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Biomedical subjects

Y Ogata

Publications and source records attributed to Y Ogata.

At least 163 records · Page 9Linked to original sources

Clinicopathologic characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer.

PURPOSE: This study was designed to clarify the characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer. METHODS: A retrospective chart review was performed. RESULTS: The latent period was a mean of 20.5 years. The most common site was in the rectum (16/32). Mucin-producing carcinoma was observed in 53.1 percent, with an especially high rate of 75 percent in the rectum. Histologic radiation damage was also demonstrated at a high rate of 64.3 percent. CONCLUSIONS: It was difficult to judge from clinicopathologic findings whether large bowel cancer developed with relation to radiation effect. We emphasize, however, that the characteristics are different from ordinary large bowel cancer. Particular consideration should be given to the high incidence of mucin-producing carcinoma.

Adenocarcinoma, Mucinous↗

Presence of endogenous chemotactic factors for periodontal ligament cells in bovine cementum and bone.

When bovine cementum and bone were subjected to sequential dissociative extraction first with 4 M guanidine HCl ('G' extract) and then with 4 M guanidine HCl/0.5 M EDTA ('E' extract), high chemotactic activities for periodontal ligament cells were detected in the 'G' extracts using modified Boyden chambers. The chemotactic activities in both tissue extracts were destroyed by trypsin and heat. However, the activities in bone extracts were more heat-stable than those in cementum. When both tissue extracts were separated into bound and unbound fractions by DEAE-Sephacel ion-exchange chromatography, the chemotactic activities in cementum were detected in the unbound fractions, and those in bone in the bound fractions, which were eluted by 1 M NaCl. These results suggest that cementum and bone contain different chemotactic protein factors for periodontal ligament cells.

Animals↗

Cellular localization of matrix metalloproteinases in the abdominal aortic aneurysm wall.

PURPOSE: This study explores the source(s) of the matrix-degrading proteinases, matrix metalloproteinase 1 (MMP-1; interstitial collagenase), matrix metalloproteinase 3 (MMP-3; stromelysin 1), and matrix metalloproteinase 9 (MMP-9; gelatinase B), previously implicated in abdominal aortic aneurysm (AAA) development. The possible involvement of the plasmin cascade in the activation of these proteinases was also explored by examining the presence of the urokinase-type plasminogen activator (uPA) in aneurysm wall. METHODS: Immunohistochemical techniques were used to detect the presence of MMP-1, MMP-3 and MMP-9 proteins and uPA in fixed, paraffin-embedded tissue sections from AAA (n = 10) and control (n = 2) aortas. RESULTS: The MMP-9 protein was localized to mononuclear cells in the AAA wall. Dual-labeling techniques confirmed the identity of these cells as macrophages. The MMP-3 protein and uPA were also detected primarily in the macrophage-like mononuclear cells infiltrating the aneurysmal aorta. Immunoreactive material to MMP-1 was demonstrated in mesenchymal cells of the AAA wall suggesting alternative expression and delivery of this enzyme in AAA. CONCLUSIONS: This work establishes the role of macrophages in the delivery, expression, and possible activation of matrix destructive proteinases during AAA pathogenesis and suggests a role for the activation of MMPs in the progression of the disease.

Antibodies, Monoclonal↗

Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.

A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteolytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease.

Aorta, Abdominal↗

Effects of Z-300, a new histamine H2-receptor antagonist, on mucin biosynthesis in rat gastric mucosa.

We examined the effects of Z-300 (N-[3-[3- (piperidinomethyl)phenoxy]propyl]-2-(2-hydroxy-ethyl-1-thio)acetam ido.2- (4-hydroxy benzoyl)benzoate), a newly-synthesized selective histamine H2-receptor antagonist, on mucin in rat gastric mucosa. Deep corpus mucin content increased significantly to 127% of the control after the administration of 30 mg/kg of Z-300, whereas that in the antral mucosa did not increase. The addition of Z-300 significantly increased [3H]-labeled mucin in the corpus region. In the antrum, biosynthetic activity showed no significant change by 10(-8)-10(-5) M of Z-300. These results suggest that Z-300 not only inhibits acid secretion but may also promote gastric mucus metabolism in the corpus region.

Acetamides↗

Characteristics of neo red cells, their function and safety: in vivo studies.

A new type of artificial oxygen carriers, the Neo Red Cells (NRCs) have been developed and investigated for oxygen transporting efficiency and safety in experimental animals. Stroma free hemoglobin from outdated human red blood cells together with inositol hexaphosphate as an allosteric effector under sterile, pyrogen free condition were encapsulated in liposomes and then were coated with polyethylene glycol bond to hydrogenated soy phosphatidylethanolamine as a surface modifier to prevent aggregation of NRCs in plasma. The efficiency of the NRCs in tissue oxygenation was studied in rabbits which were made severely anemic by drawing 85% of their blood and immediately replacing it with NRC solution. The animals, all recovered to pre-anemic conditions within 6-8 hr and lived normally until being sacrificed, 6 months after the exchange transfusion. The circulation half-life and tissue distribution of NRCs were studied using radiolabeled NRCs. Within the circulation, the half-life of NRCs was 21 hr and extravascularly, they were distributed mainly in and metabolized by the reticuloendothelial system within 7 days. Our observations suggest that the NRCs prepared and investigated in this study are efficient oxygen carriers without causing serious adverse reactions and can be prepared free from pathogenic micro-organisms by special filtration technique before encapsulation of Hb. Currently, experiments are ongoing to control auto-oxidation of oxyHb to metHb which is higher in NRCs than in native red cells at physiological conditions.

Animals↗

A case of radiation-induced rectal cancer developing after a long-term follow-up.

A case of radiation-induced rectal cancer is presented. In November, 1971, a 58-year-old woman had a stage II squamous cell carcinoma in the uterine cervix. She underwent a hysterectomy and postoperative radiotherapy. External pelvic irradiation of 10 MV x-ray was carried out in 15 fractions of 2 Gy daily, with a total dose of 30 Gy, and intracavitary radium insertion with a total dose of 960 mg hours (20 mg x 48 hours). She had been followed-up in our department since 1972, when rectal bleeding occurred. Proctoscopy and periodical biopsies were performed when the patient visited our hospital. There was no evidence of malignant tumor cells nor of recurrent cervical cancer from 1973 to 1989. In August, 1990, a biopsy specimen taken from a rectal ulcer revealed a malignant mucinous adenocarcinoma. The time interval between the radiotherapy and the development of the rectal cancer was 19 years. Microscopically, the main lesion was situated in the granulation tissue covered with the regenerating mucosal epithelium, and histologically was found to be a mucinous adenocarcinoma. Other radiation damage was additionally found including colitis, endarteritis and intestinal wall fibrosis. The evidence strongly suggested the present case to be one of radiation-induced rectal cancer.

Adenocarcinoma, Mucinous↗

[Treatment of advanced colorectal cancer with long-term continuous infusion of 5-fluorouracil].

The purpose of the study was to evaluate the efficacy of long-term continuous administration of 5-fluorouracil (5-FU) in ambulatory patients with colorectal cancer. Nineteen patients with advanced colorectal cancer were treated with continuous intravenous infusion of 5-FU (500 mg/day). The minimum duration of therapy was projected to be four weeks. In some patients 4 weeks interval therapy was selected and in other patients the duration of therapy was open-ended. A portable pump was used to deliver 5-FU continuously into the venous system at home. The pump had a subcutaneously placed port connected to a central venous catheter. In 19 patients, the duration of 5-FU infusion was 56 to 427 days (median: 139 days), and cumulative doses of 5-FU ranged from 28 to 173.5 g (median 69.5 g). Five patients achieved partial response (response rate: 26.3%), and the response lasted 80 to 339 days (median: 204 days). The fifty-percent survival time was 17 months. In 16 patients whose serum CEA level was elevated, there was a decrease to less than 50% among 11 patients (69%). Dose limiting toxicity was stomatitis in 4 patients and hand-foot syndrome in one, but they recovered after interruption of the infusion. Hematological toxicity was generally mild. No infusion-system related complication was encountered. Patients were able to be discharged and live at home during 82% of their survival period, while receiving this therapy. We concluded that this treatment is effective with tolerable toxicity and can be conducted at home.

Aged↗

A role of heat shock proteins for homologous recombination in Escherichia coli.

Effects of mutations in heat shock protein genes on homologous recombination in Escherichia coli were examined by measuring intra-molecular recombinations in the plasmid, pIK43. Recombination frequencies in the groES, groEL and dnaK mutants were decreased 6 to 21% of those of the isogenic wild type strain, at a sub-lethal temperature. Thus, the heat shock proteins GroES, GroEL and DnaK apparently participate in homologous recombination in Escherichia coli.

Bacterial Proteins↗

Distinctive expression of lprcg in the heterozygous state on different genetic backgrounds.

Much knowledge of the etiopathogenesis of human autoimmune diseases has been obtained from the mutant mouse models carrying lpr and gld. These autoimmune genes have been regarded as autosomal recessive. The novel lymphoproliferative and autoimmune mutation lprcg is unique in its interaction with gld despite their different chromosomal locations: chromosomes 19 and 1, respectively. Both lprcg and lpr mutations are shown to be the defects in the Fas antigen gene that controls apoptosis. Evidence has been provided for the partial expression of lpr in the heterozygous state and the significant influences of background genes on lpr-induced autoimmune disorders. To investigate the expression of the heterozygous lprcg and the effects of background genes on it, anatomical, serological, and pathological manifestations were compared among lprcg/lprcg,lprcg/+, and +/+ mice on both MRL/MpJ (MRL) and CBA/KlJms (CBA) backgrounds. On the MRL background, lymph nodes (LN) and spleens of lprcg/+ were significantly larger in weight than those of +/+, but far lower than those of lprcg/lprcg mice. In accord with this, these lprcg/+ mice had intermediate levels of anti-single-stranded DNA antibodies, circulating immune complexes, and serum Igs between those of lprcg/lprcg and +/+ mice and were similar to lprcg/lprcg mice in severity of glomerulonephritis. However, accumulation of anomalous CD4-8- T cells characteristic of the lpr disease was not proved in the enlarged lprcg/+ LN. On the CBA background, the LN and spleen weight increases in lprcg/+ were statistically significant compared to +/+ mice but were minimal, being regarded as clinically insignificant. In support of this, lprcg/+ mice were not different from +/+ mice in any of the serological and pathological parameters examined. The results clearly demonstrate that the lprcg gene can function to induce autoimmune disorders in the heterozygous state on the MRL but not on the CBA background.

Animals↗

Proliferative activity of gastric cancer assessed by immunostaining for proliferating cell nuclear antigen.

The growth activity of 107 gastric carcinomas was assessed by immunohistochemical staining for formalin-fixed, paraffin-embedded tissue with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). When the tumor doubling times (Tds) of 10 patients were estimated from the serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9, there was an inverse correlation between the Tds and PCNA labeling index (LI) at P = 0.055. Flow-cytometric analysis was carried out by double staining for PCNA and DNA using fresh materials from 14 patients. The PCNA-positive cell fraction revealed by flow cytometry showed a good linear correlation with PCNA LI in routinely stained tissue. The LI of well-differentiated adenocarcinoma was significantly higher than that of the poorly differentiated type. When the LI was analyzed in well- or poorly differentiated adenocarcinoma, the value was significantly higher in the well-differentiated type with hepatic metastasis and in the poorly differentiated type with lymph node metastasis.

Adenocarcinoma↗

Differential expression of gelatinase B (MMP-9) and stromelysin-1 (MMP-3) by rheumatoid synovial cells in vitro and in vivo.

Primary cultures of adherent rheumatoid synovial cells (ASC) are comprised of variable proportions of fibroblasts, macrophages and stellate cells (activated fibroblasts). These cultures were shown to produce the metalloproteinases stromelysin-1 (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9) by Western blotting and zymography techniques. Immunolocalisation studies showed that MMP-3 was mainly produced by the fibroblastic cells whereas MMP-9 was restricted to macrophages (CD68 positive). Subcultured synovial fibroblasts, devoid of macrophages, did not produce MMP-9 as judged by zymography and immunolocalisation; but when stimulated with phorbol myristate acetate and interleukin-1 alpha both MMP-9 and MMP-3 were co-expressed. These 'activated' fibroblasts assumed a dendritic or stellate morphology, which in localisation studies was usually associated with enhanced enzyme production. Immunolocalisation studies of rheumatoid synovial tissue showed that relatively few cells were positive for MMP-3 and MMP-9. Localisation of MMP-9 corresponded to a proportion of macrophages positive for the CD68 marker throughout the synovial tissue. MMP-3 localisation was not associated with the macrophage marker, but was observed in both the synovial lining layer and deeper stromal locations. Widespread distribution of both enzymes was not observed in fresh tissues, but this increased in tissues subjected to short-term explant cultures. Thus, both in vitro and in vivo studies indicated that synovial fibroblasts or B-cells are effective producers of MMP-3 whereas macrophages elaborate MMP-9, observations that demonstrated different metalloproteinase phenotypes under similar environmental conditions.

Arthritis, Rheumatoid↗

A pharmacodynamic and pharmacokinetic study of fluoropyrimidines in a nude mouse system and in postoperative patients with gastric cancer.

To evaluate the effect of the oral fluoropyrimidines, tegafur and uracil (UFT) and 5-fluorouracil (5-FU), a pharmacodynamic analysis was conducted using a nude mouse system and patients. In the nude mouse system, UFT and 5-FU showed similar marginal effects against the human tumor xenograft Co-4, and the concentration of 5-FU in serum 1 h after the last administration being 0.04 micrograms/ml, which was assumed to be the minimum effective concentration. (MEC). Postoperative patients were subdivided into three groups, being: those who underwent subtotal gastrectomy and received UFT; those who underwent subtotal gastrectomy and received 5-FU; and those who underwent total gastrectomy and received UFT. In the UFT groups, the concentration of 5-FU in the portal and peripheral blood showed similar elimination in terms of the peak concentration (Cmax) and the area under the curve (AUC). In the 5-FU groups, the AUC and Cmax were significantly higher in portal blood than peripheral blood. The concentrations in the portal blood of the 5-FU group and in the portal and peripheral blood of the UFT group were significantly higher than the MEC (0.04 micrograms/ml). From these pharmacodynamic data, it was concluded that postoperative chemotherapy with oral fluoropyrimidines can achieve the MEC in portal and peripheral blood.

Adenocarcinoma↗

Biofeedback therapy in the treatment of tinnitus.

Seven patients were treated with electromyographic biofeedback therapy for intractable tinnitus which was supposed to be reinforced by mental distress and muscle tension. Three patients, who succeeded in decreasing electromyographic levels of the frontal muscle, were able to reduce tinnitus and relieve anxiety. One patient could eliminate tinnitus only during biofeedback sessions, but the efficacy was not continuous in daily life. The other three patients, who failed to decrease electromyographic levels, did not obtain favorable results. It is suggested that biofeedback therapy appears to be of greatest benefit when muscle tension and mental distress are the cause of magnification of the tinnitus symptoms.

Acute Disease↗

Fatal angioedema associated with enalapril.

A 37-year-old female with a history of hypertension for 5 years was brought to the emergency room with swelling of the tongue and neck after the second dose of enalapril. After administration of hydrocortisone by her physician, she went to the emergency room. Her dyspnea and dysarthria were relieved. However, she experienced recurrence of the symptoms followed by respiratory arrest. She suffered severe anoxic brain damage and died three days later. Although angioedema is a rare occurrence with the use of enalapril, it is potentially life threatening.

Adult↗

Clinicopathological characteristics of colorectal submucosal carcinoma with lymph node metastasis.

The clinicopathological characteristics of colorectal submucosal carcinoma with lymph node metastasis are described. Lymph node positive metastasis was found in 10 (11%) of 87 cases. The depth of submucosal invasion was classified as sm1, sm2 or sm3. Lymph node positive metastases were found in 18% of the cases at sm2 or more, in 31% of those without adenomatous components, in 39% of those with positive lymphatic permeation, in 41% of those with positive budding, and in 56% of all the moderately differentiated adenocarcinomas. These characteristics are risk factors and are important for the prediction of lymph node metastasis from colorectal submucosal carcinoma. Bowel resection with lymphadenectomy is indicated in the presence of any one or more risk factors.

Adult↗

Therapeutic rectoscopy for rectal tumors.

A surgical resection in the middle or upper region of the rectum is often technically difficult because of the anatomical inaccessibility of the site. A new rectoscopic operative technique reported by Buess et al. (1985, 1987, 1988) and Kipfmüller et al. (1988) permits microsurgery in the rectum and is less aggressive than other procedures. This technique was used in 7 patients with rectal tumors using an articulated monocular-optical system. The postoperative course in all patients was free from any complications and the patients were discharged at the latest on the eighth day after the operation. A stereoscopic optical system, a new surgical rectoscope, other special surgical instruments, as well as a modification to an insufflation device are necessary for improving the endoscopic operation.

Aged↗

Clinicopathological studies of multiple cancers in the large bowel and other organs.

During the past 17 years, 1,463 cases of cancer of large intestine, there were 117 cases (8.0%) with overlapping cancer in other organs. The male/female ratio was 1.0:1.1 and the mean age was 65.8 years old. The region of existence in other organs was in the order of frequency: stomach 28.3%, uterus 26.3%, and liver 8.1%. The location and histology showed almost similar results to that of single cancer. In comparison with single cancer, overlapping cancer cases showed a high complication rate of adenoma. So it was suggested that a region of cancer development was present but latent. The preceding cases of cancer of the uterus almost all underwent radiotherapy. About 36% of their histology of colon cancer were mucinous carcinoma suggesting at least the development of cancer by radiation.

Age Factors↗