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Biomedical subjects

T Fujimura

Publications and source records attributed to T Fujimura.

At least 181 records · Page 10Linked to original sources

[Refractory idiopathic thrombocytopenic purpura which responded to protein A column].

Currently, there is no satisfactory therapy available for patients with chronic idiopathic thrombocytopenic purpura (ITP) who are unresponsive to conventional therapeutic modalities. In this report, we describe a patient with chronic refractory ITP treated with immobilized protein A in an extracorporeal system. The patient was a 74 years old male diagnosed as ITP in 1980. Despite steroid therapy, the disease progressed and the patient exhibited ecchymosis and gum bleeding which was unresponsive to intravenous gammaglobulin therapy. Severe gastrointestinal bleeding was evident and administration of danazol was discontinued due to liver dysfunction. The patient was treated with extracorporeal protein A immunoabsorption. The patient's whole blood (200-300 ml per treatment) was separated into plasma and cellular components and the plasma was passed through an immunoabsorption column containing 200 mg of covalently bound protein A. The treated plasma and cellular components were returned to the patient. After 4 immunoabsorption treatments, the platelet counts elevated and there was evidence of improvement in gastrointestinal bleeding. This report indicates that protein A immunoabsorption therapy should be considered in patients with chronic refractory ITP.

Aged

[DNA ploidy pattern in diffuse infiltrating carcinomas of the stomach].

Analysis of DNA ploidy patterns was performed on 76 diffusely infiltrating carcinomas of the stomach and the results correlated with histologic findings and outcome. Twenty six cases were diploid (34%) and 50 cases were aneuploid. There was no correlation between DNA ploidy and histologic type, depth of invasion, lymphatic invasion, evidence of peritoneal dissemination or curability. In aneuploid tumors, incidence of vascular invasion was significantly higher than that in diploid tumors (p less than 0.05). In addition, the patients with aneuploid tumors had a poor prognosis than with diploid tumors. These results indicate that DNA ploidy patterns may possibly be a useful prognostic marker for diffusely infiltrating carcinomas of the stomach.

Aneuploidy

Gene overlap results in a viral protein having an RNA binding domain and a major coat protein domain.

L-A double-stranded RNA (dsRNA) replicates in vivo in yeast in a conservative, asynchronous (first [+] strand then [-] strand), intraviral process. New particles are formed by packaging (+) strands. Added viral (+) single-stranded RNA (ssRNA) is specifically bound by empty virus-like particles (VLPs) and, in a reaction requiring a host factor, is converted in vitro to dsRNA. We find that the isolated binding complex replicates only if it was formed in the presence of the host factor. The VLP minor 180 kd protein, but not the major coat protein, has ssRNA binding activity on Western blots. The 180 kd protein shares a common antigenic domain with the major coat protein, the latter known to be encoded by L-A dsRNA. The 180 kd protein, but not the major coat protein, also shares an antigenic domain with a sequence encoded by the 3' end of the L-A (+) strand. Thus the 180 kd protein is also encoded by L-A dsRNA and consists of a major coat protein domain and a ssRNA binding domain.

Amino Acid Sequence

Correlation of DNA ploidy and proliferative activity in human gastric cancer.

Analysis of DNA ploidy patterns was performed on 129 cases of primary gastric cancer and the results were correlated with histologic findings and in vivo bromodeoxyuridine (BrdU) labeling. Forty-nine cases were diploid (38%) and 80 cases were aneuploid (62%). There was no correlation between DNA ploidy and histologic type. In aneuploid tumors, incidence of lymphatic invasion, lymph node metastasis, and rate of advanced cases were significantly higher than those in diploid tumors. During the follow-up period of 5 to 10 years, 23 of 40 patients (55%) with aneuploid tumors died of disease within 3 to 120 months. Only 13 of 36 patients (36%) with diploid tumors died of disease. The BrdU labeling indices (BrdU LI) ranged from 2.8% to 26.7%, with a mean of 10.4%. There was no correlation between BrdU LI and histologic type or stage. The mean BrdU LI of early cancers was 8.1%. The mean BrdU LI of advanced cancers was 11.9%. The BrdU LI of cancers with lymphatic invasion or lymph node metastasis was higher than those without them. The mean BrdU LI of diploid cancers was 6.0%. The mean BrdU LI of aneuploid cancers was 11.9%. There was a good correlation between BrdU LI and DNA ploidy patterns. These results indicate that DNA ploidy patterns and BrdU LI may possibly be useful prognostic markers for gastric cancers.

Bromodeoxyuridine

Replicase of L-A virus-like particles of Saccharomyces cerevisiae. In vitro conversion of exogenous L-A and M1 single-stranded RNAs to double-stranded form.

Virus-like particles that contain L-A double-stranded RNA are known to have transcriptase activity whose product is L-A single-stranded plus RNA. In low salt conditions, these particles release their double-stranded RNA and can then use added plus L-A or plus M1 single-stranded RNAs as templates to synthesize their respective double-stranded RNAs. The reaction requires dialyzed L-A virus-like particles as the source of the enzyme, a partially purified cell extract (host factor(s)), added single-stranded RNA as a template, and polyethylene glycol 6000, along with four NTPs. Crude host factor extracts prepared from mak3 or mak10ta mutants also support the reaction as effectively as that from a wild type strain, while a crude extract prepared from a pet18 mutant grown under the nonpermissive conditions is less effective. Template specificity of the in vitro reaction is the same as that expected for the enzyme reaction in vivo. Plus L-A and plus M1 single-stranded RNAs, but not 18 S rRNA, are converted to their respective double-stranded RNAs with net RNA synthesis. The newly synthesized strand of M1 double-stranded RNA is a full-length minus strand. This demonstration of replicase activity in the mature L-A virus-like particles which contain L-A double-stranded RNA is consistent with our previous L-A double-stranded RNA replication model; the difference between the mature L-A virus-like particles and L-A double-stranded RNA-synthesizing particles (expected to be replication intermediates in vivo) is just that the former contain L-A double-stranded RNA, while the latter contain L-A plus single-stranded RNA.

DNA Replication

Symptomatic accessory lobe of the liver associated with hyperthyroidism.

A case of symptomatic accessory lobe of the liver occurred in a 15-year-old Japanese girl with hyperthyroidism. The patient presented with acute abdominal distress; at operation, a twisted necrotic mass of the accessory lobe of the liver was found. A review of the literature failed to show a previously reported instance in a child.

Adolescent

Site-specific binding of viral plus single-stranded RNA to replicase-containing open virus-like particles of yeast.

X double-stranded RNA is a deletion mutant of L-A double-stranded RNA and is encapsidated in viral particles by the L-A-encoded major coat protein. X double-stranded RNA has all the cis sites necessary to be transcribed, encapsidated, and replicated. We have cloned X double-stranded RNA and sequenced it. The complete X double-stranded RNA sequence deduced indicates that the first 25 bases of the X plus-strand 5' end originated from the 5' end of the L-A plus strand and that most, if not all, of the rest comes from the 3' end of the L-A plus strand. The X plus strand made by X double-stranded RNA-containing virus-like particles binds specifically to empty open virus-like particles and is converted by these particles to X double-stranded RNA. RNA transcripts of the X complementary DNA clones and deletion derivatives thereof were made in vitro by T7 and T3 RNA polymerases and tested for specific binding to the virus-like particles. The results suggest that the binding is due to the sequence UUUGGCCAGG, 370 bases upstream from the X plus-strand 3' end. This sequence is also present in the M1 plus strand 140 bases from its 3' end.

Amino Acid Sequence

[Combined hepatic arterial infusion chemotherapy with transcatheter arterial embolization and hyperthermia in primary liver cancer].

Intrahepatic arterial infusion chemotherapy (HAI) was performed for 20 hepatocellular cancer (HCC) patients and 7 cholangiocellular cancer (CC) patients. HAI combined transcatheter arterial embolization (TAE) and/or hyperthermia were performed for 10 HCC and 3 CC patients. The effective responses were shown in 6 HCC and 1 CC patients who were treated with HAI-TAE-hyperthermia combination therapy, and 2 CC patients who were treated with HAI-hyperthermia combination therapy. The 1 and 2-year cumulative survival rate was 100% and 33.3%, respectively, for HCC patients treated with HAI-TAE-hyperthermia therapy. The 1 and 2-year survival rate for HCC patients treated with HAI therapy was 19.5%, and 7.3%, respectively. Generalized Wilcoxon test revealed that the survival was favorable for patients treated with HAI-TAE-hyperthermia therapy as compared with patients given with HAI therapy. Almost the same results were obtained in CC patients. These results suggest that the HAI-TAE-hyperthermia combination therapy was favorable for the treatment of advanced liver cancer.

Adenoma, Bile Duct

[Malignancy in gastric carcinoma, with special reference to the DNA ploidy and proliferative activity].

Analysis of DNA ploidy patterns was performed on 129 primary gastric cancers and the results correlated with histologic findings and in vivo bromodeoxyuridine (BrdU) labeling. Forty-nine cases were diploid (38%) and 80 cases were aneuploid. There was no correlation between DNA ploidy and histologic type. In aneuploid cancers, incidence of lymphatic invasion, lymph node metastasis and rate of advanced cases were significantly higher than those in diploid tumors. During the follow-up period of 5-10 years, 23 of the 40 patients (55%) with aneuploid tumors died of disease within 3-120 months. Only 13 of the 36 patients (36%) with diploid tumors died of disease. The BrdU labeling indices (BrdU LI) were from 2.8% to 26.7%, with a mean of 10.4%. There was no correlation between BrdU LI and histologic type or stage. The mean BrdU LI of early cancers was 8.1%, of advanced cancers, 11.9%. BrdU LI of cancers with lymphatic invasion or lymph node metastasis was higher than those without them. The mean BrdU LI of diploid cancer was 6.0%, of aneuploid cancers, 11.9%. There was a good correlation between BrdU labeling indices and DNA ploidy patterns. These results indicate that determination of DNA ploidy patterns and growth fractions by BrdU labeling may be useful in the conjecture of prognosis of the patient and in the selection of patients from various modalities.

Aneuploidy

[A case of disappearance of peritoneal dissemination in gastric cancer induced by continuous hyperthermic peritoneal perfusion with cisplatin and mitomycin C].

A 58-year-old woman who had undergone subtotal gastrectomy for advanced gastric cancer yielded massive ascites after 6 months. The cytology of ascites showing Class V indicated recurrence of peritoneal dissemination in the gastric cancer. Since laparotomy disclosed diffusely small tubercular seedings in all areas of the peritoneal cavity, she received continuous hyperthermic peritoneal perfusion (CHPP) with 300 mg Cisplatin and 30 mg Mitomycin C. After CHPP ascites disappeared for 4 months. Macroscopically and microscopically, there was no cancerous lesion in the peritoneal cavity by following second-look operation. This result encouraged us to try therapeutic CHPP for overt peritoneal dissemination.

Ascitic Fluid

Neutrophil-mediated tumor cell destruction in cancer ascites. II. A OK-432 attracts killer neutrophils through activation of complement C5.

When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, the number of neutrophils with cytotoxic activity against tumor cells was increased in the peritoneal cavity immediately after the OK-432 injection. In order to investigate the underlying mechanisms of such neutrophil accumulation, a possible neutrophil chemotactic activity in ascitic fluid was assayed by a modified Boyden method. The chemotactic activity for neutrophils was found significantly higher 6 hr after the OK-432 injection. OK-432 along had no direct chemotactic activity for neutrophils. The chemotactic activity was generated in vitro when ascitic fluid from patients without OK-432 treatment was incubated with OK-432 for 30 min at 37 degrees C. However, preheating of the fluid at 56 degrees C for 30 min or the addition of EDTA to the fluid resulted in the failure of generation of the chemotactic activity after the incubation with OK-432. The addition of EGTA did not show a significant effect. The chemotactic activity in ascitic fluid was found near cytochrome c marker (MW 12,400 D), when fractionated by Sephadex G-200 gel chromatography. The chemotactic activity was heat stable, nondialyzable, and neutralized completely with anti-human complement C5 antibodies. These results suggest that C5a generated via the alternative pathway activated by OK-432 may be responsible for the infiltration of killer neutrophils in the peritoneal cavity in patients with malignant ascites when they are treated by the intraperitoneal injection of OK-432.

Adult

L-A double-stranded RNA viruslike particle replication cycle in Saccharomyces cerevisiae: particle maturation in vitro and effects of mak10 and pet18 mutations.

Previously, we found that log-phase cells of Saccharomyces cerevisiae contain a new type of viruslike particles containing only plus- strand L-A single-stranded RNA (ssRNA). These particles synthesize minus-strand RNA in an in vitro RNA polymerase reaction to produce L-A double-stranded RNA (dsRNA). The major class of particles contains L-A dsRNA and synthesizes plus-strand L-A ssRNA by a conservative mechanism. In this paper, we show that mutations in mak10 or the pet18 locus, which result in temperature-dependent replication of L-A dsRNA in vivo, also result in instability of the L-A dsRNA-containing (major class) viruslike particles in vitro. The L-A dsRNA (minus-strand)-synthesizing particles isolated by CsCl density gradient centrifugation synthesize plus-strand L-A ssRNA after completion of dsRNA (minus-strand) synthesis and have the same major coat protein as that of the major-class particles. Furthermore, the density of the dsRNA-synthesizing particles from wild-type cells shifts to that of the major-class dsRNA-containing particles as a result of the in vitro RNA polymerase reaction. Thus, L-A dsRNA-synthesizing particles undergo functional and structural maturation in vitro.

Genotype

[A case of parotid tumor showing remarkable regression following hyperthermo-chemo-radiotherapy].

A 72-year-old woman developed adenocarcinoma of the left parotid gland. Because of the excessive size of her tumor and the fact that she suffered from severe liver dysfunction, she was treated by hyperthermo-chemo-radiotherapy (HCR therapy). After ten sessions of radiofrequency hyperthermia with HEH 500 (13.56 MHz radiofrequency wave), 50-Gy irradiation from a linac and administration of 33.0g of tegafur in suppository form, the tumor mass showed remarkable regression decreasing in size by as much as 84% on computed tomography. Histologically the tumor which was resected under local anesthesia, showed almost total necrosis. The multidisciplinary HCR therapy was well tolerated and effective as a therapy for cancer in this case.

Adenocarcinoma

[Multimodal therapy using hyperthermia for gastric cancer--with special reference to histological studies].

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols

Malignant tumor and eosinophils. I. Prognostic significance in gastric cancer.

A prospective study with 647 gastric cancer was performed. Resected tumor specimens from 647 patients were examined with respect to eosinophil infiltration. Infiltration of the primary tumor by eosinophils was found to have a marked prognostic significance. Five years after the resection of tumor in the patients with gastric cancer, 29 of 51 patients (56.0%) who showed previously the infiltration of more than 100 eosinophils in tumor tissue were alive, while only 38.6% (61/158) of the patients with the infiltration of less than 100 eosinophils survived (P less than 0.05). Eosinophil infiltration in the resected tumor was detected in 157 patients (24%). The intensive degree of infiltration correlates well with a special pathologic type of cancer, poorly differentiated adenocarcinoma, the size of tumor mass and preoperative blood eosinophilia. The extract from tumors with the marked eosinophilic infiltration was highly chemotactic for eosinophils in vitro. The eosinophil chemotactic activity was found to be heat-labile and nondialyzable. It was therefore considered most likely that eosinophil infiltration in the tumor and blood eosinophilia observed in some patients with gastric cancer were caused by an eosinophil chemotactic factor of gastric cancer and the good indication of the prolonged survival of the patients.

Adenocarcinoma