Radioimmunotherapy: promising treatment of aggressive adult T-cell leukemia?
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Publications and source records attributed to H Taguchi.
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SUMMARY: An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.
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An HTLV-I-seronegative case of adult T-cell leukemia (ATL) carrying the HTLV-I genome is reported. Screening serological tests were negative and Western blot analysis revealed only a faint band for HTLV-I p24. Polymerase chain reaction (PCR) disclosed the presence of HTLV-I gag, pol, env, pX, and LTR sequences in the lymph node and peripheral blood. Southern blot analysis revealed a monoclonal integration of HTLV-I in the lymph node and peripheral blood. The tumor cells expressed viral antigens after short-term culture. The clinical course was consistent with ATL in that the patient exhibited hypercalcemia and abnormal lymphocytosis as well as hepatosplenomegaly and lymphadenopathy. We recommend that PCR analysis for HTLV-I be performed even in seronegative cases when ATL is clinically suspected.
We have characterized a human genomic clone carrying two pseudogenes for the proliferating cell nuclear antigen (PCNA), which were tandemly arranged on human Chromosome (Chr) 4. One is a processed pseudogene that showed a 73% nucleotide homology to the human PCNA cDNA and possessed none of the introns existing in the functional PCNA gene. This pseudogene presumably arose by reverse transcription of a PCNA mRNA followed by integration of the cDNA into the genome. The other is a 5' and 3' truncated pseudogene that showed a nucleotide homology to a 3' region of the exon 4 and to a 5' region of the exon 5 of the PCNA gene and did not have the intronic sequence between the exons 4 and 5. Both pseudogenes had the same nucleotide deletion as compared with the human functional PCNA gene. A phylogenetic analysis of PCNA gene family, including the functional PCNA gene and another PCNA pseudogene located on a different chromosome, revealed that the truncated pseudogene exhibits the closest evolutionary relationship with the processed pseudogene, suggesting that the truncated pseudogene was generated by duplication of the processed pseudogene after translocation to Chr 4. Furthermore, fluorescence in situ hybridization revealed that these pseudogenes are located on the long arm of Chr 4, 4q24.
PURPOSE: To compare the postoperative decentration of three-piece silicone intraocular lenses (IOLs) with polymide haptics and with polypropylene (PP) haptics and to determine whether the difference was caused by the haptic material. SETTING: Kimura Eye and Internal Medicine Hospital and Hitani Eye Clinic, Hiroshima, Japan. METHODS: Using a previously described photographic method, we calculated the postoperative decentration in randomly selected patients who had phacoemulsification and capsular bag implantation of three-piece silicone IOLs. In 64 patients, the IOL had polyimide haptics and in 57, PP haptics. One surgeon performed all the surgery using the same technique. RESULTS: Mean decentration of IOLs with polyimide haptics was 0.34 mm +/- 0.17 (SD) and of those with PP haptics, 0.48 +/- 0.30 mm. Although follow-up of the polyimide group was longer than that of the PP group (12.8 +/- 5.7 months and 8.7 +/- 4.0 months, respectively), decentration in the polyimide group was significantly smaller (P < .01). CONCLUSION: The lower rate of postoperative decentration in the IOLs with polyimide haptics was related to the haptic material.
The immunocytochemical localization of the 60-kDa heat shock protein (HSP) in Vibrio cholerae strain 569B was studied by transmission electron microscopy using a combination with the antigen-specific monoclonal antibody (5C3) and immunogold labelling. The labelling with gold particles in V. cholerae detected 2 types; the gold particles were exclusively detected in the cytoplasm for one type and in the periplasmic space for another type, suggesting that the 60-kDa HSP of V. cholerae corresponding immunologically to Escherichia coli GroEL may translocate from the cytoplasm to the periplasmic space in the V. cholerae cell.
We report, to our knowledge, the first case of mucoid impaction of the bronchi due to a hypersensitivity reaction to the monokaryotic mycelium of Schizophyllum commune. The patient was hospitalized because of mild asthma attacks, persistent cough, peripheral eosinophilia, and "gloved finger" shadows on a chest roentgenogram. Bronchoscopic examination disclosed mucoid impactions that consisted of accumulations of eosinophils, Charcot-Leyden crystals, and nondichotomously branched hyphae in B3, B9, and B10 of the left lung. Cultures of the mucous plugs and sputum samples yielded white, felt-like mycelial colonies that were later identified as the monokaryotic mycelium of S. commune by use of mating tests with established monokaryotic and dikaryotic strains of S. commune. The results of tests for serum antibody to S. commune cytosol antigen were positive. Repeated bronchoscopies for performing bronchial toilet were effective in removing the mucous plugs and relieving the patient's symptoms. We suggest that the monokaryotic mycelium of S. commune should be considered as one of the fungi that can cause hypersensitivity-related lung diseases.
Carboxypeptidase (CPase) Taq possesses the His-Glu-X-X-His sequence, which is the consensus sequence in the active site of zinc-dependent endopeptidases and amino-peptidases, at positions 276-280. Amino acid replacement of the conserved His and Glu drastically diminished the activity of CPase Taq, and the zinc content of the enzyme was also greatly reduced when either of the two His residues was replaced with Arg or Tyr. The results indicate that this sequence actually functions as the active site in CPase Taq, showing that CPase Taq is a novel type of zinc-dependent CPase that possesses the His-Glu-X-X-His active-site motif.
The expression of a 60-kDa heat shock protein (HSP60) on the cell surface of Helicobacter pylori was analysed by flow cytometry with polyclonal antibody directed to HSP60. All 13 strains of H. pylori examined expressed HSP60 on the cell surface, although the intensity of expression was different among the strains and depended on culture conditions. There was a correlation between the intensity of HSP60 expressed on the cell surface and the rate of adherence to human gastric carcinoma cells (MKN45) by H. pylori, but not with urease activity and production of vacuolating toxin. By flow cytometric analysis with monoclonal antibody (MAb) 3C8 against HSP60, the reactive epitope in the HSP60 of H. pylori was detected on the surface of MKN45 cells. Furthermore, it was shown that gastric epithelial cells were positively stained with MAb 3C8 in one of two biopsy specimens examined. These results suggest that there is a common epitope showing homology between H. pylori HSP60 and human gastric epithelial cells.
To determine amino acid sequences of the epitopes recognized by monoclonal antibodies (mAbs) 3C8 and 5C3 directed against Yersinia enterocolitica heat-shock protein (HSP60), a dot blot analysis was performed using synthesized peptides of Y. enterocolitica HSP60 such as peptides p316-342, p327-359, p340-366, p316-326, p316-321, p319-323, and p321-326 which represent positions of amino acids in Y. enterocolitica HSP60. The dot blot analysis revealed that 5C3 mAb reacted with p316-342, p316-326 and p321-326, and 3C8 mAb p316-342 and p316-326. These results indicate that the epitopes recognized by the mAbs were associated with eleven amino acids, Asp Leu Gly Gln Ala Lys Arg Val Val Ile Asn, of p316-326. The sequence homology between p316-326 of Y. enterocolitica HSP60 and the rest of the HSP60 family suggests that the five amino acids of Lys, Arg, Val, Ile and Asn, which are highly conserved in the HSP60 family, might be related with the epitope recognized by 3C8. In contrast, it was also demonstrated that three amino acids of Leu, Gly and Val, which are not well conserved in the HSP60 family, might be related to the epitope recognized by 5C3.
BACKGROUND: Although several epidural catheterizations in small animals have been reported, all of them were performed surgically and no percutaneous method has been reported. We have established a technique for percutaneous chronic epidural catheterization in rabbits. METHODS: Following pentobarbital anesthesia, the animals (n = 15) were fixed in a prone position using a fixing apparatus. A 19-gauge Tuohy needle was inserted in the lumbar region at an angle of about 30 degrees to the skin with the paramedian approach and advanced into the epidural space with the loss-of-resistance method. A 23-gauge Nylon catheter was advanced cephalad in the epidural space and the distal tip was extruded from the neck following the subcutaneous tunnelling. The effects of 0.5 ml of 1% lidocaine injected through the catheter were observed for 10 days. RESULTS: No behavioral or neurological abnormalities were observed after the catheterization except for one case of catheterization in the epidural vessel. Motor paralysis of hind-limbs became manifest at 1-2 min after injection of 0.5 ml of 1% lidocaine through the catheter, and lasted 15-25 min. Autopsy revealed that the catheter was located in the lumbar epidural space in all animals and the distribution of methylene blue was consistent with that of lidocaine. CONCLUSION: This rabbit model can be used to investigate the effects of epidurally administered drugs.
We found that the catabolism of nicotinamide (Nam) differs due to an intake of Nam itself in rats. When rats were fed with a Nam-free, tryptophan-limiting diet, the major catabolite of niacin was N1-methyl-4-pyridone-3-carboxamide (4-Py). However, its percentage was changed with increasing the intake of Nam. The major metabolite was N1-methylnicotinamide (MNA) in the diet containing 0.006% Nam, or 0.1% Nam. The toxicity of excess Nam was observed when rats were fed with a 0.5% Nam-containing diet. In this diet, the major metabolite was Nam N-oxide and it was noted that the urinary excretion of nicotinic acid and its metabolite nicotinuric acid was observed. Therefore, these acids might be detected only when the toxicity of Nam appears.
Since the xylosidase of Bacillus pumilus hydrolyzed 1-naphthyl-beta-D-xylopyranoside (naphthyl-X) to produce xylose and 1-naphthol and a chromogenic azo compound is produced by coupling 1-naphthol and Fast Blue Salt B, a simple method for detection of xylosidase activity in single colonies was studied. Escherichia coli JM109 carrying the xylosidase gene of B. pumilus was cultivated at 37 degrees C for 18 h on a LB plate containing 0.5 mg/ml naphthyl-X, and then the plate was overlaid with 3 ml of a top layer containing 24 mg of agar and 6 mg of Fast Blue Salt B. After incubation of the plate at 37 degrees C for 1 h, each colony became reddish-brown. Even a small colony with xylosidase on the plate was easily distinguished from colonies without the enzyme.
We investigated the relative activity of N-(beta-D-glucopyranosyl)-nicotinic acid as a niacin nutrient in rats and in Lactobacillus plantarum ATCC 8014. N-(beta-D-Glucopyranosyl)-nicotinic acid is a detoxified product or storage form of nicotinic acid that is found in plants. The relative activity of N-(beta-D-glucopyranosyl)nicotinic acid to nicotinic acid in rats was 1/2.3, 1/2.2, 1/1.0, and 1/1.7 as indices of the body weight gain, food intake, blood NAD content, and the increased urinary excretion of niacin and its metabolites, respectively. N-(beta-D-Glucopyranosyl)nicotinic acid had no niacin activity in Lactobacillus plantarum ATCC 8014.
We measured xylanase activities upon eight chromogenic substrates, o- or p-nitrophenyl-beta-D-xylopyranoside (oNP-X or pNP-X) and o- or p-nitrophenyl-beta-D-xylooligosaccharides (oNP-Xn or pNP-Xn, n = 2-4), and studied for their uses as substrates in a kinetic study. The Kcat and K(m) of Bacillus pumilus xylanase (EC 3.2.1.8) activities for pNP-X2 were 0.24s-1 and 0.5 mM, respectively. The relative xylanase activities with the other substrates to that with pNP-X2, pNP-X3, pNP-X4, oNP-X, oNP-X2, oNP-X3, and oNP-X4 were < 0.001, 9.4, 9.7, < 0.001, 19, 190, and 200, respectively. HPLC analysis of the digestion products of oNP-X2 or pNP-X2 showed that the xylanase hydrolyzed each of the substrates only at the ether bond between nitrophenol and xylobiose. All ether bonds of pNP-X3, oNP-X3, pNP-X4, or oNP-X4 were hydrolyzed by the xylanase and further hydrolyses proceeded in the digestion products, e.g., oNP-X2 and oNP-X3 from oNP-X4. Therefore, oNP-X2 was screened as a useful substrate in a kinetic study of the xylanase. The K(m) and Kcat of the xylanase for oNP-X2 were 0.38 mM 2.29s-1, respectively. Thermodynamic studies showed that the higher reaction rate obtained with oNP-X2 than that with pNP-X2 was due to a significant decrease in the activation energy change, despite a decrease in the activation entropy change.
PURPOSE: To detect intravitreal peroxides in vivo by a new fluorophotometric method with a hydrogen peroxide (H2O2)-sensitive fluorescent dye. METHODS: The authors used a 2',7'-dichlorofluorescin (DCFH) assay to measure oxidative status in the rabbit vitreous. In the presence of H2O2 and lipid hydroperoxides, nonfluorescent DCFH in the vitreous is oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF; excitation, 495 nm; emission, 520 nm) that is detectable by fluorophotometry. Reactions of DCFH with various concentrations of H2O2 were investigated in vitro and in vivo. An inhibitory effect of catalase also was monitored. Vitreous fluorophotometry with DCFH was performed immediately and at 3, 7, and 28 days after constant light exposure to the retina (1800 lux, 24 hours) as an oxidative stress. RESULTS: In vitro study revealed that H2O2 oxidized DCFH to DCF in a dose-dependent manner, ranging from 0.1 to 100 mmol/1 in concentration. Catalase inhibited DCF production. Vitreous fluorophotometry demonstrated that H2O2 oxidized DCFH to DCF in vivo in a dose-dependent manner, ranging from 0.06 to 60 mmol/1 in concentration. DCF production in the vitreous significantly increased immediately (P = 0.03) and at 3 days (P = 0.01) and 7 days (P = 0.01) after light exposure, and it returned to the pretreatment level by day 28. CONCLUSIONS: The results suggest that this fluorophotometric method quantitatively can detect intravitreal peroxides in vivo. This method will be helpful to study the oxidative status in some experimental pathologic conditions.
An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in 81-adult T-cell leukemia/lymphoma (ATLL) patients in a multi-institutional cooperative study. Complete remission and partial remission was achieved in 29 (35.8%) and 31 (38.3%) patients, respectively. The median survival of all patients was 8.5 months with a predicted 3 year survival of 13.5% by the Kaplan-Meier method. The median duration of response was 7.5 months and 13 patients are alive during a maximum observation period of 44.7 months. The median survival time was 29.1 months. Multivariate analysis using the proportional hazards model revealed hypoproteinemia, high GPT and thrombocytopenia as poor prognostic factors. In 42.5% of courses white blood cell (WBC) nadirs were less than 0.5 x 10(9)/l. Days required for the recovery of WBC from the nadir were less than 5 days in 64.2% of the treatment courses. The G-CSF-supported intensified chemotherapy regimen for ATLL yielded a better response rate and longer survival compared to previous reports in Japan. As duration of remission is still short, further studies of postremission therapy or other strategies are warranted.