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Biomedical subjects

H Takeyama

Publications and source records attributed to H Takeyama.

At least 91 records · Page 5Linked to original sources

Production of a novel monoclonal antibody, JT-95, which can detect antigen of thyroid carcinoma.

Monoclonal antibody (MAb) JT-95 was produced by immunization of mice with membrane fractions of a human thyroid carcinoma. Immuno-histochemical staining has demonstrated that the antigen recognized by JT-95 is strongly expressed in 95 (95%) of 100 cases of papillary carcinomas and in 3 (75%) of 4 cases of follicular carcinomas. In benign diseases of the thyroid gland, MAb JT-95 reacted with 0 (0%) of 39 adenomas, 1 (4%) of 21 adenomatous goiters, 0 (0%) of 8 hyperthyroidism specimens, and 3 (38%) of 8 chronic thyroiditis specimens. The antigen detected by MAb JT-95 has an apparent Mr 250,000 in thyroid carcinomas. Moreover, circulating antigen in thyroid carcinoma patients was detected by MAb JT-95 in an ELISA and in Western blotting. The circulating antigen has a Mr 105,000. MAb JT-95 conjugated with (131) I was administrated to nude mice bearing a human thyroid carcinoma. JT-95 131I accumulation at the transplanted tumor was visualized by autoradiography with 2.68-14.75-fold higher levels detected at the xenograft compared to that for normal organs. Based on these data, MAb JT-95 may be useful in the diagnosis detection and therapy of thyroid carcinoma.

Adenocarcinoma, Follicular↗

[Intraperitoneal administration of carboplatin loaded alpha-tricalcium phosphate (alpha-TCP) particles in rats bearing abdominal carcinomatosis].

It is difficult to treat abdominal carcinomatosis with conventional chemotherapy, and many kinds of localized chemotherapy have been attempted. We used alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier in this study. alpha-TCP, which has chemically similar properties to human bone, has an excellent biocompatibility with human tissues and is biodegradable. The particles measured 50 to 100 microns in diameter, were round in shape and very porous. These particles have many open micro-pores of about 1 to 3 microns, which are beneficial for containing drugs. The compatibility and biodegradation of alpha-TCP particles were studied following intraperitoneal (ip) administration in normal rats. The following results were obtained: (1) alpha-TCP particles were intaken in the great omentum, and dissolved gradually. (2) The efficacy of ip administration of carboplatin-loaded alpha-TCP (alpha-TCP-CBDCA) was examined using a Donryu rat model with AH130 abdominal carcinomatosis. The alpha-TCP-CBDCA contained 200 mg alpha-TCP and 4 mg CBDCA. The pharmacokinetics of CBDCA following ip administration of alpha-TCP-CBDCA were studied. Pt levels in ascites and great omentum were higher in the alpha-TCP-CBDCA ip from 0.5 to 168 hours than those in the free-CBDCA ip and iv groups. These results suggest that the efficacy of CBDCA may be enhanced by utilizing alpha-TCP particles as a drug delivery carrier.

Animals↗

[Polycythemia].

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Diagnosis, Differential↗

Phylogenetic analysis of a novel sulfate-reducing magnetic bacterium, RS-1, demonstrates its membership of the delta-Proteobacteria.

Most of the 16S ribosomal RNA gene of a sulfate-reducing magnetic bacterium, RS-1, was sequenced, and phylogenetic analysis was carried out. The results suggest that RS-1 is a member of the delta-Proteobacteria, and it appears to represent a new genus. RS-1 is the first bacterium reported outside the alpha-Proteobacteria that contains magnetite inclusions. RS-1 therefore disrupts the correlation between the alpha-Proteobacteria and possession of magnetite inclusions, and that between the delta-Proteobacteria and possession of greigite inclusions. The existence of RS-1 also suggests that intracellular magnetite biomineralization is of multiple evolutionary origins.

Bacteria↗

Perforated acute appendicitis in a patient with AIDS/HIV infection: report of a case.

We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).

AIDS-Related Opportunistic Infections↗

Report on the first annual survey of home parenteral nutrition in Japan.

An annual survey of the current national status of home parenteral nutrition (HPN) in Japan was begun in 1991, with a total of 231 registered patients from 142 institutions providing adequate data for evaluation and analysis. HPN was given for an average of 683 +/- 764 days to 93 patients with malignant diseases and 138 with benign disease, including 53 with inflammatory bowel disease and 79 with short bowel syndrome, 107 (46.3%) of whom were successfully rehabilitated. By the end of 1990, 61% of the patients investigated were still on HPN, 7% had already completed HPN, and 26% had died, the deceased accounting for 54% of the patients with malignant diseases and 7% of those with benign diseases. A total of 321 catheters had been used by all 231 patients, the most common being the subcutaneously implanted type, accounting for 33% of all catheters. By the end of 1990, 32% of these 321 catheters were still in place, 18% had been removed on the termination of HPN and 44% had been removed due to complications of total parenteral nutrition, including 20% for catheter fever. Rehospitalization was required in 62% of the patients, the cause being HPN-related in 21% of the total patients. Metabolic complications were experienced by 60% of the patients, but none of these were severe although 6% required hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Binding of pig sperm receptor in the zona pellucida to the boar sperm acrosome.

Pig zona pellucida (ZP) contains three families of glycoproteins: PZP2, PZP3 alpha and PZP3 beta. PZP3 alpha mediates the binding of the ZP to spermatozoa. In this study, the binding site of pig ZP on boar spermatozoa and the zona-binding proteins of boar spermatozoa were studied using chemically modified zona glycoproteins or anti-pig ZP antiserum. Endo-beta-galactosidase-digested PZP3 alpha (E beta G-PZP3 alpha), which is deficient in sulfated N-acetylpolyactosamine, as well as solubilized ZP, bound to the acrosomal region of acrosome-damaged or partially acrosome-reacted spermatozoa. However, they did not bind to acrosome-intact or fully acrosome-reacted spermatozoa. Solubilized ZP did bind to the acrosomal cap released upon acrosome reaction. In western blot analyses, E beta G-PZP3 alpha bound to the sperm proteins with molecular masses similar to proacrosin-acrosin and the binding was inhibited by fucoidan and anti-pig acrosin antiserum. These results suggest that the binding site of solubilized pig ZP and E beta G-PZP3 alpha on spermatozoa is located mainly in the acrosomal matrix and on the membranous compartments in the acrosome and suggest that E beta G-PZP3 alpha binds to proacrosin-acrosin. The binding of E beta G-PZP3 alpha to proacrosin-acrosin may be involved in the binding of the ZP to the acrosome of partially acrosome-reacted spermatozoa.

Acrosome↗

[Antitumor effects of liposome-entrapped carboplatin (Lipo-CBDCA) after intraperitoneal administration in rats bearing carcinomatous peritonitis].

We examined the distribution of Lipo-CBDCA after intraperitoneal administration and antitumor effects in rats. The serum levels of platinum in Lipo-CBDCA were lower than in free-CBDCA intraperitoneal or intravenous administration at 15 and 30 min. after administration. After 3 hours, Lipo-CBDCA showed higher levels of serum platinum than free-CBDCA. These data showed the slow release of Lipo-CBDCA. The antitumor effects of Lipo-CBDCA were studied in rats with peritoneal dissemination due to AH 130 tumors. Intraperitoneal treatment with Lipo-CBDCA prolonged the life span significantly compared with Lipo-CBDCA. No side effects of chemotherapy were found in the liver, kidney, spleen or small intestine. A gastric cancer patient suffering from carcinomatous peritonitis with remarkable ascites was treated with Lipo-CBDCA intraperitoneally. After several injections of Lipo-CBDCA, the ascites disappeared completely and the CEA level of ascites decreased dramatically. These results indicate that intraperitoneal chemotherapy with Lipo-CBDCA may be more effective than free-CBDCA to manage carcinomatous peritonitis, and may be therapeutically useful without toxic side effects.

Animals↗

[Marked bone marrow necrosis preceding acute monoblastic leukemia].

Bone marrow necrosis is rarely diagnosed during life but is more often seen at autopsy by accident. The prognosis of patients with bone marrow necrosis secondary to neoplastic disease is extremely poor. We described a 53-year-old man with bone marrow necrosis preceding acute monoblastic leukemia. He was admitted in June, 1994, for continuous back pain and marked elevation of serum lactate dehydrogenase. After admission, a hematologic examination showed progressive pancytopenia in peripheral blood and bone marrow necrosis. He was diagnosed as AML (M5) from the sudden appearance of leukemic blasts in the peripheral blood two months later. Induction therapy was immediately administered according to JALSG-92 protocol. The patient suffered from tumor lysis syndrome after chemotherapy, but complete remission was achieved by dialysis.

Bone Marrow↗

[Efficacy of early administration of G-CSF after intensive chemotherapy in acute leukemia: a randomized controlled trial. Tokai Infection Study Group on Hematological Disorders].

The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia and infection was studied in a randomized trial in patients receiving intensive chemotherapy for acute leukemia. Fifty seven patients with acute leukemia (35 cases of refractory acute myeloid leukemia, 19 cases of acute lymphoblastic leukemia and 3 cases of blast crisis of chronic myeloid leukemia) were given G-CSF under either of the following two conditions; 1) Group A: starting G-CSF (200 micrograms/m2iv) administration 24 hrs after chemotherapy. 2) Group B: the same dose of G-CSF administration after a febrile episode of 38 degrees C with neutropenia (less than 1,000/microliters). Five patients were excluded from the study. Group A (27 patients) showed a shorter febrile period (2.15 +/- 2.98 days) than the 25 patients of Group B (3.40 +/- 4.78 days), but the difference was not statistically significant. Compared to Group B, Group A showed significantly early recovery of neutrophil counts as well as early recovery from documented infections. There was no evidence that early administration of G-CSF accelerates the growth of leukemic cells nor causes early relapse of acute leukemia.

Acute Disease↗

Sequence of a 2.6-kb cryptic plasmid from a marine cyanobacterium Synechococcus sp.

We have shown previously that the copy number of plasmid pSY10 from the marine cyanobacterium Synechococcus sp. NKBG 042902 is dependent on the salinity of the growth medium. We report here the complete nucleotide sequence (2561 bp) of this plasmid. The longest open reading frame, ORF-B (1.08 kb), occurs on a 1.6-kb EcoRI fragment. This ORF encodes a putative protein which is 360 aa residues in length and is 37.8% homologous to the replication protein of plasmid pCA2.4 from Synechocystis sp. strain PCC 6803, 35.8% homologous to an ORF from the Nostoc plasmid pGL2, and 33.2% homologous to the ORF of a plasmid from Lactobacillus plantarum, pC30il. Highly conserved regions of amino acid sequence were also found between ORF-B and other bacterial plasmids.

Amino Acid Sequence↗

Both VH and VL regions contribute to the antigenicity of anti-idiotypic antibody that mimics melanoma associated ganglioside GM3.

Previously we developed a murine monoclonal anti-idiotype (anti-id) antibody (4C10) that mimics the melanoma-associated ganglioside antigen GM3, that is, it carries the internal image of GM3. 4C10 was made against the human monoclonal antibody (HuMAb) L612, which reacts with several types of human cancer cells, including melanoma and breast cancer. To reduce mouse components of 4C10, the constant region was replaced by a human constant domain to form the murine/human chimeric anti-id antibody TVE-1. In the present study, we sought to determine which chain (VH or VL) of the anti-id is responsible for the antigenicity of GM3. The TVE-1 VH and VL expression vectors were simultaneously transfected with either the VH or VL expression vector of a murine-human chimeric IgG antidansyl haptenic antibody, resulting in the construction of three different combinations of VH and VL chimeric antibodies. These IgG molecules were produced from the transfectomas, and their reactivity to HuMAb L612 was tested. Neither of the IgG proteins that had cross-combined the VH-VL pair showed positive results, suggesting that both heavy and light chains are required to express the antigenicity. The in vivo antigenicity of this chimeric anti-id was confirmed by skin tests in melanoma patients receiving active specific immunotherapy.

Animals↗

Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric carcinoma.

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in another 18 patients. Prior to radical gastrectomy, Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 ml of Lipo-ADR was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of F-ADR. The ADR levels (micrograms/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4); and 11.9 +/- 4.80 on day 4 (n = 6). Those after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4); and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (P < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Such preoperative adjuvant chemotherapy targeting the regional lymph nodes may be useful for preventing the lymph node recurrence of gastric carcinoma.

Adult↗

Serum preparation and methods for the large-scale production of IgG monoclonal antibody.

In this study we demonstrated that fetal calf serum (FCS) depleted of IgG by protein G affinity chromatography (G-FCS) is superior to whole FCS or serum-free culture media as a culture supplement for the production of purified IgG monoclonal antibodies (MAb). One hundred ml FCS was applied to a 25 ml protein G Sepharose 4 Fast Flow Column, which was shaken gently for 2 days at 4 degrees C. The procedure was repeated using a protein G column for an additional day. G-FCS was used at a concentration of 5% in RPMI 1640 medium to grow the mouse myeloma cell line P3X63.Ag8.653, which secretes an IgG-1 mouse-human chimeric monoclonal antibody (TVE-1). Cell density, viability, doubling time, and antibody production were used as indices to compare the efficacy of this medium with that of whole FCS medium, AIM-V (Gibco, USA) and other serum-free media. The results demonstrate that cell growth and antibody production in -GFCS medium did not differ significantly from that in FCS medium, but were significantly better than in the serum-free media (p < 0.001). TVE-1 antibody in the spent tissue culture media was purified by 50% ammonium sulfate precipitation and Protein A affinity chromatography. An antibody that was more than 99% pure was obtained. Endotoxin analysis revealed that the IgG depletion process does not generate a significant level of endotoxin in FCS (< 0.06 EU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A clinical study of sixteen polycythemia vera cases--acute myeloblastic leukemia in patients with polycythemia vera].

The clinical course of 16 patients with polycythemia vera (PV), treated in the period 1982 to 1993, was shown. Splenomegaly occurred in three fourths of these patients (75%), and hypertension was a major symptom. Thrombosis such as myocardial infarction and cerebral infarction was noted. Eight patients was treated with myelosuppressive agents and the 8 other patients were treated with phlebotomy. A 70-year-old male who was treated with mitobronitol (DBM) developed acute myeloblastic leukemia (AML) 11 years later. He was treated with multi-combination chemotherapy (BHAC-DMP), and entered complete remission, followed by early relapse. He became refractory to chemotherapy and died of acute pneumonia 6 months later. Median survival of 16 cases of PV was more than 10 years, and long-term treatment and care are necessary.

Adult↗

[A case of essential thrombocythemia with clonal evolution in the terminal phase].

This 50-year-old male was admitted to the hospital on April 1983 with complaints of severe chest pain attacks 2 weeks previously. Laboratory data: On admission the blood findings were Hb 14.3 Gm/dl of blood, RBC 4.70 million/mm3, WBC 11,600/mm3 and a platelet count of 1.1 million/mm3. ECG showed elevation of ST-T in V1 to V4. Serum LDH and CPK levels were high. He was diagnosed as acute myocardial infarction with thrombocythemia. Three days after admission he abruptly fell into a semicomatose state and left hemiplesia. Head computed tomography showed a large, low-density lesion in the right mid-cerebral artery area, and we also diagnosed cerebral infarction. He was given nimustine (ACNU) 100 mg/week three times as remission induction therapy. For maintenance chemotherapy, at first we administered mitobronitol (DBM) 150 mg/day then changed to intermittent administration of ACNU 100 mg. On September 1991, the patient was admitted to the hospital with progressive anemia and uncontrollable thrombocythemia. Bone marrow chromosome analysis revealed aneuploidy. The patient received interferon alpha 3 million unit/day. The thrombocythemia could be controlled but his general condition deteriorated. On April 1992, he died of interstitial pneumonia.

Aneuploidy↗