Characteristics of histologically confirmed endometriosis in cynomolgus monkeys.

STUDY QUESTION: What are the characteristics of spontaneous endometriosis in cynomolgus monkeys? SUMMARY ANSWER: Spontaneous endometriosis in cynomolgus monkeys exhibited similar characteristics to the human disease. WHAT IS KNOWN ALREADY: One previous report described the prevalence and the basic histopathology of spontaneous endometriosis in cynomolgus monkeys. STUDY DESIGN, SIZE, DURATION: Endometriotic lesions that had been histologically confirmed in 8 female cynomolgus monkeys between 5 and 21 years old were subjected to study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The monkeys died of, or were sacrificed because of, sickness consequent on endometriosis. Specimens were evaluated histopathologically with haematoxylin and eosin staining, iron staining and immunohistochemistry (CD10, CD31, α-SMA and PGP9.5), and by observing them under a microscope. MAIN RESULTS AND THE ROLE OF CHANCE: Endometriotic and stromal cells (CD10-positive) with haemorrhage and inflammation were observed. Smooth muscle metaplasia and nerve fibres were also noted in the endometriotic lesions. Endometriotic lesions in lymph nodes were incidentally found. LIMITATIONS AND REASONS FOR CAUTION: Since laparoscopic analysis for monitoring the disease state was not set as a parameter of the current study, time course changes (progression) of the disease were not assessed. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation of spontaneous endometriosis in cynomolgus monkeys may contribute to better understanding of the disease pathobiology. STUDY FUNDING/COMPETING INTERESTS: No external funds were used for this study. A.N.K., S.M., S.H., T.I., O.K., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received lecture fees from Chugai Pharmaceutical Co., Ltd., unrelated to the submitted work. S.N., S. O., L.Y., K.Y. and T.S. have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 2.

Highly potent 1,3-beta-D-glucan synthase inhibitors, 7b, 10a, 10b and 12, have been identified by the chemical modification of the ornithine residue of a fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. These compounds showed stronger antifungal activity against systemic candidiasis as well as pulmonary aspergillosis in mice, and less hepatotoxicity as compared with 1.

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1.

Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.

Familial isolated noncompaction of ventricular myocardium.

We report a family in which two male sibs were affected with isolated noncompaction of ventricular myocardium (INVM). The familial occurrence of INVM suggests a genetic basis. We review the literature of familial and nonfamilial cases and discuss the inheritance pattern of INVM.

Cloning of the RHO1 gene from Candida albicans and its regulation of beta-1,3-glucan synthesis.

The Saccharomyces cerevisiae RHO1 gene encodes a low-molecular-weight GTPase. One of its recently identified functions is the regulation of beta-1,3-glucan synthase, which synthesizes the main component of the fungal cell wall (J. Drgonova et al., Science 272:277-279, 1996; T. Mazur and W. Baginsky, J. Biol. Chem. 271:14604-14609, 1996; and H. Qadota et al., Science 272:279-281, 1996). From the opportunistic pathogenic fungus Candida albicans, we cloned the RHO1 gene by the PCR and cross-hybridization methods. Sequence analysis revealed that the Candida RHO1 gene has a 597-nucleotide region which encodes a putative 22.0-kDa peptide. The deduced amino acid sequence predicts that Candida albicans Rho1p is 82.9% identical to Saccharomyces Rho1p and contains all the domains conserved among Rho-type GTPases from other organisms. The Candida albicans RHO1 gene could rescue a S. cerevisiae strain containing a rho1 deletion. Furthermore, recombinant Candida albicans Rho1p could reactivate the beta-1,3-glucan synthesis activities of both C. albicans and S. cerevisiae membranes in which endogenous Rho1p had been depleted by Tergitol NP-40-NaCl treatment. Candida albicans Rho1p was copurified with the beta-1,3-glucan synthase putative catalytic subunit, Candida albicans Gsc1p, by product entrapment. Candida albicans Rho1p was shown to interact directly with Candida albicans Gsc1p in a ligand overlay assay and a cross-linking study. These results indicate that Candida albicans Rho1p acts in the same manner as Saccharomyces cerevisiae Rho1p to regulate beta-1,3-glucan synthesis.

A case of large neonatal arteriovenous malformation with heart failure. Color Doppler sonography, MRI and MR angiography as early non-invasive diagnostic procedures.

We report a case of a large arteriovenous malformation (AVM) of neonatal onset with heart failure. Transfontanel color Doppler sonography revealed abnormal vessels in the early stage of the investigation. Magnetic resonance imaging (MRI) revealed numerous flow voids suggesting abnormal vessels, and magnetic resonance angiography (MRA) disclosed numerous bizarre abnormal vessels. Color Doppler sonography is a convenient and appropriate procedure for the early bedside diagnosis of neonatal AVMs. MRI and MRA can replace cerebral angiography for the diagnosis of neonatal AVMs.

A point mutation within each of two ATP-binding motifs inactivates the functions of elongation factor 3.

We have investigated how point mutations in the two ATP-binding motifs (G(463)PNGCGK(469)ST and G(701)PNGAGK(707)ST) of elongation factor 3 (EF-3) affect ribosome-activated ATPase activity of EF-3, polyphenylalanine synthesis, and growth of Saccharomyces cerevisiae. The point mutation impaired the ribosome-activated ATPase activity of EF-3, when glycine(463 and 701) and lysine(469 and 707) were replaced with valine and arginine, respectively. Thus, each glycine and lysine residue in both ATP-binding motifs is indispensable for EF-3's binding with ATP and the ensuing generation of ribosome-activated ATPase activity. Additionally, the mutant EF-3s did not catalyze polyphenylalanine synthesis in vitro when each glycine(463 and 701) was replaced with valine. The mutant EF-3s did not support cell growth in TEF3-disrupted S. cerevisiae, when each lysine(469 and 707) and glycine(463) was replaced with arginine and valine, respectively. Thus, each of the two ATP-binding motifs of EF-3 is indispensable for the ribosome-activated ATPase activity of EF-3, which is required for protein synthesis and cell growth in S. cerevisiae.

Characterization of the promoter region of a cell-adhesion protein gene derived from the basidiomycete Lentinus edodes.

An analysis of the 2 kb nucleotide sequence including the 5'-flanking region of a cell-adhesion protein-encoding gene (mfbA) isolated from the basidiomycete Lentinus edodes revealed that the promoter region contains a TATA box, a GC box, a CAAT box, a CT-rich sequence element, a TATA box, two CT-rich sequences, and a CAAT box, in the order, from upstream to downstream. Three major and three alternative transcriptional initiation sites were located 127, 129 and 131 nucleotides and 96, 193 and 197 nucleotides downstream from the downstream TATA box, and all the three major sites are positioned just in the most downstream CT-rich sequence. Three 16 bp unique sequences similar to the binding sites of Neurospora crassa transcriptional activator protein qa-1F (Baum et al. (1987) Expression of qa-1F activator protein: Identification of upstream binding sites in the qa gene cluster and localization of the DNA-binding domain. Mol. Cell. Biol. 7, 1256-1266) were present between the upstream TATA box and upstream CAAT box.

A fruiting body-specific cDNA, mfbAc, from the mushroom Lentinus edodes encodes a high-molecular-weight cell-adhesion protein containing an Arg-Gly-Asp motif.

A cDNA clone (designated mfbAc), encoding 2157 amino acids (aa), was isolated from a mature fruiting-body cDNA library of the edible mushroom Lentinus edodes. The mfbA transcript was abundant in mature fruiting bodies, detectable in immature fruiting bodies but absent in earlier developmental stages and in the vegetative mycelium. Although more abundant in the pileus than the stipe, only low levels were found in the gill tissue. The deduced MFBA protein (234.5 kDa) contained a cell-surface attachment-promoting Arg-Gly-Asp (RGD) motif. MFBA was produced in Escherichia coli using a maltose-binding protein (MBP) fusion vector, but it was cleaved into four fragments even in a protease-deficient host. A 425-aa MFBA peptide containing the RGD motif (named MFBA(582-1006) peptide) was successfully produced using the phage T7 expression system. This MFBA(582-1006) peptide exhibited a cell adhesion and spreading activity toward mammalian cells. This activity of the MFBA fragment was competitively inhibited by the Gly-Arg-Gly-Asp-Ser-Pro peptide but not by the Gly-Arg-Gly-Glu-Ser-Pro peptide, showing that the RGD motif of MFBA is essential for the cell-binding activity.

Recombinant chromosome 18 resulting from a maternal pericentric inversion.

We report on a newborn girl with duplication of 18q12.2-->18qter and deficiency of 18p11.2-->18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18)(p11.2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion.

Reverse flow in the intracranial arteries--the possible significance of comparative flow in the anterior cerebral and the basilar arteries.

Four infants with reverse flow patterns of the intracranial arteries are reported. Two with severe brain damage, had a reverse flow pattern in the anterior cerebral artery, which was recorded during the recovery stage from cardiac arrest. The other two patients showed a reverse flow pattern in the basilar artery and had a good prognosis. Reverse flow in the anterior cerebral artery suggests severe brain damage, but that in the basilar artery does not.

Cardio-facio-cutaneous (CFC) syndrome: report of two patients without hyperkeratotic skin lesions.

We report on two boys with the cardio-faciocutaneous (CFC) syndrome, but without hyperkeratotic skin involvement. They showed most of the manifestations of the CFC syndrome: growth and developmental retardation, relative macrocephaly, distinct facial appearance, sparse hair, and heart defects. Their skin was not hyperkeratotic, but patient 1 had mild atopic dermatitis and keloid-like depigmented spots.