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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 415 records · Page 23Linked to original sources

Sarcomatoid carcinoma of the small intestine: histologic, immunohistochemical and ultrastructural features of three cases and its differential diagnosis.

Three cases of sarcomatoid carcinoma of the small intestine are presented. One of them was found accidentally in the duodenum of a patient with a well differentiated adenocarcinoma and a malignant lymphoma that were limited to the stomach. The other two cases arose from the ileum. All of the tumors were whitish, soft and ulcerated with focal hemorrhage and necrosis and showed expansive growth. Each tumor consisted of a mixture of polygonal and spindle shaped anaplastic neoplastic cells arranged in sheet, short fascicular or haphazard fashion, with no finding suggesting epithelial differentiation. Special stains demonstrated intracellular mucin in only a small number of tumor cells in two cases, but not in the other case. Immunohistochemically, the tumor cells of two cases at both primary and metastatic sites showed a positive immunoreaction for cytokeratin and epithelial membrane antigen. In the other case, only a few tumor cells at the metastatic site, but not at the primary site, showed cytokeratin positivity. Various numbers of tumor cells positive for vimentin, alpha-1-antitrypsin (AAT), alpha-1-antichymotrypsin (ACT) and KP-1 were detected in each case. Ultrastructurally, some populations of tumor cells possessed various amounts of tonofilaments with a few intercellular connections between adjacent tumor cells. These cases should be classified as sarcomatoid carcinoma of the small intestine, despite partial or complete loss of epithelial features, and distinguished from the various sarcomas.

Aged↗

Prostaglandin-induced protection of cultured rat gastric cells against ethanol is inhibited by a microtubule inhibitor.

Prostaglandins reduce damage by noxious agents to isolated gastric cells. The mechanism remains unexplained. This study was done to examine involvement of microtubules with prostaglandin-mediated cell protection. Cultured mucus-producing cells of rat gastric mucosa were used. Cultured cells were incubated with 16, 16-dimethyl-prostaglandin E2 (dmPGE2), colchicine, or vehicle alone in calcium-containing (1.3 mM) and calcium-free medium. The cells were then exposed to 8% ethanol. Cell integrity and damage were assessed by 51Cr release and in part by transmission electron microscopy (TEM). Specific 51Cr release was closely related to percentage change of necrotic cells assess by TEM. Cell damage caused by 8% ethanol was greater in medium-containing calcium than in calcium-free medium. dmPGE2 at 10(-5) M inhibited cell damage in calcium-containing medium. Colchicine itself at concentrations up to 10(-5) M did not affect cell integrity, but at 10(-5) M concentration potentiated damage caused by 8% ethanol in calcium-containing medium. Pretreatment with 10(-5) M colchicine abolished the protective effect of dmPGE2. Microtubules may mediate protection by dmPGE2 of cultured gastric cells against ethanol damage.

Animals↗

Sialyl Lewis X analog inhibits eosinophil accumulation and late asthmatic response in a guinea-pig model of asthma.

Preferential eosinophil accumulation is characteristic of airway inflammation in asthma. Although little is known about its mechanism, the effect of a sialyl Lewis X analog on airway eosinophilia was examined in a guinea-pig model of asthma. Guinea-pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed striking airway eosinophilia and a late asthmatic response. In contrast, when guinea-pigs were pretreated intravenously with sialyl Lewis X analog (LX 0104) 1 h before antigen challenge, both eosinophil infiltration in the tracheal wall and the late asthmatic response were significantly inhibited in a dose-dependent manner. In a further in vitro study, LX 0104 significantly suppressed the adhesion of human and guinea-pig eosinophils to human umbilical vein endothelial cells activated with interleukin-1 beta. These results suggest that LX 0104 plays a critical role in antigen-induced airway eosinophilia and the late asthmatic response.

Animals↗

Comparison of adhesion molecule expression on light and normal-density eosinophils from patients with eosinophilia.

Increased numbers of light-density eosinophils (LDEs) are observed in the blood of patients with eosinophilia and are associated with disease activity. LDEs are thought to be metabolically more activate than normal-density eosinophils (NDEs). Recent studies suggest that cytokine-induced eosinophil activation is associated with adhesion molecule expression. The activated state of LDEs may result from increased expression of adhesion molecules. This study compared the expression of eosinophil adhesion molecules on LDEs and NDEs from various diseases characterized by eosinophilia. Expression of very late antigen-4 (VLA-4), lymphocyte function-associated antigen-I (LFA-1) and macrophage antigen-1 (Mac-1) on eosinophils from patients with eosinophilia was increased compared with those from healthy subjects. Mac-1 expression on LDEs was higher than on NDEs. These results suggest that VLA-4 plays a role in selective migration of eosinophils into the inflammatory tissue, and that Mac-1 is associated with activation of eosinophils in eosinophilic diseases.

Cell Adhesion Molecules↗

Enhanced expression of platelet-activating factor receptor on human eosinophils by interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.

The effects of interleukin-3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surface expression of platelet-activating factor (PAF) receptor on eosinophils was examined using a PAF receptor binding assay. Specific binding of [3H]WEB 2086, a specific ligand for PAF receptor, to peripheral blood eosinophils obtained from healthy individuals was significantly increased when the cells were cultured with IL-3, IL-5, or GM-CSF for 12 h, compared with untreated cells. The PAF-induced increase in intracellular calcium ion concentration in eosinophils was markedly augmented by exposure to IL-5 for 12 h. These results suggest that these cytokines modulate the responsiveness of eosinophils to PAF through enhancement of PAF receptor expression on the cell surface.

Calcium↗

Role of interleukin-4 and vascular cell adhesion molecule-1 in selective eosinophil migration into the airways in allergic asthma.

Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosinophils into the airways in allergic asthma, and support the hypothesis described above.

Adult↗

Two new monoterpene glycosides from ku-ding-cha. Inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT).

Two new monoterpene glycosides, kudingosides A and B, were isolated from Ku-Ding-Cha (Ligustrum pedunculare REHD.), together with a known monoterpene glycoside, (S)-lipedoside B-III, and three known phenylethanoid glycosides. Their structures were elucidated by spectroscopic and chemical means. Kudingosides A and B, and (S)-lipedoside B-III inhibited acyl-CoA: cholesterol acyltransferase (ACAT) with IC50 values of 2.70 x 10(-3)M, 2.88 x 10(-3)M, and 2.69 x 10(-4)M, respectively.

Acyclic Monoterpenes↗

[Quality evaluation on Paeoniae radix. I. Quantitative analysis of monoterpene glycosides constituents of Paeoniae radix by means of high performance liquid chromatography. Comparative characterization of the external figures, processing method and the cultivated areas].

The constituents of monoterpene in Paeoniae Radix were analyzed by means of high performance liquid chromatography (HPLC) using hitherto elucidated eight monoterpene glycosides, paeoniflorin 1, oxypaeoniflorin 2, benzoylpaeoniflorin, 3, benzoyloxypaeoniflorin 4, galloylpaeniflorin 5, galloyloxypaeoniflorin 6, albiflorin 7 and lactiflorin 8 and a monoterpene paeoniflorigenone 9. In sixty seven kinds of Paeoniae Radix collected in Japan, China, and South and North Korea those monoterpene constituents 1-9 were found to exist in the amounts of ranging 0.12-9.61% 1, 0.06-10.8% 2, 0.02-0.79% 3, 0.24-0.47% 4, 0.25-2.53% 5, 0.05-2.86% 6, 0.09-2.76% 7, 0.35-0.64% 8 and 0.01-0.49% 9 respectively. In addition, these results obtained by the quantitative analysis were discussed from the viewpoint of the external figures and processing methods.

China↗

[The affinities of mosapramine for the dopamine receptor subtypes in human cell lines expressing D2, D3 and D4 receptors].

The affinities of mosapramine hydrochloride, an iminodibenzyl antipsychotic drug, for dopamine receptor subtypes were determined by human dopamine D2, D3 and D4 receptors expressed in several cell lines and compared with those of other neuroleptics. Tritiated spiperone bound to the membrane of transfected cells in a saturable manner, and the Kd values for dopamine D2, D3 and D4 receptors were 0.021, 0.12 and 0.10 nM, respectively. Mosapramine showed the highest affinities for these receptor subtypes among the antipsychotics tested. The ratio of Ki values between D2 and D3 (D2 Ki/D3 Ki ratio) in mosapramine was higher than that of haloperidol, indicating that the effects of mosapramine on D3 receptors were more potent than those of haloperidol. On the other hand, clozapine, risperidone and raclopride had higher affinity to D4, D2 and D3 subtypes, respectively. The affinities of mosapramine for D4 receptors was 8 times higher than that of clozapine, and the affinity for D3 receptors was 40 times higher than that of raclopride. These results suggest that the effect on D3 receptors may underlie at least a portion of mosapramine's atypical clinical profile.

Antipsychotic Agents↗

Characteristic upregulation of dopamine D1-receptor in rat striatum after 6-hydroxydopamine treatment.

We measured the number of D1-receptors (Bmax) in the striatum whose dopaminergic terminals were destroyed to various degrees by 6-hydroxydopamine (6-OHDA) to clarify the relationship between the degree of denervation and the change in Bmax for D1-receptor. Rats were sacrificed 28 days after 6-OHDA treatment, and [3H]SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine) binding capacity and monoamine content were measured in striatal homogenate. Bmax was significantly upregulated when dopamine content was reduced to less than 5% of that in the vehicle-treated striatum. In contrast, it was significantly decreased when dopamine content was 5-25% of that in the vehicle-treated striatum. The D1-receptors showed either upregulation or downregulation depending on the degree of denervation.

Animals↗

Case report. synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome.

A case of the SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome in a 35-year-old woman is presented. Ignorance of this entity on the part of the physicians treating the patient may have contributed to her having repeated diagnostic procedures and treatment, some of which may have been unnecessary. Dentists are encouraged to suspect the SAPHO syndrome when they encounter a patient with mandibular osteomyelitis together with symptoms involving other bones and skin lesions such as pustulosis or psoriasis.

Acne Vulgaris↗

Effects of ebelactone B, a lipase inhibitor, on intestinal fat absorption in the rat.

Ebelactones A and B, natural products from Streptomyces aburaviensis are potent inhibitors of pancreatic lipase. Lipase is the key enzyme required for the absorption of dietary triglycerides (TG). Ebelactone B inhibited, in a dose-dependent manner, the intestinal absorption of fat after fat-feeding in the rat. The most effective inhibition was observed when the inhibitor was administered at 60 min prior to fat-feeding. When ebelactone B (10 mg/kg) was administered, the serum levels of TG (58%) and cholesterol (36%) were decreased. Since ebelactone B effectively inhibitors absorption of dietary fat, if may provide a promising means for prophylaxis or therapeutics of hyperlipidemia and obesity.

Animals↗

The prognostic importance of nuclear morphometry and the MIB-1 index in rhabdomyosarcoma [corrected].

Both nuclear morphometry and an evaluation of the cell proliferative activity have been reported to be useful tools in predicting prognosis in malignant tumors. There have been few reports, however, on rhabdomyosarcoma regarding these evaluative techniques. We performed nuclear morphometry on 51 tumor specimens obtained either by biopsy or by resection of primary and untreated rhabdomyosarcomas, and we then evaluated MIB-1 staining on 25 of the 51 specimens. The morphometric analysis was semiautomatically performed on hematoxylin- and eosin-stained sections by using a personal computer. The areas, perimeters, and lengths of the major and minor axes of the best fitting ellipse of the nuclei were all measured. In addition, the Form Ell (nuclear ellipsoidity score: minor axis/major axis) was calculated. Using the monoclonal MIB-1 antibody, which detects Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, immunohistochemical studies were performed. The values of the major and minor axes and the Form Ell showed significant differences between each histologic subtype whereas the values of nuclear areas did not. We defined the nucleus whose Form ELL was smaller than 0.25 as spindle-shaped nuclei and then divided all cases into two groups on the basis of the ratio of the spindle-shaped nuclei to the total number of nuclei of the tumor cells. The group with the higher ratio showed a significantly better prognosis (P < 0.05). The same trends were also found in the specimens with an embryonal subtype. Nuclear morphometry was a useful tool in predicting prognosis. In particular, the appearance of spindle tumor cells in rhabdomyosarcoma correlated with a better prognosis.

Adolescent↗

Detection of transforming growth factor-beta in sputum from patients with bronchial asthma by eosinophil survival assay and enzyme-linked immunosorbent assay.

BACKGROUND: We have shown that interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are present in sputum from patients experiencing acute asthma attacks, by eosinophil survival assay. The viability of guinea-pig eosinophils was significantly increased in the presence of such sputum extracts after 3 days' culture, and it was inhibited by the addition of anti-IL-5 and anti-GM-CSF antibodies. However, the contribution of IL-5 to the increase in eosinophil viability was less than expected from the values of IL-5 measured by enzyme-linked immunosorbent assay (ELISA). Therefore, we speculated that something in sputum inhibited the function of IL-5. OBJECTIVE: Transforming growth factor-beta (TGF-beta) was the only cytokine we tested that inhibited the prolongation of survival of guinea-pig eosinophils induced by IL-5. The objective of this study is to detect TGF-beta in the same sputum. METHODS: Guinea-pig eosinophils were cultured with or without anti-TGF-beta antibody in the presence of sputum extracts, and the eosinophil viability was counted after 3 days. Measurement of TGF-beta 1 in sputum was performed by ELISA. RESULTS: Eosinophil viabilities with and without anti-TGF-beta antibody were 79.7 +/- 2.9% and 69.0 +/- 2.7%, respectively, and the difference between them was statistically significant (P < 0.05, n = 9). The concentration of TGF-beta 1 in the sputum was 21.7 +/- 3.3 ng/mL (n = 9). CONCLUSION: These observations suggest that TGF-beta is present in sputum from patients with bronchial asthma.

Adult↗

[Effects of traumatic subarachnoid hemorrhage on pathological properties in diffuse brain injury: a comparison with aneurysmal subarachnoid hemorrhage].

As a result of recent advances in continuous monitoring equipment, it has been reported that vasospasm (VS) and delayed ischemic neurological deficit (DIND) occur as frequently in traumatic subarachnoid hemorrhage (TSAH) as in subarachnoid hemorrhage due to ruptured intracranial aneurysm (ASAH), and these VS and DIND have been reported to affect the outcome of TSAH adversely in many cases. When we compared TSAH secondary to diffuse brain injury (DBI) with ASAH, however, these two conditions were evidently different from each other in nature. Then we compared laboratory data, clinical course, and outcomes of TSAH associated with DBI with those of ASAH, to determine whether TSAH results in poor outcomes of DBI. On CT scans, patterns of SAH distribution were different from each other, and SAH was detected in 76% of the patients with ASAH on day 4, whereas only 2.0% of the patients with TSAH had detectable SAH on day 3. The incidence rates of detectable SAH in both groups remained significantly different from each other after day 2. The cerebral blood flow (CBF) decreased to around 75% of the normal flow in the acute stage of ASAH, and it decreased further to around 65% in the subacute stage. In TSAH, in contrast, CBF varied widely among the patients. The average CBF decreased to about 70% in the acute stage, and then it increased to around the lower limit of the normal range in the subacute stage. The urinary output and serum concentration of low molecular protein compositions in TSAH were markedly different from those in ASAH. In addition, the contour of a low density area (LDA) in CT scans in the subacute-chronic stage was the same as that of the area supplied by the artery being constricted due to cerebro-vascular spasm in ASAH. In TSAH, in contrast, hardly any LDA had a form that was suggestive of this conjuction, with cerebro-vascular spasm and the incidence rate of LDAs was significantly different from that for ASAH. About 30% of the patients with ASAH had ventricular enlargement, which was diagnosed as normal pressure hydrocephalus by cisternography, in the chronic stage. Surgical shunting was effective for these patients. In TSAH, ventricular enlargement was observed in more than 50% of the patients, but almost none of these patients underwent surgical shunting, because it resulted from cerebral atrophy. Regardless of causes of SAH, the severer SAH was, the more often patients had a poor outcome. The outcome of TSAH was, however, significantly poorer than that of ASAH. When SAH was traumatic, it disappeared by the time VS developed and, in addition, changes in CBF and the form and incidence rate of LDAs were different from those in ASAH. We concluded that, although TSAH is an adverse prognostic factor for DBI, it does not contribute to poor outcomes of DBI by giving rise to DIND caused by VS.

Acute Disease↗

[Pseudoxanthoma elasticum with pulmonary calcification].

A woman born in 1920 had had multifocal, yellowish nodules on her skin since childhood and had been given a diagnosis of pseudoxanthoma elasticum. When she was 59-year-old, a diffuse granular shadow was seen on a chest radiograph. When she was 74-year-old, she presented with dyspnea on exertion. A thoracoscopic lung biopsy was done. Histologic examination of the lung tissue revealed small calcified nodules scattered in the alveolar septa. Pseudoxanthoma elasticum is a systemic, hereditary disorder that usually affects elastic fibers of the skin, eye, and cardiovascular system. It's incidence is quite low: 1 out of 160,000-1,000,000 population. Very few cases of pseudoxanthoma elasticum with pulmonary involvement have been reported, and we know of no previous case in Japan in which pulmonary microcalcification was confirmed histologically.

Aged↗

Positive reaction of monoclonal antibody (TO73) with resistant leukemic cells.

We previously reported the characteristics of a murine monoclonal antibody (TO73) against the multidrug-resistant (MDR) human leukemic cell line. In the present study, we have studied the clinical significance of TO73 by examining its reactivity with primary and relapsed leukemic cells. Of 20 patients with primary leukemia and 15 patients with relapsed leukemia, none and four cases, respectively, reacted with TO73 (p < 0.05). Furthermore, three of the four positive cases were also positive for P-glycoprotein. These results indicate that TO73 preferentially reacts with leukemic cells resistant to chemotherapy and may be a new marker for refractory leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗