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Biomedical subjects

K Shiota

Publications and source records attributed to K Shiota.

At least 55 records · Page 3Linked to original sources
PubMed2000

Immunohistochemical analysis of apoptosis-related proteins in human embryonic and fetal pancreatic tissues.

BACKGROUND: The growth of both cancer cells and fetal tissue is rapid; however, cancer cells de-differentiate and proliferate in a disorderly manner, whereas fetal tissues differentiate and proliferate in an orderly manner. Thus, there may be both common and different factors that are involved in the process of the uncontrolled cell growth of pancreatic cancers and the development of the fetal pancreas. The common part of the mechanisms should be in the regulation of the cell cycle, resulting in rapid proliferation via such mechanisms as growth stimulation and avoidance of apoptosis. Therefore, in the current study we investigated the expression of apoptosis-related proteins in fetal pancreatic tissues. METHODS: Sixteen human embryonic and fetal pancreatic tissues obtained between 6 and 32 wk of gestation were used. We immunohistochemically examined the protein expression of Bcl-2, Bcl-XL, Mcl-1, and Bax. Further, the expression of insulin, glucagon, and proliferting cell nuclear antigen (PCNA), and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining were examined. RESULTS: In embryonic and fetal pancreatic tissues, Bcl-2 was not detected in any type of pancreatic cell (acinar, ductal, or islet). Bcl-XL was expressed in all types of pancreatic cells throughout the gestation. Mcl-1 was expressed in all types of pancreatic components, and strongly expressed in the margin of the islets. Bax, a pro-apoptotic protein, was expressed in all components. PCNA was strongly expressed in the embryonic and fetal pancreas, especially in early stages of gestation; however, TUNEL staining was negative in all samples. At least one antiapoptotic protein was expressed in all types of pancreatic cells. CONCLUSION: The results of the current study indicate that active proliferation and avoidance of apoptosis take place in embryonic and fetal pancreatic tissues, which may be controlled by particular combinations of apoptosis-related proteins. Among these proteins, Bcl-XL and Mcl-1 may play an important role in the proliferation and differentiation of the embryonic and fetal pancreas.

Apoptosis↗
PubMed2000

Clinicopathologic study on hepatocellular carcinoma negative for hepatitis B surface antigen and antibody to hepatitis C virus.

Among 326 consecutively resected cases of hepatocellular carcinoma (HCC), we studied clinicopathologic features of 13 cases (NBNC-HCC) negative for hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), antibody to hepatitis B core antigen (HBcAb), hepatitis B envelope antigen (HBeAg), antibody to HBeAg (HBeAb), and antibody to hepatitis C virus (HCVAb). Forty-four HCC cases positive only for HBsAg (B-HCC) and 232 cases positive only for HCVAb (C-HCC) were studied as controls. Clinically, NBNC-HCC cases showed good liver function reserve. None of NBNC-HCC cases had periodic medical check ups and HCC was detected in 12 cases (92.3%) incidentally. Pathologically, the mean tumor diameter was significantly larger and the histologic grade was less differentiated in NBNC-HCC cases than in B-HCC and C-HCC cases. In the background liver, liver cirrhosis was associated in 15.4% of NBNC-HCC cases, 50.0% of B-HCC and 38.2% of C-HCC cases. The degree of inflammation and fibrosis was less in NBNC-HCC cases, and two cases (15.4%) had almost normal liver histology. In NBNC-HCC cases, synchronous and metachronous multicentric occurrence was not observed. In B-HCC cases, synchronous multicentric occurrence was found in 1 case (20.0%), but no metachronous multicentric occurrence. In C-HCC cases, synchronous and metachronous multicentric occurrence was found in 13 (43.3%) and 8 (30.8%) cases, respectively. However, the cumulative recurrence-free rate was not significantly different among the three groups. Accordingly, it was suggested that better prognosis could be expected in NBNC-HCC cases compared with B- and C-HCC cases, if the cancer could be detected in the early stage.

Aged↗
PubMed2000

[Simultaneous operation for lung tumor and cardiovascular disease].

Successful simultaneous operation for lung tumor and cardiovascular disease was performed in three cases. A 76-year-old man with stage I lung cancer and ischemic heart disease underwent a partial lobectomy following single coronary artery bypass grafting through a median sternotomy. A 62-year-old man with stage I suspected lung cancer and thoracic aortic aneurysm underwent a partial segmentectomy before aneurysmectomy and patch closure using vascular prosthesis through a left posterolateral thoracotomy. These two cases were performed under extracorporeal circulation. A 69-year-old man with bronchogenic carcinoma and abdominal aortic aneurysm underwent a left upper lobectomy with standard lympho node dissection following aneurysmectomy and grafting using vascular prosthesis. As a simultaneous procedure, limited operation for lung tumor, especially for stage I non-small cell lung cancer, is acceptable for cases in using extracorporeal circulation. On the other hand, except emergency ruptured cases of abdominal aortic aneurysm, standard radical operation for lung cancer as a simultaneous procedure is preferred for cases such as lung cancer accompanied with abdominal aortic aneurysm without extracorporeal circulation.

Aged↗
PubMed2000

Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout mice.

While the targeted disruption of a gene is a powerful tool for investigating the physiological functions of that gene, disruption of a gene essential for embryogenesis leads to embryonic death. Rescue of the defect(s) causing embryonic death should promote survival, thus permitting further evaluation of the roles that the gene plays later in the developmental process. Disruption of the gene for mouse hepatocyte growth factor/scatter factor (HGF/SF) leads to middle-stage embryonic lethality because of a defect in placental development. Here we report that a single injection of HGF/SF at embryonic day 9.5 (E9.5) into the amniotic cavity of HGF/SF(-/-) embryos rescued the placental defect and resulted in the survival of the embryos until term. Histological analysis suggested that HGF/SF is also required at the late stage of development for tissue organogenesis. Thus, injection of a secreted factor can be a useful method to rescue the defects causing embryonic lethality.

Amniotic Fluid↗
PubMed2000

Time-lapse observation of branching morphogenesis of the lung bud epithelium in mesenchyme-free culture and its relationship with the localization of actin filaments.

It has been shown that branching morphogenesis of the lung bud is mediated by epithelial-mesenchymal interaction via such molecules as FGF10, BMP4 and Shh. However, a recent study showed that the isolated lung epithelium still undergoes branching morphogenesis in vitro even in the absence of mesenchyme (Nogawa and Ito, 1995). In the present study, we observed in vitro the dynamic movement of the isolated lung epithelium of the fetal mouse using time-lapse recording, and investigatedthe roles of actinfilaments in branching of the lung bud. First, time-lapse observation of the initial phase of lung branching morphogenesis revealed that at the sites of cleft formation, the epithelial surface was retracted inward from its original position. From this observation we assumed that there should be some structures which exert a physical force on the epithelium, and the localization and arrangement of actin fibers in the cultured lung epithelium were examined at various stages of branching morphogenesis. At the prebudding (6 h) and onset-budding (24 h) stages, no specific localization of actin filaments was observed in the lung bud epithelium, but at the postbudding stage (48 h) they were localized densely in the cells at the tip of the branched lung epithelium. The cell density was not different between the tip and cleft regions of the lung bud epithelium. When cultured with FGF-soaked beads, an actin-rich region was induced at the tip of the lung bud which was growing toward an FGF-soaked bead. These results indicate that actin fibers do not play a significant part in cleft formation but can be secondarily induced by FGF in the surrounding matrix and play some roles at later shaping of the branch in lung morphogenesis.

Actins↗
PubMed1999

Caudal dysgenesis in staged human embryos: Carnegie stages 16-23.

The severity of expression of malformations of the median axis in the caudal region of human embryos is highly variable and ranges from caudal dysgenesis and sirenomelia to simple sacral hypoplasia. Several forms of sacral dysgenesis may be discovered later in life. This shows that caudal malformations of relatively lesser severity should occur at a greater frequency than actually reported. In the present study we looked at the morphology and histology of some human embryos with caudal dysgenesis. Several developmental alterations of the median axis were observed. These included significant reduction in the craniofacial mesenchyme characterized by hypoplasia of the pharyngeal arches, palatal shelves, and agenesis or hypoplasia of the auricular hillocks at the rostral end, absence of the caudal trunk from midsacral to all coccygeal segments, vertebral fusion or agenesis, defective development of the primary and secondary neural tubes, rectal and urinary tract dysgenesis, and deficiency, malrotation, and deficiency of the limbs at the caudal end. Hindlimb malformations included bilateral agenesis (one case), meromelia, and various forms of abnormal rotation, but no instances of sirenomelia were present. Radial dysgenesis has been reported to be associated with caudal dyplasia in the literature, however, we observed agenesis of the ulna in one and of the fibula in another embryo. There was an impressive association between limb malformations and body wall defects. The histological studies demonstrated caudal vascular deficiency and hemorrhagic lesions in the limbs of the dysplastic embryos. The data suggest that these polytopic field defects arise very early in development possibly as result of disturbances to fundamental developmental events that share common molecular and cellular mechanisms.

Abnormalities, Multiple↗
PubMed1999

Involvement of germ cell apoptosis in the induction of testicular toxicity following hydroxyurea treatment.

The present study investigated the occurrence of apoptotic cell death in the mouse testis at various intervals following the administration of hydroxyurea (HU). The presence of apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and by DNA fragmentation assay using ligation-mediated polymerase chain reaction. Both the incidence of apoptotic cells and the level of DNA fragmentation in the testis increased depending on the HU dose, and they were most apparent at the highest dose (400 mg/kg). The incidence of apoptotic cells in the HU-treated group increased continuously and peaked at 12 h, but then decreased gradually, reaching control levels by 48 h. After HU treatment, TUNEL-positive apoptotic cells increased in the seminiferous epithelium of the tubules, and affected cells were found synchronously in the tubules of animals treated with HU. Spermatogonia and spermatocytes were found to be affected selectively. TUNEL-positive cells were found to be stage-specific and were primarily in stage IV-VI tubules. It has been shown that in vivo HU exposure induced testicular germ cell apoptosis dose dependently in a time- and stage-specific manner, and damaged cells appeared to be eliminated by phagocytosis by neighboring cells. Apoptosis of damaged testicular germ cells is apparently a common response to various testicular toxicants therefore protecting the next generations of germ cells from the damaged cell population.

Animals↗
PubMed1999

Stage-specific homeotic vertebral transformations in mouse fetuses induced by maternal hyperthermia during somitogenesis.

To investigate the heat shock effects upon somitogenesis and specification of the vertebral identity, pregnant ICR mice were briefly exposed to 42 degrees C or 43 degrees C at E7.5, E8.5, or E9.5 (noon of the plug day = E0.5). Heat treatment induced embryonic day-specific vertebral transformations whose frequency and severity were dependent on the temperature elevation. Following a heat treatment at E8.5, the vertebral identity of T6 through S1 was shifted anteriorly by one or two segments (posterior transformations). Such shifts were found in more than one-third of the fetuses heat-stressed at 42 degrees C, and in over 90% of those exposed to 43 degrees C. When heated at E7.5, the anterior boundary of vertebral transformations was shifted cranially to cervical levels (C1-C7), and when heated at E9.5, it was shifted caudally to the lower thoracic and lumbar levels (T13-L4). Examination of Hox gene expression domains by in situ hybridization showed that the anterior boundaries of Hoxa-5, Hoxa-7, Hoxc-8, and Hoxc-9 expression domains in the paraxial mesoderm were shifted cranially by one somite segment in embryos heated at E7.5, as compared with the corresponding levels of their expression in control embryos. Such cranial shifts were found for Hoxa-7, Hoxc-8 and Hoxc-9, but not for Hoxa-5, in embryos heated at E8.0. In embryos heated at E8.5, only the expression domains for Hoxc-8 and Hoxc-9 were found to be shifted. The observed stage-specific vertebral transformations and shifts of the Hox gene expression domains were consistent with the temporal colinearity and posterior predominance of Hox gene expression during development. Further histological and cytochemical analyses revealed that heat-induced vertebral transformations may not be a result of induced cell death, but heat-induced transient arrest of cell proliferation and somitogenesis could result in altered expression of Hox genes and subsequently produce vertebral transformations.

Animals↗
PubMed1999

Palmar and plantar pads and flexion creases of genetic polydactyly mice (Pdn).

Attempts to gain a better understanding of the relationship between the epidermal ridge patterns (dermatoglyphics) and flexion creases on the volar aspects of human hands and feet and specific medical disorders led to a search for a suitable animal model, allowing studies of the fetal development of the pertinent structures. A common experimental animal, the rat (Rattus norvegicus), was found to be an excellent candidate, owing to the strong resemblance of the volar pads and flexion creases on its palmar and plantar surfaces to those of human subjects. A hereditary preaxial polydactyly mouse (Pdn) provides an opportunity to study the effects of this malformation on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites over which the dermatoglyphic patterns develop. The hands and feet of the wild-type (+/+) mice show no anomalies, and their major pad and flexion crease configurations correspond to those of normal rats. The heterozygous (Pdn/+) mice, in spite of having a thumb/big toe with a duplicated distal phalanx on their hands/feet, did not display any alterations in palmar/plantar pads. The homozygous (Pdn/Pdn) mice have a protrusion in the thenar area and one to three supernumerary digits on the preaxial portion of both the hands and feet. The effect of these anomalies was found to be limited to the pad and flexion crease configurations in the preaxial areas; the postaxial sites were not affected. The original number of pads on the thenar/first interdigital areas of Pdn/Pdn mice was apparently identical to that of the +/+ and Pdn/+mice. The preaxial protrusion, however, affected the number, size, and location of the pads observed in the newborn mice, resulting in varying pad configurations, such as fused and scattered pads or a pad cluster formed by gathering the neighboring pads. These pad modifications were induced by the preaxial plantar/palmar protrusion only and were not affected by the presence of supernumerary preaxial digits. In view of the similarities in the morphology and fetal development of human and mouse distal limbs, the present study is relevant to human subjects, particularly to the understanding of the significance of dermatoglyphic variations in individuals with specific medical disorders. Future studies of naturally occurring or experimentally induced limb malformations in mice or rats should provide valuable insights into the development of human hands and feet and into factors contributing to their congenital anomalies.

Animals↗
PubMed1999

Apoptosis in congestive heart failure induced by viral myocarditis in mice.

It has recently been speculated that progressive deterioration of left ventricular function in chronic heart failure is due to the ongoing loss of viable cardiac myocytes. However, as there is little direct evidence of significant apoptosis contributing to the pathogenesis in cardiac myocytes in vivo, the significance of apoptosis in heart failure remains to be clarified. We investigated the role of apoptosis in heart failure induced by encephalomyocarditis virus myocarditis. DBA/2 mice were inoculated with the virus (day 0), then killed, and their hearts were extracted 3 to 28 days later. Internucleosomal DNA fragmentation, chromatin binding dye staining, and in situ terminal transferase deoxyuridine triphosphate (dUTP) end-labeling were used to detect apoptosis. Internucleosomal DNA fragmentation (DNA ladder) was clearly demonstrated on days 5 to 14 in the virus-infected hearts when myocardial necrosis and infiltration of mononuclear cells were prominent in the hearts. Apoptotic cells demonstrated morphological changes typical of apoptosis (condensation of chromatin and nuclear fragmentation). Both Fas antigen and Fas ligand immunoreactivity were detected in the infiltrating mononuclear cells. The in situ terminal transferase dUTP end-labeling method demonstrated condensed nuclei of infiltrating mononuclear cells on day 7. However, nuclei of cardiac myocytes surrounded by the cellular infiltration were absent. The main source of apoptotic cells in the heart in mice with viral myocarditis appeared to be the infiltrating mononuclear cells.

Animals↗
PubMed1999

Myxoma of mitral valve associated with infective endocarditis.

A 20-year-old man was hospitalized for persistent fever, embolism, and syncopal attack. Echocardiography demonstrated a tumor on the mitral posterior leaflet. It was removed under extracorporeal circulation following extirpation of thrombus in the right common like artery. The tumor consisted of myxoma and vegetation with bacterial colony. Myxoma and/or vegetation had destroyed the mitral posterior leaflet. Accordingly, it was necessary to perform mitral valve replacement. The postoperative course was uneventful. This is the 14th surgical case of mitral valve myxoma, and the first case of that associated with infective endocarditis.

Adult↗
PubMed1999

PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

Adipocytes↗
PubMed1999

Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring.

Neural tube defects (NTD) are a group of malformations that result from the failure of the neural tube to close early in embryonic development and among the most common congenital malformations in humans. It has been reported that a substantial proportion of NTD in humans can be prevented by folic acid (FA) supplementation prior to conception and during the first months of pregnancy, and myo-inositol (MI) was shown to reduce the incidence of NTD in curly tail mice which are not prevented by FA. Brief maternal hyperthermia (HT) early in pregnancy has been implicated in NTD both in humans and laboratory animals, and anterior NTD including exencephaly and anencephaly are induced frequently when pregnant mice are exposed to HT. We examined the effect of FA or MI supplementation of pregnant mice on the occurrence of heat-induced NTD in the offspring. When pregnant mice were treated with FA (3 mg/kg) daily from gestational day (GD) 0.5 through GD 9.5 and heated at GD 8.5, the prevalence of NTD in the fetuses (26.6%) was significantly lower than the corresponding figure in the HT alone group (38.6%; P < 0.05). However we failed to detect the preventive effect of MI (500 mg/kg). The results of this study suggest that prenatal FA supplementation decreases HT-induced NTD in mice and sufficient FA intake during early pregnancy may be recommended to avoid the birth of malformed children.

Analysis of Variance↗
PubMed1999

Helicobacter heilmannii associated erosive gastritis.

The spiral bacteria, Helicobacter heilmannii (H. heilmannii), distinct from Helicobacter pylori (H. pylori), was found in the gastric mucosa of a 71-year-old man without clinical symptoms. The endoscopic examination revealed erosive gastritis. Rapid urease test from the antral specimen was positive, but both culture and immunohistological staining for H. pylori were negative. Touch smear cytology showed tightly spiral bacteria, which were consistent with H. heilmannii. At the second endoscopy after medication regimen for eradication of H. pylori, inflammation was decreased and the rapid urease test was negative. The second cytology showed no evidence of H. heilmannii. Anti-H. pylori therapy may be a useful medication for H. heilmannii.

Abietanes↗
PubMed1999

Specialty-related disparities of readmission in patients with chronic heart failure: the importance of hospital-clinic cooperation.

OBJECT: The purpose of this study was to elucidate differences in readmission rates and late outcome in outpatients with chronic heart failure treated in different clinical settings. PATIENTS AND METHODS: This study included 65 consecutive patients who were admitted to our CCU due to acute heart failure for the first time and discharged from our institution. After their discharge, 31 were cared for by a cardiologist in the outpatient clinic of our institution (group A) and the other 34 were cared for by a general practitioner in a clinic (group B). The various findings during the acute phase and the follow-up period were retrospectively compared between the two groups. In addition, the incidence of unexpected readmission and prolonged outcomes were compared between the two groups. RESULTS: The patients in group B were older than those in group A, but no other differences were noted in patient characteristics. More patients in group A required more than one hospitalization within 6 months from discharge (group A, 35.5%; group B, 8.9%, p<0.01; follow-up period, 17.1+/-5.9 months). There was no difference in the survival rate between the groups. CONCLUSION: We concluded that stabilized outpatients should receive comprehensive care from a general practitioner to avoid the need for readmission after discharge.

Aged↗
PubMed1999

[Usefulness of pharmacokinetic modulating chemotherapy (PMC) for the postoperative adjuvant therapy of colorectal carcinoma: a preliminary report].

Pharmacokinetic modulating chemotherapy (PMC) using oral UFT and continuous venous 5-FU infusion was administered to 22 resectable patients with Dukes' B2-D colorectal carcinomas. The regimen was arranged as follows: Group A (n = 12) UFT 300-450 mg/day, 5 days a week and 5-FU 440-600 mg/m2/24 hr (750-1,000 mg/body/24 hr) once a week, Group B (n = 10), UFT less than 300 mg/day, 5 days a week, and/ or 5-FU less than 440 mg/m2/24 hr (750 mg/body/ 24 hr) once a week. The control group (Group C, n = 26) was selected at random from among non-PMC cases matched for other background factors and in which surgery had been performed during the past 4 years. Fifteen out of 26 patients in Group C were treated with 5-FU masked compounds orally. The cumulative 2 year recurrent rates of Groups A, B and C were 8.3%, 52.0% and 50.0%, respectively; the rate of Group A was significantly lower than that of Group B (p < 0.05). Four patients who suffered from PMC-related side effects of grade 1-2 wanted to decrease their dosage of UFT and/or 5-FU. They were registered in Group B. These results suggest that the regimen of Group A was advantageous in improving the prognosis after resection of Dukes' B2-D colorectal carcinoma.

Administration, Oral↗
PubMed1998

Expression of rat DNA (cytosine-5) methyltransferase (DNA MTase) in rodent trophoblast giant cells: molecular cloning and characterization of rat DNA MTase.

Methylation of genomic DNA is involved in the basic methanism of gene inactivation, chromatin organization, X chromosome inactivation and genomic imprinting. A pattern of DNA methylation is maintained in mitotic cells by DNA (cytosine-5) methytransferase (DNA MTase). The DNA MTase has been shown to be also expressed in postmitotic cells such as neurons. In the present report, as an approch to analyzing mechanisms underlying regulation of DNA MTase expression, we first isolated rat DNA MTase cDNA. The isolated cDNA encoded a protein of 1,622 amino acid residues showing 88.3% and 64.2% of homology with mouse and human DNA MTase, respectively. Northern blot analysis showed that DNA MTase mRNA was highly expressed in placenta during mid- to late- pregnancy. We then analyzed the expression of DNA MTase in Rcho-1 cells, a rat choriocarcinoma-derived cell line, which cease cell division but keep replicating genomic DNA when differentiated in vitro. We found that the expression of DNA MTase protein was decreased in terminally differentiated Rcho-1 cells whereas DNA MTase mRNA was consistently expressed. This result suggested posttranscriptional regulation of DNA MTase activity in Rcho-1 cells. The Rcho-1 cells would be a valuable model for studying the regulation of gene expression and function of DNA MTase in postmitotic, differentiated cells.

Amino Acid Sequence↗