis of the proportions of asynchronous and synchronous cells in each replication stage, two types of cells were deduced providing 1:1 methylation mosaicism of genomic imprinting was assumed. The first type was composed of cells with normal replication in one homolog and delayed replication in the other. The second type was composed of cells with normal replication in both homologs. Our results provide cytogenetic evidence of methylation mosaicism for mammalian genomic imprinting.