An ultrastructural study of sex differentiation in the teleost Oryzias latipes.
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Age Factors↗
Biomedical subjects
N Satoh
Publications and source records attributed to N Satoh.
Sex differentiation of germ cells in the teleost, Oryzias latipes, during noraml embryonic development.
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Animals↗
A new and efficient method to generate human IgG monoclonal antibodies reactive to cancer cells using SCID-hu mice.
Human monoclonal antibodies (mAbs) are very useful for treatment of cancer, but they are difficult to obtain since immunization of humans is not a practical proposition at present. As an approach to circumvent this problem, we have simultaneously inoculated cancer tissues and regional lymph node cells obtained from lung cancer patients into SCID mice to allow in vivo stimulation of human lymphocytes against autologous cancer tissues. Human immunoglobulins, especially IgG, were observed in the SCID-hu sera, and some showed high reactivity to lung cancer cell lines. Testing of human B-lymphoblastoid cell lines obtained from SCID-hu spleen and thymus for antibody activity revealed 16-45% of them to be reactive to lung cancer cells. These percentages are high as compared with previous reports. Furthermore, we could establish 4 human IgG mAbs reactive to lung cancer cell lines. These results indicate successful stimulation of specific human lymphocytes in vivo, which thereby enables efficient generation of human monoclonal antibodies using SCID-hu mice.
Adenocarcinoma↗
Suppression of experimental autoimmune uveoretinitis by dietary calorie restriction.
To investigate the inhibitory effect of dietary calorie restriction on experimental autoimmune uveoretinitis (EAU) in rats, and its mechanism. Lewis rats were maintained on a 50% calorie-restricted diet for 2 months or 6 months. The control group was maintained on a 90% ad libitum intake for the same length of time. Experimental autoimmune uveoretinitis was elicited in both groups by immunization with an inter-photoreceptor retinoid-binding protein or its peptide. Rats in both groups were examined clinically, histopathologically, and immunologically. The severity of EAU was milder in the restricted diet group than in the control group. In EAU rats, production of interferon-gamma (IFN-gamma) in eyes and of IFN-gamma and tumor necrosis factor-alpha in draining lymph node cells was significantly lower in the restricted diet group than in the control group. Our results indicate that a calorie-restricted diet suppresses the development of EAU. The suppressed Th1-dependent immunological response is one of the reasons for the mildness of EAU in the calorie-restricted diet group of rats.
Animals↗
Fas expression and apoptosis in rats with experimental autoimmune uveoretinitis.
PURPOSE: To evaluate Fas expression on CD4 and CD8 T cells in each organ at each stage of experimental autoimmune uveoretinitis (EAU) and apoptotic cells within EAU eyes. METHODS: Rats were immunized with the uveitopathogenic peptide derived from interphotoreceptor retinoid-binding protein. Flow cytometry was performed in ocular cells, draining lymph nodes cells and splenic cells of EAU rats to investigate Fas expression by CD4 and CD8 lymphocytes. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining of apoptotic nuclei was performed on sections of EAU eyes. RESULTS: Fas expression by both ocular and splenic CD4 and CD8 lymphocytes was significantly higher than in lymph nodes at each stage. In EAU eyes, there was a relatively large population of lymphocytes with Fas expression (19.6-25.6% of CD4 and 33.2-53.4% of CD8). Apoptotic cells were more prominent in the EAU eyes with established disease than in those with early or resolving disease. CONCLUSIONS: These results suggest that the relatively large population of lymphocytes with Fas expression in EAU eyes reflects the activation of lymphocytes in these eyes, and that the increase in apoptotic inflammatory cells at the peak of established disease may participate in the spontaneous disappearance of EAU.
Animals↗
Uveitopathogenic site of the gamma-subunit of cyclic guanosine monophosphate phosphodiesterase in Lewis rats.
PURPOSE: The gamma-subunit of cyclic guanosine monophosphate phosphodiesterase (PDEgamma) plays an important role in the phototransduction process of rod photoreceptors. A previous report indicated that experimental autoimmune uveoretinitis (EAU) could be induced in Lewis rats by immunization with PDEgamma. In this study, we identified the uveitopathogenic site of PDEgamma synthetic peptides and identified pivotal amino acid residues using analogue peptides. METHODS: Several synthetic peptides derived from PDEgamma plus adjuvants were injected in Lewis rats. The induction of EAU was examined clinically and histologically. In addition, humoral and cellular immunity against peptides was investigated. RESULTS: The smallest uveitopathogenic peptide was identified as PDEgamma 64-76 (ITVICPWEAFNHL), which consists of 13 amino acid residues, and the core sequence was identified as PDEgamma 70-76 (WEAFNHL), which consists of 7 amino acid residues. The lowest dose of peptide to induce EAU was 0.03 nmol. The pivotal amino acid residues for eliciting EAU are at 70(W), 71(E), 73(F), and 75(H). CONCLUSION: Our findings demonstrated the presence of a potent uveitopathogenic site in PDEgamma whose potency in Lewis rats was comparable to that of interphotoreceptor retinoid-binding protein.
3',5'-Cyclic-GMP Phosphodiesterases↗
Two cases of malignant lymphoma complicated by hemophagocytosis resembling orbital cellulitis.
Two patients with malignant lymphoma complicated by hemophagocytic syndrome (HPS) are reported. Their clinical signs at onset were similar to those of orbital cellulitis. Lymphoma complicated by hemophagocytosis is called lymphoma-associated hemophagocytic syndrome (LAHS) and its prognosis is reported to be very poor. As far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. They died within 6 months after the first ophthalmological examination. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect HPS and should examine serum ferritin, which is a good marker of HPS. Early biopsy and consultation with a hematologist are very important.
Adolescent↗
Molecular studies of hemichordate development: a key to understanding the evolution of bilateral animals and chordates.
Using the Hawaiian acorn worm, Ptychodera flava, we began molecular studies on the development of hemichordates, a phylum previously unstudied at this level. Here we review results garnered from the examination of a few specific genes selected to help understand the evolution of vertebrate structures. These studies suggest new ideas about the evolution of developmental mechanisms in the deuterostomes. In a seminal observation, we noted an unexpected zone of expression of the Brachyurygene in the early anterior embryonic ectoderm where the mouth will form. Typically, the Brachyury gene is closely linked to development of the notochord and is expressed around the blastopore and in the posterior mesoderm in most animals. This first expression of Brachyury at the blastopore may represent a regulatory program associated with organizing the original animal head and gut opening, as suggested by the expression of Brachyury during hypostome formation in hydra. We believe that the anterior expression of Brachyury in deuterostomes represents the cooption of the program for organizing the original animal gut opening to form the deuterostome mouth. Recent data from the trochophore larva of a polychaete show that an anterior zone of expression of Brachyury is produced in this protostome by splitting of the Brachyury field during the formation of a gut with a mouth and anus by the lateral fusion of the sides of the blastopore. The ability to initiate independently a secondary regulatory program to organize the new mouth leading to an anterior field of Brachyury expression may be a signal event in the evolution of the deuterostomes. We also noted that the P. flava homolog of T-brain/Eomes, a gene closely related by sequence and expression around the blastopore to Brachyury and associated with development of the vertebrate brain, also exhibits early posterior expression around the blastopore and a field of de novo anterior ectoderm expression during later embryogenesis. The tissue in the zone of de novo anterior ectoderm expression of Pf-Tbrain produces the apical organ, a larval neural structure that has been touted as an evolutionary precursor of the chordate dorsal brain. The gene regulatory mechanisms responsible for initiating the anterior zone of de novo expression of T-brain may represent a cooption to specify early neuroectoderm of the regulatory program evolved first to drive anterior Brachyury expression for deuterostome mouth formation. It will be interesting to examine the possibilities that an ability to initiate the de novo anterior expression of the program that includes T-brain may be a key event in the evolution of the developmental mechanisms leading to the chordate dorsal nervous system.
Animals↗
Effect of zaprinast on nitric oxide levels in serum and aortic tissue.
Nitric oxide (NO), which is synthesized from the guanidino nitrogen of l-arginine by nitric oxide synthase (NOS), plays an important role in many physiological and pathological processes. Most of the effects of NO are mediated by cyclic guanosine 3'5 monophosphate (cGMP), which is synthesized by soluble guanylate cyclase (sGC) and degraded by phosphodiesterases (PDEs). Although the NO/cGMP pathway has been extensively studied, remarkably little is known about the regulation of NO release. Furthermore, controversial studies have indicated that intervention of the sGC/cGMP pathway modulates the release of NO. The purpose of this study was to evaluate the hypothesis that drugs that affect the sGC/cGMP pathway may modulate NO release and, if so, is there a correlation between NO levels and blood pressure effect? To this end, we investigated the effects of the PDE 5 inhibitor zaprinast on mean arterial pressure (MAP), nitrite/nitrate levels and cGMP in normotensive male Sprague Dawley rats. The results of the current study indicated that zaprinast dose-dependently increased plasma cGMP levels at 18, 24 and 36 mg/kg and decreased MAP at 24 and 36 mg/kg. However, zaprinast at 18, 24 and 36 mg/kg did not affect NO levels either in serum or aortic tissue. We have concluded that the PDE 5 inhibitor zaprinast has no regulatory effect on NO release in serum and aortic tissue, and NO was not involved in the hypotensive effect of zaprinast.
Animals↗
Phylogenetic position of the dicyemid mesozoa inferred from 18S rDNA sequences.
The dicyemid mesozoa, obligate symbionts in the cephalopod kidney, are simply organized multicellular animals. They have long been the subject of phylogenetic debates. Some authors have suggested that dicyemids represent an offshoot from an early metazoan ancestor. Other workers considered them to be degenerated progeny of higher metazoa, possibly parasitic trematodes. We determined the almost complete nucleotide sequences of 18S rDNA in two species of dicyemid, Dicyema orientale and Dicyema acuticephalum, isolated purely from cephalopod urine. We compared these sequences with sequences determined in the present study from three flatworm species, as well as with a variety of eukaryote sequences obtained from databases. The phylogenetic trees reconstructed with the use of the neighbor-joining, maximum-parsimony, and maximum-likelihood methods indicated that the dicyemids belong among the triploblastic animals (Bilateria). However, we cannot firmly establish the position of the dicyemids within the Bilateria because we cannot ignore the problem of long branch attraction between the myxozoans, dicyemids, nematodes, and acoel flatworms. The present results favor the hypothesis that the dicyemids do not represent an early divergent metazoan group, but rather a group degenerated from a triploblastic ancestor.
Animals↗
Growth inhibition of human osteosarcoma HuO9 cells by methylglyoxal bis(cyclopentylamidinohydrazone) in vitro and in vivo.
Polyamines are considered to be important intracellular molecules for the proliferation of cancer cells. In this study, effects of methyl-glyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a potent inhibitor of the polyamine biosynthetic pathway, on the growth of human osteosarcoma HuO9 cells have been investigated. MGBCP dose-dependently inhibited the growth of HuO9 cells, in which the contents of spermine, spermidine and putrescine decreased concomitantly. The MGBCP-treated cells clearly exhibited morphological changes, indicating the blebbing and chromatin condensation which are characteristic of apoptosis. Characteristic oligonucleosomal-sized DNA fragments were observed in the MGBCP-treated cells. In in vivo experiments MGBCP (20 or 50 mg/kg) inhibited the growth of transplanted HuO9 tumors in mice. These findings suggest that the inhibition of polyamine synthesis results in the suppression of growth of osteosarcoma HuO9 cells, eventually inducing apoptosis in these human osteosarcoma cells in vitro and in vivo.
Animals↗
Successful surgical treatment of pulmonary artery sling and partial anomalous pulmonary venous drainage in an infant.
A 8 month old infant with pulmonary artery sling and partial anomalous pulmonary venous drainage was reported. The patient was seen initially with severe stridor. Diagnosis was made by barium swallow study, echocardiography, bronchoscopy, and pulmonary arteriography. The patient was operated on through a median sternotomy; the left pulmonary artery was dissected deep between the trachea and esophagus, and then reimplanted to the side of the main pulmonary artery. Systemic heparinization and microsurgical technique were used. Simultaneous intracardiac repair was carried out by means of extracorporeal circulation. The patient improved dramatically after operation. Postoperative pulmonary arteriogram revealed a wide patent left pulmonary artery, and postoperative perfusion lung scan confirmed improved perfusion of the left lung. It is concluded that pulmonary artery sling should be treated surgically as soon as diagnosed. From the surgical point of view, the left pulmonary artery should be anastomosed to the main pulmonary artery with micro-surgical technique to avoid late occlusion of the left pulmonary artery.
Abnormalities, Multiple↗
Induction of apoptotic cell death in three human osteosarcoma cell lines by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP).
Our previous experiments have shown that methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine synthesis inhibitor, suppresses the growth of osteosarcoma cells repressing their intracellular polyamine levels, and that this inhibition of cell growth is only partially reversed by the addition of polyamines. In the present study, we found evidence indicating that the incomplete recovery of cell growth by the addition of polyamines to the polyamine-depleted cells was due to programmed cell death (apoptosis) induced by MGBCP. Morphological changes showing blebbing and chromatin condensation were observed in MGBCP-treated cells, and hypodiploid subpopulations containing apoptotic cells were clearly visible in the profile of flow cytometric analysis. Characteristic oligonucleosomal-sized fragments were increased as the concentration of MGBCP was increased. The results presented here suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in three human osteosarcoma cell lines.
Apoptosis↗