Epicardium is required for sarcomeric maturation and cardiomyocyte growth in the ventricular compact layer mediated by transforming growth factor β and fibroblast growth factor before the onset of coronary circulation

The epicardium, which is derived from the proepicardial organ (PE) as the third epithelial layer of the developing heart, is crucial for ventricular morphogenesis. An epicardial deficiency leads to a thin compact layer for the developing ventricle; however, the mechanisms leading to the impaired development of the compact layer are not well understood. Using chick embryonic hearts, we produced epicardium‐deficient hearts by surgical ablation or blockade of the migration of PE and examined the mechanisms underlying a thin compact myocardium. Sarcomeric maturation (distance between Z‐lines) and cardiomyocyte growth (size) were affected in the thin compact myocardium of epicardium‐deficient ventricles, in which the amounts of phospho‐smad2 and phospho‐ERK as well as expression of transforming growth factor (TGF)β2 and fibroblast growth factor (FGF)2 were reduced. TGFβ and FGF were required for the maturation of sarcomeres and growth of cardiomyocytes in cultured ventricles. In ovo co‐transfection of dominant negative (dN)‐Alk5 (dN‐TGFβ receptor I) and dN‐FGF receptor 1 to ventricles caused a thin compact myocardium. Our results suggest that immature sarcomeres and small cardiomyocytes are the causative architectures of an epicardium‐deficient thin compact layer and also that epicardium‐dependent signaling mediated by TGFβ and FGF plays a role in the development of the ventricular compact layer before the onset of coronary circulation.     

Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis

BackgroundPsoriasis is a common chronic inflammatory skin disorder with a high prevalence (3–5%) in the Caucasian population. Although the number of capillary vessels increases in psoriatic lesions, there have been few reports that have specifically examined the role of angiogenesis in psoriasis. Angiogenic factors, such as vascular endothelial growth factor (VEGF), may dominate the activity of anti-angiogenic factors and accelerate angiogenesis in psoriatic skin.ObjectiveWe investigated to identify small peptide mimetics of PEDF that might show anti-angiogenic potential for the topical treatment for psoriasis.MethodsWe examined the expression of PEDF in skin by immunohistochemical staining, immunoblotting, and RT-PCR. To identify potential PEDF peptides, we screened peptides derived from the proteolytic fragmentation of PEDF for their anti-proliferative action. Anti-psoriatic functions of these peptides were analyzed using a mouse graft model of psoriasis.ResultsThe specific low-molecular weight peptides (MW < 850 Da) penetrated the skin and showed significant anti-angiogenic activity in vitro. Topical application of these peptides in a severe combined immunodeficient mouse model of psoriatic disease led to reduced angiogenesis and epidermal thickness.ConclusionsThese data suggest that low-molecular PEDF peptides with anti-angiogenic activity may be a novel therapeutic strategy for psoriasis.     

A case of uterine endometritis caused by Atopobium vaginae

Although Atopobium vaginae has been reported as a causative organisms in patients with bacterial vaginosis and/or tubo-ovarian abscess, clinical significance of Atopobium species has not been defined to date. Here we report the case of uterine endometritis caused by A. vaginae.     

Immunohistochemical study of the fourth cell type in the olfactory epithelium in guinea pigs and in a patient.

The mammalian olfactory epithelium consists of supporting cells, olfactory receptor cells, basal cells and a fourth cell type, which has recently been discovered. In this study we examine this fourth cell type using immunohistochemical techniques. Anti-Purkinje-specific spot-35 protein (S-35), anti-S-100 protein (S-100), anti-neuron-specific enolase (NSE), antichromogranin A and antisynaptophysin antisera were used for the immunostaining. The fourth cell type immunoreacted only to anti-S-35 antiserum and did not react to other antisera in guinea pigs. On the other hand, in the human S-100 immunoreactivity was seen in the fourth cell type as well as weak reactivity to S-35. NSE immunoreactivity was found only in the olfactory receptor cells of guinea pigs and the human. From these results it is assumed that this fourth cell type is a second chemoreceptor different from the olfactory receptor cells because S-35 and S-100 are Ca(++)-binding proteins.     

Epidemiologic Survey of Children with End-Stage Renal Disease

We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end-stage renal disease (ESRD). Sixty-nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow-up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.     

Spatial localization of colour and luminance stimuli in human peripheral vision

A variety of studies suggest the localization of objects in three-dimensional space is predominantly the task of the magnocellular (M) system, and conversely that the parvocellular (P) system plays little or no role in localization. However, there are conflicting reports and the goal of this paper was to determine whether spatial localization is predominantly accomplished by one or the other visual system. Both manual pointing and three-target alignment protocols were used to measure localization accuracy for eccentrically presented patches of a sinewave grating. Two general approaches were adopted to activate preferentially one or the other pathway: (1) we varied the spatio-temporal frequency, contrast and chromatic properties of the stimulus to conform with the physiological response properties of either M or P cells; and (2) some measurements were made both with steady fixation and during large saccades, as the latter have been reported to cause selective suppression of the M system [Burr, Morrone & Ross (1994). Nature, 371, 511-513]. Each stimulus was presented at or near its detection contrast threshold, which was determined separately for each visual field location using forced-choice procedures. Using manual pointing, both M- and P-type stimuli were localized to within about 1.3 degrees at retinal eccentricities near 10 degrees. This accuracy was not affected by distractor targets in the peripheral field or temporal uncertainty in stimulus presentation, but was reduced by a similar amount for each stimulus type during saccadic eye movements. Using the alignment task, localization accuracy remained at about 1.3 degrees for P-type stimuli but improved to 0.5 degrees for M-type stimuli. We conclude that both M and P systems play an equally important role in localizing peripheral targets for the purpose of visuo-motor tasks such as pointing, but that the M system may offer an advantage over the P system for the perceptual task of localizing a stimulus relative to nearby targets.     

A novel antitumor compound,NC-190, induces topoisomerase II-dependent DNA cleavage and DNA fragmentation

 A novel benzophenazine derivative, NC-190, is a potent antitumor compound. NC-190 has been shown to inhibit the DNA strand-passing activity of DNA topoisomerase II. We investigated further the mode of action of NC-190 against DNA topoisomerase II and DNA fragmentation. NC-190 inhibited the decatenation activity of purified topoisomerase II, but had only a weak inhibitory effect against topoisomerase I. A topoisomerase II-dependent DNA cleavage assay showed that NC-190 inhibited the enzyme activity by stabilizing a topoisomerase II–DNA cleavable complex. NC-190 induced growth inhibition, protein-linked DNA breaks, and DNA fragmentation in cultured HL-60 cells in a dose-dependent manner. These activities of NC-190 in HL-60 cells were comparable to those of etoposide (VP-16). These results demonstrate a good correlation among growth inhibition, topoisomerase II-dependent DNA cleavage, and DNA fragmentation induced by NC-190. A DNA unwinding assay showed that NC-190 had intercalating activity, but its activity appeared to be weaker than those of ethidium bromide and adriamycin. These results indicate that the mechanism by which NC-190 exhibits antitumor activity may be the inhibition of topoisomerase II. Received: 23 September 1994/Accepted: 2 August 1995     

Manifestation of Bilateral Huge Ovarian Metastases from Colon Cancer Immediately After the Initial Operation: Report of a Case

This report describes the case of a 34-year-old premenopausal woman in whom bilateral huge ovarian metastases were found immediately after initial surgery for sigmoid colon cancer. Both ovaries had been intact at the time of sigmoidectomy, but 2 months later, she complained of persistent vaginal bleeding, and large bilateral metastases were detected in both ovaries. Oophorectomy with intraperitoneal chemotherapy proved ineffective and the patient died 3 months later, after a second operation, from peritoneal dissemination. This case report serves to demonstrate the importance of searching for synchronous or nonsynchronous metastases to the ovaries after surgery for colon cancer in young women. Consideration should also be given to the feasibility of performing prophylactic oophorectomy or administering intensive chemotherapy in association with colon resections for carcinoma for premenopausal women because of the ineffectiveness of these modalities as treatment for metastatic disease. Received: February 6, 2001 / Accepted: September 11, 2001