Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 145 records · Page 8Linked to original sources

PubMed1996

[Clinical value of carbohydrate antigens, sialyl Lewis-x and sialyl Lewis-a in gastrointestinal cancer].

To evaluate clinical importance of the expression of sialyl Lewis-X (sLe(x)) and sialyl Lewis-a antigen (sLe(a)) in gastrointestinal cancers, we examined immunohistochemically expression of the two antigens in esophageal, gastric, colorectal, and pancreatic cancer. Expression of sLe(x) and sLe(a) were associated with several clinicopathologic features which reflect tumor aggressiveness in esophageal, gastric and colorectal cancer, but not in pancreatic cancer. In esophageal and colorectal cancer, survival rate of the patients with sLe(x) positive tumors was significantly poorer than that of the patients with sLe(x) negative tumors, while in gastric cancer that with sLe(a) positive tumors was significantly poorer than that with sLe(a) negative. Cox's multivariate analysis revealed that sLe(x) expression status was one of the significant discriminants of prognosis in colorectal cancer patients and sLe(a) status in gastric cancer patients. These results suggest that sLe(x) and sLe(a) expression could be involved in aggressiveness of gastrointestinal cancer and might prove to be a potent marker for prognosis in patients with gastric cancer and colorectal cancer.

Adult↗

PubMed1996

[Comparative study of the combined effect of HCFU and dipyridamole (DP) in colorectal carcinoma--TS inhibition rate. Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma].

In the forty-seven medical centers in the Kinki district, a comparative trial was conducted to investigate the enhancement of the efficacy of HCEU due to dipyridamol (DP), which is a biochemical modulator in patients with colorectal cancer who have had a curative resection. The trial consisted of two comparative groups: one group (Group A) received HCFU only for five days before operation and for two years from the second week, and the other group (Group B) was given HCFU + DP for the same trial period as Group A. The total number of patients collected was 653 (Group A: 327 patients; Group B: 326 patients) during the two-year trial period from October, 1991. Thymidylate Synthetase (TS) activity in the primary lesions, which is an index of proximity effect, was measured, and the TS inhibition rate (TSIR) was calculated from the activities. The results showed that the TSIR in the primary lesions for the HCFU + DP group (Group B: 0.33) was significantly higher than that of the HCFU group (Group A: 0.27) (p = 0.0006). There was no increase in the side effects of HCFU due to combined administration with DP. From the above results, the therapy with HCFU + DP is expected to be useful for patients with colorectal cancer who have undergone curative resection.

Adult↗

PubMed1996

[Adjuvant chemotherapy for advanced gastric cancer].

For recent 40 years, many authors reported the results of adjuvant chemotherapy for advanced gastric cancer including 5-fluorouracil, uracil and tegafur, mitomycin C, cytosine arabinoside. OK-432 adriamycin, methotrexate, and cis-pltatin in solitary use of combinations. It is difficult to find a standard effective adjuvant chemotherapy for advanced gastric cancer in these reports. The reasons of this unclearness were as follows; (1) In phase III studies, surgery alone was not a control group in some reports. (2) The number of patients was too small to evaluate statistically. (3) Inter-institutional differences had important roles in the results of multicenter study in the other studies. For the future plans on adjuvant chemotherapy, it is important to make a simple designed protocol, and perform it as a multicenter study including institutions with minimum inter-institutional differences.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

[Diffuse tracheobronchial amyloidosis with airflow limitation and repeated pneumonias].

A 67-year-old man was first admitted to our hospital complaining of a productive cough, and repeated episodes of pneumonia in different sites. Physical examination revealed expiratory wheezing and airflow limitation wlas documented with lung function tests. A chest X-ray film showed patchy pneumonic infiltrates. Chest computed tomography revealed a marked thickening of the tracheal and bronchial wall with linear calcification. Fiberoptic bronchoscopy revealed a diffuse infiltrative process in the tracheobronchial tree, which uniformly reduced the bronchial lumen. Bronchial biopsy specimens showed amyloid deposits with focal calcification, which was confirmed by Congo red and Dylon staining. Extensive examinations including rectal biopsy were negatie for systemic amyloidosis. We suggest that diffuse tracheobronchial amyloidosis should be included in the differential diagnosis of repeated pulmonary infections with airflow obstruction.

Aged↗

PubMed1996

[Three cases of tuberculous mediastinal lymphadenitis].

Mediastinal lymph node involvement is uncommon in intrathoracic tuberculosis. We report three cases of this disease, each of which had a different clinical course. Chest CT scans showed preferential involvement of right paratracheal nodes, central areas of relatively low density with peripheral rim enhancement after injection of contrast medium. Specimens obtained by mediastinoscopy and fiberoptic bronchoscopy revealed acid-fast bacilli in all cases. In view of its relative frequency, tuberculous mediastinal lymphadenitis in adults must be distinguished from other causes of mediastinal masses.

Adult↗

PubMed1996

[Hepatic resection with "wrapping therapy" for advanced hepatocellular carcinoma uncontrolled by arterial embolization].

We report a 70-year-old male patient who had successful hepatic resection with "Wrapping therapy" for advanced hepatocellular carcinoma (HCC) uncontrolled by arterial embolization. His laboratory tests were as follows: Alb: 4.7 (g/dl), T. Bil:0.9 (mg/dl), ICG R15:26.8 (%), PT: > 100%, AFP:33 (ng/ml), HCV-Ab:(-), HBs-Ag:(-). Hepatic angiogram showed a 20 cm sized tumor in the left lobe and many large and small tumors in the right lobe. He received chemoembolization (TAE) five times during seven months. At the time of the fifth hepatic angiogram, TAE was assessed as ineffective because of the resulting collateral feeding arteries. Thus, he underwent left lobectomy, partial resection of the right lobe, and partial "Wrapping therapy" for the regions including foci supplied with parasitic branch. Afterwards, he had TAE two times. One year and five months after the procedure, he is still alive without signs of recurrence.

Aged↗

PubMed1996

[A case of successful management of advanced cholangiocellular carcinoma by repeated hepatic resection].

A 50-year-old woman with advanced cholangiocellular carcinoma (CCC) underwent extended left hepatectomy and catheterization into the hepatic artery. Following the procedure, intra-arterial infusion chemotherapy of the fluorouracil (5-FU) was performed. This chemotherapy was given 13 times at 2,500 mg for 10 months, so the total dose of 5-FU was 32.5 g. About two years after the operation, the patient underwent hepatic resection again for solitary recurrence of CCC. The prognosis of CCC is very poor. Aggressive surgical resection may be the only method to assure a good outcome. However, the survival rate after curative resection has been low. Adjuvant hepatic arterial infusion chemotherapy after surgery may be effective for a good prognosis.

Antimetabolites, Antineoplastic↗

PubMed1996

[A case of non-resectable pancreatic cancer surviving more than 4 years by intra-arterial infusion chemotherapy with angiotensin-II].

This is a report of a 62-year-old woman whose non-resectable pancreatic cancer had been treated effectively by a new method of intra-arterial regional chemotherapy for more than 4 years. A catheter was placed into the celiac artery during laparotomy, and an intra -arterial chemotherapy (methotrexate (50 mg) and Angiotensin-II (AT-II, 5 micrograms)) has been repeated every other week (108 times) in addition to the external beam therapy (50 Gy). Both pain relief and "partial response" in the size of tumor have been obtained, with no hepatic metastasis or adverse effect. She died of brain metastasis at 51 postoperative months. Autopsy revealed that the pancreatic tumor was mostly replaced by fibrous connective tissues. Scintigraphic study indicated that the intra-arterial infusion of AT-II increased the blood flow in the tumor but decreased it in the surrounding non-cancerous tissues. This seemed to explain the effective loco-regional control in the present case.

Angiotensin II↗

PubMed1996

[Adjuvant therapies in combination with pancreatectomy for carcinoma of the pancreas].

In the treatment of adenocarcinoma of the pancreas, surgical resection is the only curative strategy. However, the long-term survival rate after pancreatectomy remains poor, and most patients died of loco-regional and/or hepatic recurrence. Thus, we should perform effective adjuvant therapies in combination with surgery, in order to completely prevent these two types of cancer relapse. The present article is designed to introduce the recent reports on the adjuvant chemo-and/or radio-therapies for this cancer. As for loco-regional control, extended pancreatectomy plus chemoradiation seems to be most promising, and preoperative chemoradiation will be more popular in the near future. In order to decrease hepatic metastasis, our "2-channel chemotherapy", a continuous infusion of 5-FU via both hepatic artery and portal vein, is very promising. If postoperative survival is improved by combining these two types of regional therapy, the role of pancreatectomy will be enlarged and more widely understood in the near future.

Adenocarcinoma↗

PubMed1996

Macrophagic cells outgrowth from normal rat glomerular culture: possible metaplastic change from podocytes.

One representative of a number of severe lesions that occur outside the glomerular capillaries and involve podocytes is crescentic glomerulonephritis. The question of whether the crescent-forming cells are derived from glomerular epithelial cells or monocytes/macrophages is highly controversial and has not yet been clarified. To investigate the pathophysiology of podocytes in crescentic glomerulonephritis, we attempted to establish methods for culturing cells confirmed to be derived from podocytes, focusing particularly on the relationship between podocytes and macrophages. Nonadherent cells of unknown origin that grew from normal rat isolated glomerular cultures increased in number, reaching a total of 3.5 x 10(5)/ml on Day 11. They showed several characteristics of macrophages, the expression of specific antigens and enzymes, morphology, and production of H2O2. They expressed Fx1A but lacked the expressions of Thy1.1 or factor VIII. A morphologic kinetic study on Days 3 to 11 of culture showed that the cells with foot processes on the glomerular basement membrane changed into macrophagic cells (MC) and migrated from the glomeruli. Immunofluorescence double staining indicated that the cells that migrated from the glomerular surface on Day 8 were both anti-podocalyxin- and ED-1-positive. Furthermore, immunoelectron microscopy revealed that the ED-1-positive cells were located on the glomerular basement membrane. Pretreatment with anti-macrophages and -Thy1.1 antibodies, both with complement, did not reduce the number of MC, whereas pretreatment with puromycin aminonucleoside predominantly reduced the number of MC. A predominant decrease in the number of glomerular macrophages by gamma-irradiation did not result in a reduction of the number of MC. MC derived from glomerular cultures of bone marrow chimeric rats expressed the la antigen originated from recipient, which indicates that MC is not derived from bone marrow cells. Macrophage colony-stimulating factor accelerated the speed of the change into MC, and granulocyte-macrophage colony-stimulating factor dramatically enhanced its degree with increase of cell number on Day 8. We concluded that podocytes change into MC in normal rat glomerular culture and that the change is enhanced by colony-stimulating factors. The results provide a completely new insight into the origin of crescent-forming cells.

Animals↗

PubMed1996

[Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant].

Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

Administration, Oral↗

PubMed1995

Supportive cellular elements for hepatic T cell differentiation: T cells expressing intermediate levels of the T cell receptor are cytotoxic against syngeneic hepatoma, and are lost after hepatocyte damage.

Extrathymic T cells exist in the liver and are often seen in close contact with Kupffer cells in the hepatic sinusoids. Since selective depletion of Kupffer cells has become possible by using liposome-encapsulated clodronate, it was investigated whether elimination of Kupffer cells influences the level of extrathymic T cells in the liver. Extrathymic T cells were identified as interleukin-2 receptor beta-chain (IL-2R beta) intermediate TCR (TCRint) cells by two-color staining for CD3 or T cell receptor (TCR) and IL-2R beta. The elimination of Kupffer cells did not significantly affect levels of TCRint cells up to 7 days after treatment. We then examined monocyte colony stimulating factor (M-CSF)-deficient op/op mice (low levels of Kupffer cells). Extrathymic T cells both in the liver and spleen of these mice were detected at a level comparable to that of control mice. Since extrathymic T cells in the liver are sometimes located in the parenchymal space, the relationship between extrathymic T cells and hepatocytes was then examined. Electron microscopy revealed that some hepatic T cells adhered directly to hepatocytes. When hepatocytes were damaged by a single injection of CCl4, hepatocyte death and subsequent hepatic fibrosis were induced. Beginning 3 days after injection, CD3int cells, but not other type of cells, decreased prominently. Purified CD3int cells, as well as whole lymphocytes in the liver, were cytotoxic against syngeneic hepatoma. In parallel with the above-mentioned hepatic damage, the cytotoxic activity of lymphocytes against such targets was impaired in the liver. These results suggest that extra-thymic generation of TCRint cells and their acquisition of cytotoxic function are relatively independent of Kupffer cells, but are dependent on hepatocytes.

Animals↗

PubMed1995

Randomized study with mitomycin C + 5-fluorouracil+cytosine arabinoside (MFC)+5-fluorouracil, MFC+tegafur and uracil (UFT), and MF+UFT in advanced gastric cancer: interinstitutional differences in a multicenter study in Japan.

In a phase III randomized trial of adjuvant chemotherapy for gastric cancer, interinstitutional differences were analyzed. A trial of three regimens: mitomycin C, 5-fluorouracil(5-FU) and CA (MFC) + continuous oral 5-FU (Group C); MFC + continuous oral UFT(tegafur and uracil) (Group B); and MF + UFT (Group C) after operation was conducted in 466 patients with gastric cancer (stage II and III) at four hospitals in Japan (CIH, CAD, ACC and NCC). Patients were stratified by the institution, stage, and tumor size (8 cm ><). The 5-year survival rates were in the order of Group A (79.0%) > B (70.0%) > C (61.0%) (P = 0.1228) in total, A (95.0%) > B (80.0%) > C (58.0%) (P < 0.05) at CAD (82 patients), A > C > B at CIH (215), C > A > B at ACC (95), and B > A > C at NCC (78). The survival rate of patients with S2(serosal exposure), 8 cm < and N0-1 cancer was higher at CIH than at the other institutions. The interinstitutional differences in patient characteristics and surgical technique were more powerful than the differences among the three groups.

Administration, Oral↗

PubMed1995

Ultrastructural and time-lapse observations of intraepithelial lymphocytes in the small intestine of the guinea pig: their possible role in the removal of effete enterocytes.

In previous ultrastructural studies we have shown that at the tip of intestinal villi in guinea pigs, effete enterocytes are separated into two portions: a thin apical cytoplasm to be exfoliated into the lumen and a major basal portion to be ingested by lamina propria macrophages. During this process, intraepithelially disposed, large granular lymphocytes interdigitate with enterocytes in a complex manner. In the present study, the relation between the enterocytes and the lymphocytes in the villous epithelium of the guinea pig small intestine is described by use of transmission and scanning electron microscopy in an attempt to visualize the roles and activities of the lymphocytes more clearly. The lymphocytes project numerous pointed processes into effete enterocytes, even piercing them. Enterocytes are deeply indented or perforated, probably as a result of the encroaching lymphocyte processes. Some enterocytes are separated into apical and basal portions by numerous large excavations in the cytoplasm. These findings indicate that repeated perforating penetration of the lymphocytes induces cell cleavage. Supporting this supposition, our microcinematographic observations demonstrate the alternate protrusion and withdrawal of processes of lymphocytes. The processes advance with a pointed end, and subsequently, retract with a rounded end in a cycle of 8-18 seconds.

Animals↗

PubMed1995

Regional differences of CGRP-immunoreactive nerve fibers in nasal epithelium of the rat.

The regional distribution of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the epithelium throughout the nasal cavity was determined using semiserial cryostat sections and whole mount preparations. Both respiratory and olfactory epithelia displayed, in their basal portion, an extensive nerve plexus projecting beaded nerve fibers toward the luminal surface. However, the density of the intraepithelial CGRP nerve fibers conspicuously varied according to regions. They were abundant on the septal mucosa, the ventromedial side of the nasoturbinates and the dorsal surface of the maxilloturbinates, while less numerous on the lateral side of the naso- and maxilloturbinates and on the lateral nasal wall. Another difference in the regional distribution of nerves was recognized between the anterior and posterior portions of the respiratory area: the anterior portion received a denser supply of intraepithelial CGRP fibers than the posterior portion. Characteristically, the transepithelial CGRP-immunoreactive nerve fibers were densest on the anteroventral aspect of the nasoturbinates and on the anterodorsal surface of the maxilloturbinates. Some of them appeared to penetrate through the epithelium to come into contact with the lumen of the nasal cavity. These results suggest that the CGRP fibers in the epithelium display a region-specific distribution, apparently disposed more densely over the areas which are more directly exposed to inhaled air, possibly that containing irritants and toxicants.

Animals↗

PubMed1995

The involvement of macrophages and lymphocytes in the apoptosis of enterocytes.

Epithelial cells of the gut are characterized by rapid, constant cell renewal. The death of epithelial cells at the villus tips occurs so regularly that it must be regarded as a well-controlled cell death, designated as apoptosis. However, only limited information has been available on the mechanism of this phenomenon, including the disposal of the effete cells. In the small intestine of the guinea pig and monkey, macrophages are densely aggregated at the lamina propria of the villus tips and vigorously engaged in the phagocytosis of effete epithelial cells. Intraepithelial lymphocytes possessing cytoplasmic granules, possibly intense in cytotoxicity, are topographically associated with the dying enterocytes, suggesting lymphocyte-mediated killing. After the engulfing of apoptotic enterocytes is left within the epithelium, maintaining the epithelial barrier until it is pinched off by the pushing of surrounding enterocytes. In the rat and mouse, on the other hand, effete enterocytes are exfoliated as a whole from the villus tips into the gut lumen. Macrophages, also numerous at the villus tips in these species, are less intense in phagocytotic activity. At the shoulder region of the villus, subepithelial macrophages extend thick processes deep into the epithelium; the processes appear to push out some enterocytes with typical apoptotic signs into the gut lumen. Lamina propria macrophages in the rat and mouse do not engulf enterocytes, but are believed to be involved in the induction of their apoptosis. The species difference in the mechanism of the apoptosis of enterocytes provides clues for understanding apoptosis.

Animals↗

PubMed1995

The fate of effete epithelial cells at the villus tips of the human small intestine.

Until recently, little has been known about the morphological features of dying enterocytes at the villus tips of the human small intestine. The present study aimed to show the exfoliating processes of effete enterocytes at the villus tips. Cellular elements of the duodenal lumen and jejunal tissue in humans were fixed and processed for DNA nick end labeling (TUNEL), and transmission and scanning electron microscopy (TEM and SEM). Most cellular elements in the duodenal lumen were enterocytes having TUNEL-positive nuclei. By SEM, protruding enterocytes were discerned at the villus tips. Using the SEM samples embedded in epoxy resin, protruding enterocytes were observed at the villus tips by TEM; they were shrunk by forming numerous clear and autophagic vacuoles, took dome-like profiles, and possessed nuclei with chromatin condensation. The intercellular spaces beneath these protruding or effete enterocytes were often occupied by large lymphocytes. By TUNEL reaction, positive stainings appeared in the epithelium not only at the tip of the villi but also around the site. The results suggest that effete enterocytes at the villus tips of human small intertine are first shrunk by forming clear and autophagic vacuoles, and showed that their nuclei exhibit chromatin condensation immediately before being exfoliated into the lumen.

Adult↗

PubMed1995

Multinucleated giant cells undergoing apoptosis in experimental autoimmune myocarditis.

This study used an experimentally induced myocarditis model in rats to demonstrate the formation and fate of multinucleated giant cells which are known to occur in different kinds of inflammatory lesions. Multinucleated giant cells were frequently recognized in the inflammatory foci, being intermingled with numerous ED1-positive inflammatory macrophages rich in phagosomes. The giant cells reacted with the ED1 antibody but not with ED2, and ultrastructurally resembled the inflammatory macrophages. Multinucleated giant cells possessing less than 5 nuclei in an ultrathin section were rich in phagosomes, whereas those with more nuclei contained numerous lipid droplets and only few phagosomes in their cytoplasm. Light microscopic observation of hematoxylin-eosin stained sections revealed that some multinucleated giant cells displayed variously sized dark bodies which likely corresponded to condensed and fragmented nuclear chromatin. Such multinucleated giant cells were positively stained with the TUNEL method. Under the electron microscope, all nuclei in one multinucleated giant cell showed an eccentric mass of homogeneously condensed chromatin. These observations suggest that multinucleated giant cells are formed by aggregation and also likely by fusion of inflammatory macrophages; gradually loosing the phagocytotic activity characteristic of the latter cells, they then die by apoptosis.

Animals↗