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Biomedical subjects

C Mori

Publications and source records attributed to C Mori.

At least 19 recordsLinked to original sources

Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells. The genes for HGF/SF and its receptor (the c-met proto-oncogene product) are expressed in many tissues during the embryonic periods and in the adult. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development. To examine the physiological role of HGF/SF, we generated mutant mice with a targeted disruption of the HGF/SF gene. Here we report that homozygous mutant embryos have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis.

Allantois

Tissue accumulation of sulfatide and GM3 ganglioside in a patient with variant Farber disease.

We analyzed the lipids in the tissues of a patient with an atypical form of Farber disease who developed several clinical symptoms not seen in patients with typical Farber disease (acid ceramidase deficiency). Lipids were extracted from formalin-fixed brain, liver and kidney and purified by ion exchange and silica gel column chromatographies and further by high-performance liquid chromatography on a silica gel column. We performed structural and quantitative analyses of three lipids named lipids X, Y and Z. Lipid X accumulated in the liver but not in the brain. Accumulation of lipids Y and Z was observed in liver and kidney. The content of lipid Y in the patients liver was more than ten times that in a control. The structures of lipids X, Y and Z were confirmed by means of 1H-nuclear magnetic resonance spectroscopy, fast atom bombardment mass spectrometry, infrared absorption spectroscopy, and component analysis involving gas liquid chromatography and gas chromatography-mass spectrometry. The structures of lipids X, Y and Z were identified as those of ceramide, sulfatide and GM3 ganglioside, respectively. These results suggest two possibilities. One is that the accumulation of glycolipids such as sulfatide and GM3 ganglioside is a secondary event produced by the accumulation of ceramide due to ceramidase deficiency. The other is that the accumulation of glycolipids other than ceramide is due to a deficiency of sphingolipid activator proteins which may affect the degradation of sulfatide and GM3 ganglioside as well as ceramide.

Acid Ceramidase

Programmed cell death in the interdigital tissue of the fetal mouse limb is apoptosis with DNA fragmentation.

BACKGROUND: Programmed cell death is an essential event during mammalian morphogenesis which eliminates unnecessary cells to accomplish histogenesis and organogenesis. Cell death in interdigital spaces of the developing limb is a classical example of morphogenetic cell death. We investigated whether classical programmed cell death in the interdigital tissue of the developing limb in mice is apoptosis with fragmentation of nuclear DNA and also examined sequentially the occurrence of programmed cell death and cell proliferation in the developing limb of mouse fetuses to analyze their interrelation. METHODS: We examined the occurrence of apoptotic cell death in the developing limbs of mouse fetuses by using Nile blue sulphate staining, agarose gel electrophoresis for detecting DNA laddering, and a cytochemical labeling of DNA fragmentation. We also labeled proliferating cells using BrdU/anti-BrdU immunohistochemistry and examined the interrelation between apoptotic programmed cell death and cell proliferation. RESULTS: DNA ladders, a biochemical evidence of apoptosis, were detected in DNA extracts from the interdigital tissue of day 13 mouse fetuses by agarose gel electrophoresis. Programmed cell death and DNA fragmentation were detected by Nile blue staining and cytochemical labeling of DNA fragmentation, respectively, in the interdigital mesoderm and in the regions of presumptive joints of the digit. BrdU/anti-BrdU immunohistochemistry for identifying proliferating S-phase cells revealed that interdigital mesenchymal cells cease DNA synthesis before programmed cell death and DNA fragmentation begin. CONCLUSIONS: We confirmed that both cytological apoptotic alterations and fragmentation of nuclear DNA occur in the interdigital tissue and presumptive joint areas of fetal mouse limbs, and they appear to play a significant role in the separation of digits as well as the formation of joint cavities.

Animals

Characterization of Fsc1 cDNA for a mouse sperm fibrous sheath component.

The fibrous sheath is a major cytoskeletal structure in the principal piece of the mammalian sperm flagellum. We have cloned a cDNA and used it to characterize the expression of mRNA for a mouse sperm fibrous sheath protein. Peptides from a tryptic digest of fibrous sheath proteins were separated by HPLC and a 31 amino acid sequence was obtained from one of the peptides. Through the use of degenerate oligonucleotide polymerase chain reaction (PCR) primers predicted from this sequence, an 80-bp product was amplified from mouse testis first-strand cDNA. This was utilized as a probe to isolate a 2.9-kb cDNA clone from a mouse round spermatid cDNA library. Sequence analysis of the cDNA clone showed that it encodes a protein with an open reading frame of 849 amino acids and includes the original peptide sequence. The predicted protein has a molecular weight of 93,795 and contains 32 cysteine residues and 32 potential phosphorylation sites. It has no significant homology with other known cytoskeletal proteins. Northern blot analysis detected an mRNA of approximately 3 kb that was abundant in round spermatids of the mouse and in testes from six other mammalian species, but not in twelve somatic tissues from the mouse. In situ hybridization analysis indicated that the mRNA is first detected in step 1-6 spermatids, is most abundant in step 8-12 spermatids, and decreases in amount in step 13-15 spermatids, suggesting that expression of the mRNA occurs in the postmeiotic phase of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Disruption of the mouse RBP-J kappa gene results in early embryonic death.

The RBP-J kappa protein is a transcription factor that recognizes the sequence C(T)GTGGGGA. The RBP-J kappa gene is highly conserved in a wide variety of species and the Drosophila homologue has been shown to be identical to Suppressor of Hairless [Su(H)] which plays important roles in the development of the peripheral nervous system. To explore the function of the RBP-J kappa gene in mouse embryogenesis, a mutation was introduced into the functional RBP-J kappa gene in embryonic stem (ES) cells by homologous recombination. Null mutant ES cells survived but null mutant mice showed embryonic lethality before 10.5 days of gestation. The mutant mice showed severe growth retardation as early as 8.5 days of gestation. Developmental abnormalities, including incomplete turning of the body axis, microencephaly, abnormal placental development, anterior neuropore opening and defective somitogenesis, were observed in the mutant mice at 9.5 days of gestation. RBP-J kappa mutant embryos expressed a posterior mesodermal marker FGFR1. Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-J kappa gene was revealed to be essential for postimplantation development of mice.

Animals

Synthesis of some 4H-pyrido[1,2-a]pyrimidin-4-ones investigated as antimicrobial agents.

Synthesis of some 4H-pyrido[1,2-a]pyrimidin-4-ones and assay of their antibacterial and antifungal activity are reported. Compounds 3a-e,g were prepared by reaction of substituted 2-chloromethyl-4H-pyrido[1,2-a]pyrimidin-4-ones 2a-c with suitable amines. These compounds and the previously obtained analogues 5a-o and 6a,b have been tested for their antimicrobial activity. All tested compounds were devoid of antimicrobial activity.

Anti-Bacterial Agents

Sexing of human embryos and fetuses by fluorescent in situ hybridization (FISH) to paraffin-embedded tissues with sex chromosome-specific DNA probes.

A fluorescent in situ hybridization (FISH) study was carried out on paraffin sections of human embryonic and fetal tissues with two DNA probes, DXZ1 and DYZ1 (Oncor), for X and Y chromosome-specific DNA sequences, respectively. The specificity of the DNA probes was confirmed on metaphase and interphase lymphocytes of healthy normal adult males. The paraffin blocks of the human embryonic and fetal tissues examined in the present study had been stored at room temperature for up to 5 years after fixation in 4% paraformaldehyde. All the seven embryos and five fetuses examined were successfully sexed by FISH. The cells from three embryos and four fetuses were positive for a hybridization signal with each of the DXZ1 and DYZ1 probes and they were classified as male. The cells from the remaining four embryos and one fetus were positive for two identical hybridization signals with the DXZ1 probe in a nucleus instead of the absence of the signal hybridized with DYZ1, indicating that their cells have two X chromosomes but no Y chromosomes. The FISH results for the five fetuses examined were consistent with their genital sex and/or gonadal histology. The FISH results were highly specific and no false positive or false negative results were obtained. Thus, the FISH technique has been shown to visualize specific DNAs in situ on paraffin sections and to be useful to determine the sex of fixed embryos and fetuses retrospectively.

Cells, Cultured

Highly sensitive detection of viral RNA genomes in blood specimens by an optimized reverse transcription-polymerase chain reaction.

A protocol was developed for a highly sensitive detection of viral RNA in blood specimens by reverse transcription coupled with a nested polymerase chain reaction. Using Japanese encephalitis virus (JEV) as a model, the optimized reverse transcription-polymerase chain reaction (ORTPCR) detects as few as 3-5 virions in 0.1 ml of whole blood specimens. The effectiveness of this assay system is confirmed by diagnosis of human hepatitis C viral (HCV) infection.

Animals

Cytochemical identification of programmed cell death in the fusing fetal mouse palate by specific labelling of DNA fragmentation.

The process of palate fusion was examined in 13- and 14-day-old mouse fetuses by using in situ staining for nuclear DNA fragmentation (TUNEL method) and immunofluorescent staining for keratin, with special reference to the disruption of the midline epithelial seam. TUNEL-positive cells were found in the disappearing midline seam and the oral and nasal epithelial triangles at some late stages of palate fusion, but not in the palatal shelves prior to contact or in the intact midline epithelial seam. It seems that DNA fragmentation or apoptosis is required for the midline epithelial seam to disrupt, but may not be necessary for initial contact of palatal shelves or for the epithelial fusion of opposing palatal shelves. A similar sign of apoptotic cell death was observed in the disappearing epithelial seam between the fusing nasal septum and dorsal palate. We have demonstrated that apoptotic programmed cell death does occur at some stages of palate fusion, although the present results do not exclude the possibility of epithelial-mesenchymal transformation and the oral and nasal migration of midline epithelial cells.

Animals

The effect of bunazosin on monocrotaline-induced pulmonary hypertension in rats.

In order to estimate the long-term hemodynamic and histologic effects of bunazosin hydrochloride on primary pulmonary hypertension (PPH), for which effective internal therapy has not yet been proposed, we produced subacute pulmonary hypertension in 6 week old Sprague-Dawley rats by injecting one dose of monocrotaline. Bunazosin (10 mg/kg) was administered intraperitoneally every day and bodyweight and hemodynamic parameters were measured. Right ventricle (RV) and left ventricle with septum (LV +S) were weight separately. Medial thickness of the small pulmonary artery was calculated. In the bunazosin group, the increase of right ventricular systolic pressure (RVSP) as pulmonary arterial systolic pressure and the ratio of RVSP to pulmonary flow were limited, without causing systemic hypotension, compared to the control group. Weight ratio of RV/(LV +S) had a tendency to be limited in the bunazosin group. As for medial thickness, there was no significant difference between the two groups. It may be concluded that bunazosin hydrochloride should be considered for clinical trials in treatment of PPH in humans.

Adrenergic alpha-Antagonists

Change in the hospital setting: adopting a team approach for nonorganic failure-to-thrive.

The change process is described for the adoption of a multidisciplinary team approach to nonorganic failure-to-thrive (NOFTT) management at a pediatric care facility. A member of the nursing staff acted as a change agent. The need for change was documented with medical record audits. A team was developed and a management protocol derived from an external evaluation of successful programs described in the literature. Preliminary outcomes of the project are reported. Box 1 at the end of this article contains criteria for NOFTT diagnosis and an outline of the team's protocol.

Child

[Perceived health of persons and their practice of health promoting activities].

The perceived health of persons and their practice of health promoting activities were surveyed using a self-rating questionnaire with 49 items assessing level of health, practice of health promoting activities, life styles, health education, and participation in health screening for general health conditions and cancers. The questionnaires were mailed to 2,500 residents of a city, aged from 30 to 69 years old, randomly selected according to the composition ratios of the populations in the city. Persons from 2,333 subjects (1,057 male and 1,276 female) were effectively collected, representing about 1% of the city's population. General health was good in about 85% of the subjects, with decreases observed with age. Practice of activities for health promotion was wide-spread among the subjects. These activities included regularity, diet, nutrition, smoking and drinking control, physical exercise, sleep, and rest. The subjects expressed strong fear of cancers and concerns about deterioration in physical fitness. Their target life style was one with adequate sleep and rest, regularity in eating, good nutrition, and avoidance of overwork. Health screening participation rates were low at approximately 28% because of their perceived good health, and busy daily life and work. It appears that the perceived health of citizens may not always correlated with the practice of health promoting activities.

Adult

Histopathologic and coronary angiographic assessment of effectiveness of aspirin or aspirin-and-gammaglobulin in Kawasaki disease.

Coronary angiography and right ventricular endomyocardial biopsy were performed in 36 children during convalescence (days of illness 23-86; mean = 41.5 days) following acute Kawasaki disease. Treatment of the acute stage was not randomized; it consisted of aspirin alone in 14 subjects (during the years 1980-88), and gammaglobulin and aspirin in 22 subjects (1984-91). The dosage of aspirin was 30 mg/kg orally during the acute febrile stage and 5-10 mg/kg orally after lysis of fever. The dosage of gammaglobulin was 200 mg/kg x 5 days in 19 patients, 200 mg/kg x 3 days in one patient, 200 mg/kg x 1 day + 400 mg/kg x 4 days in one patient and 200 mg/kg x 4 days + 400 mg/kg x 4 days in one patient. Among the 14 patients treated with aspirin alone, large coronary aneurysms were noted in four, moderate aneurysms in three and transient aneurysms in one. Among 22 patients treated with gammaglobulin, only five had aneurysms and these were transient. The histopathological (HP) score based on myocardial disarrangement, degeneration and hypertrophy; interstitial edema, large mononuclear cell infiltration and fibrosis; and endocardial abnormalities was higher in the aspirin group than in gammaglobulin group. Moderate to severe HP changes were noted in five subjects in the aspirin group, while moderate HP changes were found in only two subjects in the gammaglobulin group. Gammaglobulin therapy not only reduced the incidence of the coronary arterial lesions but also reduced the severity of myocardial damage from moderate or severe to mild in Kawasaki disease.

Acute Disease

Expression of epidermal growth factor receptor after partial pancreatectomy in adult rats: an immunohistochemical study.

The expression and localization of epidermal growth factor (EGF) were investigated immunohistochemically using an anti-EGF receptor antibody in the pancreas of partial pancreatectomized and sham-operated adult rats. In the sham-operated pancreas, immunoreactive products against EGF receptor were only slightly positive in the pancreatic acinar cells. In the partial pancreatectomized pancreas on the fifth day after operation, EGF receptor immunoreactivity was intensely positive in the acinar cells, in some cells lining the intercalated ducts and some basal cells of the acinus, but it was not detected in the pancreas when exogenous EGF was given to the rat after partial pancreatectomy for three days. The present results suggest that EGF receptor is expressed in the regenerating pancreatic tissue, and EGF could be involved in the mechanism of pancreatic regeneration in rats.

Animals

Immunohistochemical study on epidermal growth factor (EGF) receptor during carcinogenesis in the rat liver.

The expression and localization of epidermal growth factor (EGF) receptor were investigated immunohistochemically using anti-EGF receptor antibody in the normal rat liver and 3'-methyl-4-dimethylaminoazobenzen (3'-Me-DAB) induced tumors in rats. In 8 weeks after 3'-Me-DAB treatment, multiple nodules of cholangiocarcinoma were found in the rat liver, and atypical nodules of hepatocytes were also found 14 weeks later. Immunoreactive products against EGF receptor were only slightly positive in the normal liver, the nodule of cholangiocarcinoma, and atypical nodule of hepatocytes. It was noted that EGF receptor immunoreactivity was more intense in non-cancerous tissue adjacent to tumorous nodules than in the cancerous tissue. The present finding suggests that the expression of EGF receptor may be associated with regenerating as well as carcinogenetic processes in the rat liver.

Adenoma, Bile Duct