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Biomedical subjects

S Asakura

Publications and source records attributed to S Asakura.

At least 55 records · Page 3Linked to original sources

[Immunohistochemical study of transforming growth factor-beta and central fibrosis in T1 adenocarcinoma of the lung].

Transforming growth factor-beta (TGF-beta) is known as the growth factor that stimulates the multiplication and accumulation of extracellular matrix. Recently, TGF-beta also has been found to have the ability to control the growth and metastatic potential of cancer cells. It is known that central fibrosis frequently occurs in pulmonary adenocarcinoma and the prognosis becomes poorer as fibrosis become more hyalinized. To estimate the role of TGF-beta in the formation of central fibrosis in pulmonary adenocarcinoma and its influence on the prognosis of patients with pulmonary adenocarcinoma, we performed an immunohistochemical study of TGF-beta in 51 cases of T1 pulmonary adenocarcinoma. Positive stain for TGF-beta was shown in 31 cases, and negative stain was shown in 20 cases. In patients with Stage I, T1 pulmonary adenocarcinoma, the post operative survival curve was compared between positive and negative cases of TGF-beta, and the result showed a tendency toward poorer prognosis in positive cases of TGF-beta. Twenty-four of 51 cases of T1 pulmonary adenocarcinoma had central fibrosis. Twenty of 24 cases with central fibrosis showed positive stain for TGF-beta. It was proven that the appearance of central fibrosis was significantly related to positive stain for TGF-beta in T1 pulmonary adenocarcinoma. According to these results, it is suggested that TGF-beta plays some role in the formation of central fibrosis in pulmonary adenocarcinoma and TGF-beta is possibly a prognostic factor for patients with pulmonary adenocarcinoma.

Adenocarcinoma↗

Localization of vitronectin- and fibronectin-receptors on cultured human glioma cells.

Utilizing a human astrocyte-derived glioma cell line, we have demonstrated the presence of a vitronectin receptor, alpha v beta 3, and a fibronectin receptor, alpha 5 beta 1, on the surface of the cells spreading on the respective adhesion molecules by immunohistochemical analyses. By phase-contrast microscopy, these receptors were found to be expressed predominantly in the focal contact-like area, suggesting that they were involved in the spreading of the cells upon contact with these adhesion molecules. Interestingly, they appeared to have differential functions and roles as integrins as evidenced by different time-dependent distribution profiles on the cell surface in the serum-containing medium. Furthermore, both vitronectin and fibronectin seem to have chemotactic effects onto the glioma cells as observed in a Boyden chamber study. Although these receptors are not expected to be present on the surface of astrocytes under physiological conditions, they may be expressed thereon and involved in gliosis when the cerebral vasculature is traumatized and, thereby, blood proteins, including vitronectin and fibronectin, come into contact with the astrocytes.

Cell Adhesion↗

Posterior mediastinal endodermal sinus (yolk sac) tumor in a female patient.

Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is uncommon. Most patients are young and male, and the great majority of tumors are found in the anterior mediastinum. We report a case of primary posterior mediastinal endodermal sinus tumor occurring in a female patient. Surgical excision was performed and three courses of combination chemotherapy were subsequently given. The serum alpha-fetoprotein level returned to normal.

Adolescent↗

Effects of dietary restriction on induction of unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) in rat liver.

The effects of dietary restriction on the induction of unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) were studied in the hepatocytes of F344 rats exposed in vivo to dimethylnitrosamine (DMN) or CCl4. The animals were given food ad libitum, a restricted amount of food (4 g/rat/overnight) or no food. Hepatocytes were isolated 2 h after oral administration of DMN at a dose of 5 mg/kg body weight and 48 h after oral administration of CCl4 at a dose of 400 mg/kg body weight, and incubated for 4 h in Williams' medium E supplemented with either [3H]thymidine for UDS or 5-bromodeoxyuridine for RDS. UDS was determined by autoradiography and RDS was determined by the immunoenzymatic staining method. The background levels of UDS (net grains/nucleus) and RDS (cells in S phase) in control were -12.4 and 0.64% for ad libitum feeding, -6.8 and 0.04% for restricted feeding, and -8.1 and 0% for fasting. UDS induced by DMN and RDS induced by CCl4 were 19.4 and 3.3% for ad libitum feeding, 34.5 and 10.4% for restricted feeding, and 47.8 and 15.1% for fasting. DMN demethylase activity in rat liver was also found to increase with dietary restriction. These results indicate that dietary restriction modulates the responses of UDS and RDS in the liver of rats.

Animals↗

Cumulative effects of chromosome aberrations and sister chromatid exchanges in rat liver induced in vivo by heterocyclic amines.

Cumulative effects of chromosome aberrations and sister chromatid exchanges (SCEs) were studied in hepatocytes of F344 rats exposed in vivo to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day or 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day. Hepatocytes were isolated 24 h after 1, 7, 14 or 28 repeated doses (once a day) by gastric intubation and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 h. Multiple treatment with IQ or nitro-IQ induced significant chromosome aberrations time- and dose-dependently, the maximum frequency of chromosome aberrations in metaphase cells being 39 and 33% respectively, while that in controls was 1.1%. Single treatment with IQ or nitro-IQ induced significant SCEs dose-dependently, the maximum frequency being 0.83 and 0.79 per chromosome respectively, while the control value was 0.51. Multiple treatment with nitro-IQ induced significant SCEs to a plateau level of 0.90 per chromosome. Cytogenetic damage in the liver by IQ was greater than that by nitro-IQ. These results show that this assay of chromosome aberrations and SCEs in rat liver in vivo without partial hepatectomy or mitogen treatment in vivo is a sensitive method for evaluating the cumulative tumor-initiating activities of carcinogenic heterocyclic amines at low doses and should be useful for the detection of unknown hepatocarcinogens.

Amines↗

Effect of terfenadine on substance P and vasoactive intestinal polypeptide concentrations in nasal secretions from patients with nasal allergy.

Before terfenadine treatment, the mean substance P and vasoactive intestinal polypeptide (VIP) concentrations in nasal secretions from nasal allergy patients tended to be higher than the values of healthy subjects. During terfenadine treatment, the mean substance P concentrations in nasal secretions from patients allergic to house dust or pollen were significantly decreased to 62 and 39% of the initial values, respectively. The mean VIP concentrations in nasal secretions from the house dust allergy patients and the pollen allergy patients were significantly decreased to 52 and 18% of the initial values, respectively. Plasma substance P and VIP concentrations were not affected by nasal allergic symptom and terfenadine treatment.

Adolescent↗

Immunohistochemical localization of transforming growth factor-beta 1 in the nonnecrotizing granulomas of pulmonary sarcoidosis.

Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by the formation of nonnecrotizing granulomas in affected tissues, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming growth factor-beta 1 (TGF-beta 1) is a potent cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha 5 beta 1 fibronectin receptor. The role of TGF-beta 1 in promoting lung fibrosis in the setting of pulmonary sarcoidosis has not yet been investigated. Accordingly, we determined the extent and distribution of TGF-beta 1 in lung tissue obtained from seven patients with clinical and histologic features of pulmonary sarcoidosis. The tissue distributions of TGF-beta 1, the TGF-beta 1 binding proteoglycan decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor were assessed immunohistochemically. In all cases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta 1. We further demonstrated decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue surrounding the lesions. TGF-beta 1 staining was also observed in bronchiolar epithelial cells, hyperplastic Type II pneumocytes, and occasional alveolar macrophages. This study demonstrates enhanced tissue localization of TGF-beta 1 and related extracellular matrix proteins associated with the nonnecrotizing granulomas of pulmonary sarcoidosis. Through its actions on matrix protein synthesis, TGF-beta 1 may modulate the fibrotic repair process accompanying granuloma healing in sarcoidosis.

Adult↗

Enzyme immunoassay of motilin in human plasma.

A sensitive and specific double-antibody enzyme-linked immunoassay (EIA) for detecting a motilin-like immunoreactive substance (M-IS) in human plasma has been developed. In competitive reactions, the motilin antibody was incubated with a plasma sample (or motilin standard) and beta-D-galactosidase-linked synthetic motilin. Free and antibody-bound enzymes were separated using an anti-rabbit IgG-coated immunoplate. Enzyme activity on the plate was determined by fluorophotometric analysis. This immunoassay allows the detection of 20 to 200 fmol/ml (54 to 540 pg/ml) of motilin. The mean level of M-IS detected in human plasma was 53.9 +/- 25.6 pg/ml.

Adult↗

Agnogenic myeloid metaplasia with extramedullary hematopoiesis and fibrosis in the lung. Report of two cases.

Agnogenic myeloid metaplasia (AMM) is a chronic hematologic disorder with a long clinical course, characteristically accompanied by extramedullary hematopoiesis (EMH) in various organs, most commonly the spleen and liver. We describe two cases of AMM with clinically significant and ultimately fatal EMH and associated fibrosis in the lung and pleura. The literature on AMM and EMH involving the lung and pleura is reviewed. Three similar cases were found.

Aged↗

Development of a novel drug release system, time-controlled explosion system (TES). I. Concept and design.

A novel controlled drug release system. Time-Controlled Explosion System (TES) has been developed. TES has a four-layered spherical structure, which consists of core, drug, swelling agent and water insoluble polymer membrane. TES is characterized by a rapid drug release with a precisely programmed lag time; i.e. expansion of the swelling agent by water penetrating through the outer membrane, destruction of the membrane by stress due to swelling force and subsequent rapid drug release. For establishing the concept and development strategy, TES was designed using metoprolol and polystyrene balls (size: 3.2 mm in diameter) as a model drug and core particles. Among the polymers screened, low-substituted hydroxypropylcellulose (L-HPC) and ethylcellulose (EC) were selected for a swelling agent and an outer water insoluble membrane, respectively. The release profiles of metoprolol from the system were not affected by the pH of the dissolution media. Lag time was controlled by the thickness of the outer EC membrane; thus, a combination of TES particles possessing different lag times could offer any desired release profile of the model compound, metoprolol.

Chemistry, Pharmaceutical↗

[Thoracoscopic treatment of mediastinal thymic cyst].

A mediastinal thymic cyst was excised under thoracoscope in a 66 year-old man. Mass lesion was noted in the left anterior mediastinum on chest X-p during a screening examination. Based on the findings of the chest CT and MRI, the mass was diagnosed as a cyst containing low fat and low protein fluid without solid tissue. This lesion was diagnosed as a mediastinal thymic cyst. Under general anesthesia, the thoracoscopy was inserted to the left thoracic cavity. Then, the cyst was resected sharply and bluntly with pair of scissors, while electric coagulation was performed as needed. In cases of mediastinal thymic cyst, it is possible to completely resect the cyst by thoracoscopic treatment, causing minimal surgical invasiveness. Considering that a few thymic cysts are combined with malignant tumor, complete resection of the lesion is required in the treatment of thymic cyst.

Aged↗

Fibrinogen Mitaka II: a hereditary dysfibrinogen with defective thrombin binding caused by an A alpha Glu-11 to Gly substitution.

A new type of A alpha Glu-11 to Gly substitution has been identified in a congenitally abnormal fibrinogen, fibrinogen Mitaka II, derived from a 14-year-old female suffering from easy bruising since childhood. Plasma of the patient and fibrinogen purified therefrom were found to clot slowly by thrombin but in a normal fashion by ancrod, a thrombin-like snake venom enzyme. The ancrod-clotted fibrin gels were normally solid and turbid, whereas the thrombin-clotted gels were initially fragile and transparent but became gradually normalized during further incubation. On reverse-phase high-performance liquid chromatography, there was an additional peptide group eluted distinctly later than the corresponding normal fibrinopeptide A in the clot-liquor of the patient's samples. Sequence analysis of these aberrant peptides and isolated A alpha chains of the patient's fibrinogen showed that Glu at position 11 of the abnormal A alpha chain had been replaced by Gly. Studies using 125I-labeled thrombin showed that the binding with thrombin was evidently reduced for her fibrinogen and the aberrant fibrinopeptide A as compared with that for the normal controls, indicating that A alpha Glu-11 may be critical for the fibrinogen-thrombin interaction. Indeed, A alpha Glu-11 of fibrinogen has recently been proposed to stabilize the local conformation, including the beta-turn, and to form a salt bridge between its side-chain carboxyl group and the guanidino group of Arg-173 of thrombin based on crystallographic analyses using analogs of fibrinopeptide A complexed with thrombin (Stubb et al, Eur J Biochem 206:187, 1992 and Martin et al, J Biol Chem 267:7911, 1992).

Adolescent↗

A new type of congenital dysfibrinogen, fibrinogen Bremen, with an A alpha Gly-17 to Val substitution associated with hemorrhagic diathesis and delayed wound healing.

We have identified a new type of A alpha Gly-17 to Val substitution in a congenital dysfibrinogen, fibrinogen Bremen, derived from a 15-year-old boy having manifested easy bruising and delayed wound healing. The functional abnormality was characterized by altered fibrin monomer polymerization, which became evident by increasing the salt concentration and pH. A synthetic tetrapeptide with a sequence of the amino-terminal segment of normal fibrin alpha-chain, Gly-Pro-Arg-Val, substantially inhibited polymerization of both normal and the patient-derived fibrin monomers. A synthetic tetrapeptide with the Bremen type sequence of Val-Pro-Arg-Val inhibited polymerization of the patient's fibrin monomers partially at a peptide: fibrin monomer molar ratio of 4,000:1, and that of normal one at a much higher ratio of 10,000:1. Likewise, a synthetic peptide Ala-Pro-Arg-Val with a replacement of the Gly residue by another aliphatic amino acid Ala inhibited similarly the patient's fibrin monomer polymerization. Thus, the hypothetical two-pronged socket-like structure consisting of the alpha-amino group of the amino-terminal Gly and the guanidino group of an Arg at position 3 of the normal fibrin alpha-chain seems to be restored considerably in the mutant fibrin alpha-chain at low ionic strengths and pH's, despite the replacement of the amino-terminal Gly by another aliphatic amino acid Val.

Adolescent↗

Decreases in substance P and vasoactive intestinal peptide concentrations in plasma of stroke-prone spontaneously hypertensive rats.

In order to study alterations of peripheral substance P (SP) and vasoactive intestinal peptide (VIP) in the immunoreactive nervous system in essential hypertension, plasma SP and VIP concentrations in stroke-prone spontaneously hypertensive rats (SHRSP) at 8, 12, 18, 28, 30, 35 and 48 weeks of age and age-matched Wistar-Kyoto rats (WKY) were measured, using enzyme immunoassays (EIAs). The mean plasma SP concentrations of SHRSP (n = 61) and WKY (n = 58) were 4.9 +/- 1.2 fmol/ml and 6.6 +/- 1.9 fmol/ml, respectively. The value of SHRSP was significantly lower than that of WKY (p < 0.01). The mean SP concentration of young SHRSP was significantly higher than those of other ages. The mean plasma VIP concentrations of SHRSP (n = 61) and WKY (n = 58) were 0.80 +/- 0.25 fmol/ml and 1.01 +/- 0.32 fmol/ml, respectively. The value of SHRSP was significantly lower than that of WKY (p < 0.01). These decreases in plasma SP and VIP concentrations of SHRSP were observed at all ages. Decreases in the peripheral release of SP and VIP from the endings of SP- and VIP-immunoreactive nerves of SHRSP were seen, and the functional involution of peripheral SP- and VIP-immunoreactive nerves in essential hypertension was suggested.

Animals↗

Cellular fibronectin in plasma: its implications in fibrinogen-associated cryoprecipitation and other related reactions.

Elimination of cryoprecipitable plasma components (cryogels) by cryofiltration from the circulating blood of patients with drug-resistant rheumatoid arthritis (RA) alleviates clinical symptoms including morning stiffness and arthralgia. The cryogels thus isolated from the blood were found to consist mainly of fibrinogen (Fbg) and fibronectin (FN). Analysis by immunoblotting with an anti-cellular FN monoclonal antibody revealed that cellular FN (cFN) co-existed with plasma FN (pFN) in the cryogels derived from the patients. Using an ELISA, we assessed cFN together with the total FN (pFN+cFN) in plasmas and cryogels derived from the patients. The cFN/total FN ratio was distinctly higher in the cryogels than in the plasmas, suggesting that cFN was more readily precipitated than pFN in association with Fbg under cold conditions.

Arthritis, Rheumatoid↗

[A case of benign mesothelioma of the tunica vaginalis testis].

A case of benign mesothelioma of the tunica vaginalis testis is described. A 56-year-old man with no history of asbestos exposure presented with a swelling of the left scrotal content. A physical examination revealed a hydrocele and an induration on the left epididymal head. A cytological examination of the hydrocele fluid demonstrated clusters of mesothelial cells without evidence of malignancy (class III). Left inguinal orchiectomy was performed because a 15 mm papillary pedunculated tumor was seen on the surface of the tunica vaginalis. A microscopic examination showed the papillary and glandular structures composed of cuboidal cells with no cytologic atypia, which were consistent with benign mesothelioma. The patient remains well and free of recurrent disease 10 years after operation.

Diagnosis, Differential↗

Heterozygous abnormal fibrinogen Osaka III with the replacement of gamma arginine-275 by histidine has an apparently higher molecular weight gamma-chain variant.

Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of alpha- and gamma-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal gamma-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 gamma remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).

Adult↗