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Biomedical subjects

T Umeda

Publications and source records attributed to T Umeda.

At least 109 records · Page 6Linked to original sources

Direct tumor growth suppressive effect of melanoidin extracted from immunomodulator-PSK.

Melanoidin, which belongs to the melanin group of molecules, was extracted from the polysaccharide biological response modifier PSK. Melanoidin was cultured together with HCT-15 cells derived from human colon cancer and with AGS cells derived from human gastric carcinoma. After four days of culture, cell count was compared with that of the control cells. Significant suppression was observed, that is, 50% suppression was shown at concentrations of melanoidin between 200 and 100 micrograms/ml. A histogram generated by flow cytometry showed elevation of the tetraploid peak and of that between diploid and tetraploid peaks, suggesting blockage of S phase and G2 to M phase of the cell cycle. Thus, melanoidins contained in the immunomodulator PSK revealed to have a direct tumor cell growth inhibitory effect.

Adjuvants, Immunologic↗

Tumor cell growth-inhibiting effect of melanoidins extracted from miso and soy sauce

Melanoidins, a group of plant-produced melanins, were extracted from miso and shoyu (soy sauce), which are products of soybeans and widely consumed as food in oriental countries. The molecular weight of these melanoidins was approximately 5600 as revealed by Sepharose CL-4B column chromatography. The melanoidins were cultured together with HCT-15 cells derived from human colon carcinoma and AGS cells derived from human gastric carcinoma. Significant cell growth suppression was observed by incubating the cells with these melanoidins. The 50% growth suppression dose ranged between 100 micrograms/ml and 25 micrograms/ml, that is, between 2 x 10(-5) mM/ml and 0.5 x 10(-5) mM/ml. Flow cytometric analysis suggested that these melanoidins blocked the S phase and G2 to M phase of the cell cycle.

Journal Article↗

Suppression of growth of cultured malignant cells by allomelanins, plant-produced melanins.

Allomelanins, which belong to the melanins produced by higher plants and fungi, were studied with respect to their growth suppressive effects on cultured HCT-15 cells derived from human intestinal carcinoma and Meth/A cells derived from a Balb/C mouse lymphoma. Allomelanins were extracted from black soy beans and black sesame seeds with 0.2% NaOH in water. Proteins bonded to the allomelanins were removed by boiling the extracts for 20 hours in 30% NaOH. Although native allomelanins conjugated with protein did not suppress the growth of the cells, protein-free allomelanins did suppress it. That is, 50% suppression of HCT- 15 cell growth was found at a concentration between 100 and 200 micrograms/ml of the melanin prepared from the black soy beans, and between 25 and 100 micrograms/ml of that from the sesame seeds. For Meth/A cells, 50% suppression by allomelanin from the black beans was approximately 100 micrograms/ml; and that by the allomelanin preparation from sesame seeds, between 25 and 100 micrograms/ml. Thus, protein-free allomelanins seemingly suppress cultured mammalian and animal tumor cells.

Animals↗

Coxalgia as the initial symptom in Hodgkin's disease: a case report.

Primary Hodgkin's disease in the bone is extremely rare. We report the case of a 41-year-old woman with Hodgkin's disease, who had complained of left coxalgia 17 months prior to nodal involvement becoming evident clinically. She received combination chemotherapy with doxorubicin, bleomycin, vincristine and dacarbazine as well as radiotherapy to the pelvic lesion. Although the lymphadenopathy responded well to this treatment, the bone lesion was never in remission. The large mass of the bone lesion and its pelvic origin may explain the poor response to the cytotoxic therapies this patient received. The 22 cases reviewed showed that: 1, bony pain was the most frequent initial symptom; 2, nodal disease appeared in their clinical course in most cases; 3, the bones most commonly involved were pelvis, femur or tibia, and spine.

Adult↗

Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.

Adult↗

Neuromuscular target recognition by a homophilic interaction of connectin cell adhesion molecules in Drosophila.

Drosophila Connectin (CON) is a cell surface protein of the leucine-rich repeat family. During the formation of neuromuscular connectivity, CON is expressed on the surface of a subset of embryonic muscles and on the growth cones and axons of the motoneurons that innervate these muscles, including primarily SNa motoneurons and their synaptic targets (lateral muscles). In vitro, CON can mediate homophilic cell adhesion. In this study, we generated transgenic lines that ectopically expressed CON on all muscles. In the transformant embryos and larvae, SNa motoneurons often inappropriately innervated a neighboring non-target muscle (muscle 12) that ectopically expressed CON. Furthermore, the ectopic synapse formation was dependent on the endogenous CON expression on the SNa motoneurons. These results show that CON can function as an attractive and homophilic target recognition molecule in vivo.

Animals↗

Relationship between weight change in young adulthood and the risk of NIDDM. The Sotetsu Study.

OBJECTIVE: To investigate the independent effect of weight change in young adulthood on the risk of prevalent NIDDM among middle-aged Japanese men. RESEARCH DESIGN AND METHODS: A case-control study was carried out in 895 male employees aged > or = 30 years of a railway company located in the vicinity of Tokyo. Adjusted odds ratios (ORs) were calculated for prevalent diabetes in each category of weight change (obtained from subjects' medical records) in young adulthood and adulthood. Adjustment for current age, initial BMI, and weight change in each age stratum was performed by the Mantel-Haenszel method or multiple logistic regression analysis. RESULTS: Weight change between 20 years of age and the age at maximum weight was not associated with the risk of NIDDM. Weight gain between 20 and 25 years of age was significantly and positively associated with the risk of NIDDM (OR 3.87 for gains > or = 10.0 kg, 2.53 for gains of 5.0-9.9%, and 3.73 for gains > or = 10.0%). On the other hand, moderate weight gain after 30 years of age was significantly inversely associated with NIDDM (OR 0.44 for gains of 5.0-9.9 kg, 0.15 for gains of 10.0-19.9%, and 0.38 for gains of 20.0-29.9%). CONCLUSIONS: Extreme weight gain between 20 and 25 years of age is a significant predictor of NIDDM, independent of current age, BMI at 20 years of age, and weight change within other age strata.

Adult↗

[Cost effectiveness of image diagnosis].

First, annual cost of electronic filing of medical images were calculated and compared with that of film storage in two hospitals under different conditions. Storage of medical images using a pixel size of 100 microns x 100 microns and 2-byte depth on the 130 mm, 650 MB magneto-optical disks costs with four times as much as the cost for film storage. However, 175 microns x 175 microns 12 bits combined with implementation of lossless compression would reduce the cost to a level equal to that for films storage. Doubled or tripled densities of MOD will improve the cost ever further. Second, the effectiveness of Hospital Information System/Radiological Information System (HIS/RIS) was evaluated. Examination time, film delivery time and the total turn-around time was markedly shortened by more than 23 hours on average. Our measurement method employing IC cards in pre-post HIS/RIS/PACS procedures is generally applicable to other hospitals. Third, to determine the optimal method of maximizing the efficacy of diagnostic imaging, 260 questionnaires were sent to the staff of 13 university hospitals. Every situation was described by both a radiologist and the physician who ordered the examination and received the reports and images. The level of technical efficacy and diagnostic accuracy of radiology strongly influenced the diagnostic thought processes of the physician.

Cost-Benefit Analysis↗

Interferon-gamma differentially regulates CD80 (B7-1) and CD86 (B7-2/B70) expression on human Langerhans cells.

CD80 (B7-1) and CD86 (B7-2/B70) have recently been identified in cultured human Langerhans cells (LCs), although their role and regulatory properties remain unclear. We present our comparison of the expression of the molecules, mRNAs and the function between CD80 and CD86 in human LCs treated by interferon gamma (IFN-gamma). We examined the regulatory properties of CD80 and CD86 expression in human LCs pretreated with IFN-gamma. Flow cytometric analysis indicated that the mean fluorescence intensity of CD86 but not CD80 was enhanced. However, the percentage modulation of both CD80 and CD86 positive cells were significantly up-regulated in a dose-dependent manner, after 48-h culturing with IFN-gamma. The regulatory properties of CD80 and CD86 mRNA expressions in human LC were studied using polymerase chain reaction methods. We found that both CD80 and CD86 mRNA of enriched LCs following IFN-gamma pretreatment for 12 h were higher than those without pretreatment. We have demonstrated that the primary allogeneic mixed epidermal cell-lymphocyte reaction induced by human LCs treated by IFN-gamma increased in a dose-dependent manner. There was a 61.5% inhibition by anti-CD86 monoclonal antibody and a 32.5% inhibition by anti-CD80 monoclonal antibody. These data indicate that the CD80 and CD86 expression of human LCs may be differently regulated by IFN-gamma.

Antigens, CD↗

Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis.

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4), CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 nor CD80 was detected on keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n = 7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n = 8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely inhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.

Animals↗

Expression of cathepsin D and B in invasion and metastasis of squamous cell carcinoma.

To determine the involvement of proteinases with hydrolytic activity towards extracellular matrix and basement membrane, in invasion and metastasis of tumour cells, the expression of cathepsin D, an aspartic proteinase, and cathepsin B, a cysteine proteinase, was studied. Formalin-fixed paraffin-embedded specimens from 13 patients who had squamous cell carcinomas (SCC) with local recurrence, skin and/or lymph node metastasis were examined. Cathepsin D stained intensely as a granular pattern (mature enzyme) in tumour cells of 69% of primary lesions and all the secondary lesions of the patients with SCC. Cathepsin B stained more intensely in SCC cells of all of the primary and secondary lesions than in normal epidermis; staining patterns were almost diffuse (procathepsin B). Granular and diffuse patterns (mature enzyme of cathepsin D and procathepsin B, respectively) appeared in the outer and inner parts of tumour islands, respectively. The presence of the active mature form of cathepsin D and procathepsin B in metastatic skin lesions of SCC was confirmed by Western blotting analysis. The presence and localization of the active mature form of cathepsin D suggests that activated cathepsin D may be involved in the invasion and metastasis of SCC.

Blotting, Western↗

[The effects of high-dose ifosfamide in the treatment of bone and soft tissue sarcomas].

From January 1990 to December 1995 we treated 35 patients (pts) with bone and soft tissue sarcoma with ifosfamide (IFM). Sixteen patients had measurable metastatic pulmonary lesion and 9 had primary lesion. Histology of the tumor included osteosarcoma in 13 pts, Ewing sarcoma in 5 pts, malignant fibrous histiocytoma of bone in 2 pts, synovial sarcoma in 7pts, primitive neuroectodermal tumor in 2 pts, and other in 7 pts. The IFM at the dose of 12-18g/m2 (mean 15. 4g/m2) for 5 to 8 days continuous infusion was administered to patients in each treatment course. The uroprotector, mesna, was also given concomitantly in 60-100% dose of IFM. Eighteen pts received one course of IFM treatment. Other pts received 2 to 8 courses of IFM treatment at three to four week intervals. The overall response rate was 40% (PR in 14 pts, NC in 18 pts, and PD in 3 pts). The response rate of 13 pts with osteosarcoma was 54% (PR in 7 pts) and 30% in 15 pts with soft tissue sarcoma (PR in 5 pts).

Adolescent↗

[The risk of palliative operation for bone metastasis].

Palliative operations for various bone metastases are being performed more frequently than before with the improvement of surgical technique and the development of new instruments. However, anesthesia in advanced cancer patients who are under palliative care accompanies inherent risks which are uncommon in general orthopaedic populations. Thus, we made a retrospective analysis of the medical records of 59 patients scheduled for palliative operation against metastatic bone lesions during the last 4 years. The survey revealed 5 cases of perioperative lethal events. Two of them died preoperatively from the hepatic failure and unexpected cerebral tumor embolism. An intraoperative cardiac arrest secondary to pulmonary embolism occurred in a patient during intramedullary nailing. There was a patient who developed disseminated intravascular coagulation and acute renal failure after posterior fixation of the lumbar vertebrae. The remaining one patient with superior vena cava syndrome developed life-threatening airway obstruction during general anesthesia with endotracheal intubation. We conclude that the exact evaluation of the patient's condition and the careful management of vital organ functions are mandatory during the perioperative period. In this regard, the anesthesiologists should be involved not only in the intraoperative anesthetic management but also in the perioperative care of the patients with bone metastasis.

Adult↗

Immunohistochemical analysis of the poorly differentiated stomach adenocarcinoma with medullary growth pattern.

Poorly differentiated gastric adenocarcinoma with medullary features (poor medullary) is distinguished by a propensity for hepatic metastasis. To classify it antigenically, we compared it to poorly differentiated adenocarcinoma with scirrhous growth pattern (poor scirrhous), well and moderately differentiated adenocarcinoma (differentiated adenocarcinoma), and normal gastric mucosa (foveolar and deep epithelium) using immunohistochemistry with antibodies against CEA, AFP, NSE, and Lewis-type antigens. Lewis(a) antigen was significantly associated with differentiated adenocarcinoma and foveolar epithelium, although Lewis(x) antigen was significantly expressed in poor medullary, poor scirrhous, and deep gland epithelium. From the viewpoint of expression of Lewis(a), there was no significant differentiation between poor medullary and differentiated adenocarcinoma, but it was definite between poor scirrhous and differentiated adenocarcinoma. Therefore, we conclude that in antigenic expression, poor medullary carcinoma is allied with differentiated adenocarcinoma rather than poorly differentiated scirrhous carcinoma.

Adenocarcinoma↗

A new model for pancreaticobiliary maljunction without bile duct dilatation: demonstration of cell proliferation in the gallbladder epithelium.

Patients with pancreaticobiliary maljunction without bile duct dilatation (PBMWBDD) develop gallbladder carcinoma frequently. No models of PBMWBDD exist, and no previous studies have clearly demonstrated changes in the gallbladder relating to carcinogenesis. We, therefore, examined the cell kinetics of the gallbladder epithelium in a new experimental model of PBMWBDD. A cat model was produced by performing choledocho-pancreatic side-to-side ductal anastomosis in nine animals. Five cats, in which the choledocho-pancreatic ducts were exposed only, served as controls. After 6 months, the gallbladders of these cats were removed and stained with anti-proliferating cell nuclear antigen (PCNA) antibody (PC10, Dako). The labeling index (LI) was determined from the percentage of positive nuclei in three microscopic fields. The diameter of the common bile duct was not different between the models and the controls. In the models, the number of PCNA positive cells was significantly increased. The mean (+/- standard deviation) PCNA LI was 28.1 +/- 12.2% in the models and 4.3 +/- 1.6% in the controls (P < 0.01). These studies clearly indicate that this model is suitable for studying PBMWBDD and that PBMWBDD has a prominent proliferating effect on the gallbladder epithelium which may play an important role in gallbladder carcinogenesis.

Amylases↗