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Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

792 records · Page 44Linked to original sources

Studies on the posterior silk gland of the silkworm, Bombyx mori. II. Cytolytic processes in posterior silk gland cells during metamorphosis from larva to pupa.

Cytolytic processes in posterior silk gland cells of the silkworm, Bombyx mori, during metamorphosis from larva to pupa have been studied. During this stage, the wet weight and the amounts of RNA and protein of the gland decrease rapidly and markedly, while the amount of DNA decreases slowly and slightly. The ultrastructural changes observed at the beginning of the prepupal stage consist of the appearance or the increase in the number of autophagosomes containing endoplasmic reticulum (ER), or "early autophagosomes" as we have called them, which seem to be gradually transformed to autolysosomes. A number of usual lysosomes, which frequently contain myelin figures, also appear in the cytoplasm. Sometimes they fuse with each other to form large conglomerates. In the middle of the prepupal stage, a number of smooth membrane-bounded vacuoles appear in cytoplasm. Towards the end of the prepupal stage the partition or sequestration of cytoplasm was observed. Thus large autophagosomes containing cytoplasmic organelles such as rough ER and/or mitochondria are formed. The nucleus is partitioned in a similar way by smooth membranes, and then autophagosomes containing condensed chromatin blocks are formed. These various kinds of autophagosomes, or "late autophagosomes" as we have generally called them, are continuously released into the hemolymph until the gland is completely disintegrated.

Animals↗

Studies on the posterior silk gland of the silkworm, Bombyx mori. 3. Ultrastructural changes of posterior silk gland cells in the fourth larval instar.

The development of the cells in the posterior silk gland of the silkworm, Bombyx mori, during the fourth larval instar has been studied. In the early stages of this instar, the wet weight of the gland and the amounts of RNA, DNA, and protein per animal increase logarithmically until they reach a stationary state at about 72 hr. At around 96 hr of the fourth instar, the larvae enter the molting state, which lasts for about 24 hr until the fourth ecdysis. Towards the end of the molt stage, the growth of the silk gland is resumed. Electron microscopical observation shows that in the early intermolt stage the cytoplasm is filled with free ribosomes and with rough endoplasmic reticulum (ER), first of the lamellar type (0-6 hr) and then of the vesicular or tubular type. The Golgi apparatus also is well developed. At the beginning of the molt stage (90-96 hr), however, most of the ER becomes lamellar in type, concentric lamellar structures being occasionally observed, and the Golgi vacuoles disappear. Autophagosomes and lysosomes increase markedly and the apical portion of the cytoplasm becomes extensively vacuolated; this suggests that the secretory activities are completely depressed, and pronounced degenerative changes appear during the molt stage. Towards the end of the molt stage, large lamellar ER elements are fragmented into smaller lamellae and there is a pronounced increase in the number of free ribosomes.

Animals↗

Clinical results with beta-methyl-p-(123I)iodophenylpentadecanoic acid, single-photon emission computed tomography in cardiac disease.

This study was undertaken to evaluate the relationships, between myocardial perfusion and metabolism. Simultaneous beta-methyl-p(123I)iodophenylpentadecanoic acid (123I-BMIPP) and thallium 201 myocardial single-photon emission computed tomography (SPECT) were performed in 25 patients with myocardial infarction (group A) and 16 patients with hypertrophic cardiomyopathy (group B). The severity scores of 123I-BMIPP and 201Tl myocardial SPECT images were evaluated semiquantitatively by segmental analysis. In Group A, dissociations between thallium- and 123I-BMIPP-imaged defects were frequently observed in patients with successful reperfusion compared with those with no reperfusion and those with reinfarction. In four patients with successful reperfusion, repeated 123I-BMIPP and 201Tl myocardial SPECT showed gradual improvement of the 123I-BMIPP severity score compared with the thallium severity score. In group B, dissociations between thallium- and 123I-BMIPP-imaged defects were also demonstrated in hypertrophic myocardium. In addition, nonhypertrophic myocardium also had decreased 123I-BMIPP uptake. In groups A and B, 123I-BMIPP severity scores correlated well with left ventricular function compared with thallium severity scores. These findings indicate that 123I-BMIPP is a suitable agent for the assessment of functional integrity, because left ventricular wall motion is energy dependent and 123I-BMIPP may reflect an aspect of myocardial energy production. This agent may be useful for the early detection and patient management of various heart diseases as an alternative to positron emission tomographic study.

Adult↗

Alcohol dehydrogenase: a new sensitive marker of hepatic centrilobular damage.

To determine whether serum alcohol dehydrogenase (ADH) activity reflects hepatic damage of centrilobular region (zone 3), the rats were given either bromobenzene (BB) or allyl alcohol (AA) IP to produce the pericen tral or periportal necrosis respectively. After AA or BB serum alanine aminotransferase (ALT) activity showed no significant difference between the two groups. By contrast, serum ADH and glutamate dehydrogenase (GLDH) activities were elevated preferentially in the BB treated rats. However, AA administration to rats also resulted in a significant increase in GLDH activity, whereas ADH activity was only slightly elevated when compared to controls. Moreover, acute ethanol administration to rats resulted in a significant elevation of the serum ADH activity, whereas serum GLDH and ALT activities remained normal. These data suggest that serum ADH activity appears to be a sensitive and specific marker of hepatic centrilobular damage.

1-Propanol↗

Diagnostic performance of myocardial contrast echocardiography for detection of stunned myocardium.

Improvement in regional wall motion after acute myocardial infarction has been described up to 2 to 3 weeks after the acute event despite restoration of blood flow by early successful reperfusion therapy. The prospective identification of potentially reversible ventricular dysfunction caused by stunned myocardium has significant clinical implications. Twenty-seven patients with acute myocardial infarction underwent myocardial contrast echocardiography (MCE) before, immediately after, and 4 weeks after successful reperfusion therapy. MCE was performed by imaging a parasternal short-axis view during intracoronary arterial injection of 2 ml sonicated ioxaglate (Hexabrix-320). The contrast defect area and contrast-filled area before reperfusion were defined as the risk area and noninfarct area, respectively. The normalized gray level was defined as the ratio of the gray level in the risk area/gray level in the noninfarct area. In 21 patients, wall motion was akinetic or dyskinetic immediately after reperfusion, and 10 of 21 patients in whom wall motion recovered during the chronic stage were defined as patients with stunned myocardium. In patients who showed asynergic wall motion immediately after reperfusion, MCE predicted the recovery of left ventricular wall motion (stunned myocardium) during the chronic stage with a sensitivity of 77%, specificity of 100%, and predictive accuracy of 86%, when a normalized gray level of more than 0.4 was presumed to predict stunned myocardium. We conclude that MCE provided the prospective identification of potentially reversible ventricular dysfunction caused by stunned myocardium, and wall motion in the area of nonenhanced myocardium on MCE immediately after reperfusion is not expected to show reversible dysfunction.

Adult↗

Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of hormone-like glycoproteins that regulate haematopoietic cell proliferation and differentiation, and G-CSF almost exclusively stimulates the colony formation of granulocytes from committed precursor cells in semi-solid agar culture. Recently, Nomura et al. have established a human squamous carcinoma cell line (designated CHU-2) from a human oral cavity tumour which produces large quantities of CSF constitutively, and the CSF produced by CHU-2 cells has been purified to homogeneity from the conditioned medium. We have now determined the partial amino-acid sequence of the purified G-CSF protein, and by using oligonucleotides as probes, have isolated several clones containing G-CSF complementary DNA from the cDNA library prepared with messenger RNA from CHU-2 cells. The complete nucleotide sequences of two of these cDNAs were determined and the expression of the cDNA in monkey COS cells gave rise to a protein showing authentic G-CSF activity. Furthermore, Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G-CSF gene in CHU-2 cells.

Amino Acid Sequence↗

Long-term circulatory support to promote recovery from profound heart failure.

In profound heart failure, ventricular assist systems (VAS) have been used to maintain the systemic circulation and promote recovery of the failing heart. The authors' data suggest that the heart may not recover sufficiently if the patient needs left ventricular assist beyond 10 days. Recently, the authors treated six patients who were supported by VAS more than 3 weeks and were weaned from VAS. Four of six patients were weaned from VAS and continue well, despite marginal cardiac function. In the other two patients, the natural heart did not sustain stable recovery, but their general conditions made them fit to be candidates for heart transplantation. Based on these data, long-term support should be considered to promote recovery of heart function with the use of VAS for profound heart failure.

Adolescent↗

A pitfall in ultrafast CT scanning for the detection of left atrial thrombi.

We studied 41 patients with mitral stenosis by ultrafast CT (UFCT) and transesophageal echocardiography to detect left atrial thrombi. Cardiac UFCT was performed twice after contrast medium injection to obtain early (during injection lasting 40-60 s) and late (approximately 5 min after beginning injection) phase images. There were 10 patients (24%) in whom a filling defect detected in the early phase disappeared in the late phase. The site of filling defects was the left atrial appendage in nine patients and the left atrium in one patient. All of the filling defects were in the ventral side of the left atrium. Furthermore, all of those patients had chronic atrial fibrillation. Transesophageal echocardiography revealed no thrombus in the area of the filling defect in the early phase. We believe that blood stasis existed in those patients. This finding leads to a false-positive result when only early phase images are obtained. The diagnosis of thrombi should be made only when a filling defect is observed in both phases. Late phase scanning is necessary in the diagnosis of left atrial thrombi.

Adult↗

Immunohistochemical localization of microcystin-LR in the liver of mice: a study on the pathogenesis of microcystin-LR-induced hepatotoxicity.

The relationship between the intralobular sites of hepatotoxic injury and the distribution of microcystin-LR (MCLR), an inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A), was examined using an immunohistochemical method with a monoclonal antibody specific to MCLR on the livers of mice receiving a single i.p. injection of the MCLR. Immunoblotting and high-performance liquid chromatography analyses of liver extracts were also performed to determine the binding form of MCLR to PP1 and PP2A (MCLR-PP1/PP2A adducts) and free MCLR. Immunohistochemistry revealed a discernible intensity of staining in the centrilobular regions where hemorrhage and apoptosis occurred. In these regions, immunopositivity was evident in the cytoplasm and nuclei of the hepatocytes; some apoptotic cells were also immunopositive. In contrast, coagulative necrosis, which was mainly evident in the midlobular regions, was completely negative. Analysis of liver extracts demonstrated MCLR-PP1/PP2A adducts, but free MCLR was below detection limit. These results suggest that the immunohistochemical localization of MCLR in centrilobular hepatocytes is closely associated with the onset of hemorrhage and apoptosis and is related to adduct formation. The occurrence of coagulative necrosis however might also be related to other factors such as ischemia/hypoxia.

Animals↗

Acute toxicity of an anti-Fas antibody in mice.

By histopathologic examination of various organs in 3 normal strains, C3H/HeN, ICR, and DBA/1J, of mice treated intravenously once with anti-Fas antibody (Jo2), we failed to determine any target organ, except the liver, responsible for the acute lethality induced by the Fas/anti-Fas antibody interaction. However, we could show the presence of Fas-mediated apoptosis in other organs aside from the liver and normal mouse strain differences in susceptibility to anti-Fas antibody. Among these strains, C3H/HeN was the most susceptible to the antibody, followed by ICR and DBA/1J. We observed Fas-mediated apoptosis in the liver, spleen, thymus, lymph nodes, Peyer's patch, intestine, skin, coagulation glands, ovary, uterus, and vagina in all 3 strains and additionally in the epididymides and seminal vesicles in the DBA/1J strain. We also demonstrated that Fas-mediated apoptosis of small lymphocytes in the mantle zone of splenic lymphatic follicles preceded that of the hepatocytes or thymic cells. Since cellular damage was most severe in the liver among all the apoptotic organs in the 3 mouse strains, liver injury induced by anti-Fas antibody is speculated to play a significant role in the death.

Animals↗

Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion.

The deepest invasive portion of colorectal carcinoma (CRC) is considered to be the part, which ultimately will invade, spread locally and give metastasis. We have previously reported that histologic differentiation at the deepest invasive portion of CRC closely correlate with metastatic potential and is useful in understanding the curability of endoscopic mucosal resection (EMR). The aim of this study is to clarify the conditions of curative EMR for CRC with submucosally (sm) massive invasion. A total of 521 cases with sm invasive CRC (Group A, 470 surgically resected cases; Group B, 51 followed-up cases after EMR) were studied. The depth of sm invasion was defined as the practically measured distance from muscularis mucosae. Histologic subclassification was performed at the deepest invasive tumor margin as: well-differentiated (W), moderately differentiated (M) and poorly differentiated (Por). By assessing glandular configuration and cellular arrangement, M type was further subdivided into two different groups; moderately-well differentiated (Mw) and moderately-poorly differentiated (Mp). In group A, lymph node (LN) metastasis was detected in 45 (9.6%) of 470 cases. W or Mw lesions showed LN metastasis in 4.9% (19/388). Mp or Por lesions showed LN metastasis in 37.3% (25/67) (W/Mw vs Mp/Por; p<0.01). Of 45 cases with LN metastasis that could be measured the practical distance of sm invasion, W or Mw lesions showed no LN metastasis in cases within 1,500 micrometer invasion. However, Mp or Por lesions showed LN metastasis in cases within 1,500 micrometer invasion (5/15, 33.3%, minimum 400 micrometer invasion; so-called scanty invasion). In group B, none of 51 cases died of LN metastasis and showed no other metastasis, although 17 cases (33.3%) showed an sm invasion more than 1,500 micrometer. These results indicated that CRC even with sm massive invasion can be cured by complete EMR on conditions that the depth of sm invasion is within 1,500 micrometer and histologic grade at the deepest invasive portion is W or Mw, if there are no vessel involvement. However, cases with Mp or Por grade were not curative by EMR, even if they showed an sm scanty invasion.

Colorectal Neoplasms↗

Rudimentary meningocele presenting with an annular alopecia.

Rudimentary meningocele (RM) is a relatively rare developmental anomaly in which meningotherial elements are found in the skin. We present a case presenting with an annular alopecia over a rudimentary meningocele. Due to the occasional presence of connection or relationship to the central nervous system in RM, knowledge of the various clinical appearances including annular alopecia is clinically important.

Alopecia↗

Photodynamic therapy for corneal neovascularization using topically administered ATX-S10 (Na).

BACKGROUND AND OBJECTIVE: We investigated the effect of photodynamic therapy (PDT) using topically administered ATX-S10(Na) on corneal neovascularization (CoNV). MATERIAL AND METHODS: Rabbit eyes with induced CoNV were treated with ATX-S10(Na) eye drops (10 mg/mL) every 5 minutes, 5 to 25 times. Five to ninety minutes after topical administration, the CoNV were irradiated with a diode laser using a wavelength of 670 nm. RESULTS: The CoNV were occluded fluorescein angiographically in 7 of 16 treated eyes. The eyes having occluded, CoNV were irradiated using fluence of 510-1019 J/cm2 within 20 minutes of eye-drop administration. However, the effect was more variable than what we found using systemic administration in our previous investigation. CONCLUSIONS: Experimental CoNV was occluded by photodynamic therapy using topically administered ATX-S100(Na), suggesting this modality as a possible treatment for CoNV avoids the side effects found with systemic administration of the dye. Further efforts to improve the eye drops in terms of pH and osmotic pressure are needed to achieve increased dye accumulation.

Administration, Topical↗

Biological role of thymidine phosphorylase in human astrocytic tumors.

Thymidine phosphorylase (TP) has strong angiogenic activity and is overexpressed in a wide variety of malignant tumors. To elucidate the role of TP in human astrocytic tumors, we immunohistochemically investigated the expression of TP in 62 astrocytic tumors (12 astrocytomas, 12 anaplastic astrocytomas and 38 glioblastomas). Fifty-five astrocytic tumors (88.7%) were immunopositive for TP. The level of TP-expression was significantly correlated with the malignancy grade of astrocytic tumors; most of malignant gliomas highly expressed TP, while a small number of cells were positive in low grade astrocytomas (p < 0.001). Using double-immunostaining, we clarified that TP-expression was predominantly detectable in macrophages. There was no significant correlation between MIB-1 labeling index and TP-expression. However, TP-expression and the microvessel density were well correlated. These suggest that TP, mainly produced by the infiltrated macrophages, may play an important role in the progression of astrocytic tumors via neovascularization. Inhibitor of TP may represent a therapeutic modality for treating malignant gliomas.

Antigens, CD↗

Circular dichroism studies of the coenzyme environment in the active sites of mutant forms of the beta-subunit in the tryptophan synthase alpha 2 beta 2 complex.

The circular dichroism has been used to evaluate the effect of mutation on the environment of the pyridoxal phosphate coenzyme in the active site of the beta-subunit in the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. Seven mutant forms of the alpha 2 beta 2-complex with single amino acid replacements at residues 87, 109, 188, 306, and 350 of the beta-subunit have been prepared by site-directed mutagenesis, purified to homogeneity, and characterized by absorption and circular dichroism spectroscopy. Since the wild type and mutant alpha 2 beta 2 complexes all exhibit positive circular dichroism in the coenzyme absorption band, pyridoxal phosphate must bind asymmetrically in the active site of these enzymes. However, the coenzyme may have an altered orientation or active site environment in five of the mutant enzymes that display less intense ellipticity bands. The mutant enzyme in which lysine 87 is replaced by threonine has very weak ellipticity at 400 nm. Since lysine 87 forms a Schiff base with pyridoxal phosphate in the wild type enzyme, our results demonstrate the importance of the Schiff base linkage for rigid or asymmetric binding. Although the mutant enzymes display spectra in the presence of L-serine that differ from that of the wild type enzyme, addition of alpha-glycerol 3-phosphate converts the spectra of two of the mutant enzymes to that of the wild type enzyme. We conclude that this alpha-subunit ligand may produce a conformational change in the alpha-subunit that is transmitted to the mutant beta-subunits and partially corrects conformational alterations in the mutant enzymes.

Base Sequence↗

[Diagnosis of coronary artery dehiscence and pseudoaneurysm after modified Bentall operation by Doppler color flow imaging: a case report].

This 48-year-old man presented with anterior chest and back pain in 1981. He was treated with replacement of the ascending aorta and aortic valve under a diagnosis of dissection of the ascending aorta with severe aortic regurgitation. He underwent modified Bentall reoperation for the dilation of the aortic root in 1991. Postoperative two-dimensional echocardiography was performed because of sustained atrial flutter. An echo-free space was detected between the aorta graft and aorta wrapping on the short-axis view. Doppler color flow imaging revealed blood flow from the left coronary artery graft into the echo-free space. This leakage was suspected to be the cause of the echo-free space. Transesophageal echocardiography was performed to conform this hypothesis, which revealed blood flow from the left coronary artery graft into the echo-free space in systole and flow into the left coronary artery graft from the echo-free space in diastole.

Anastomosis, Surgical↗