Structure of triphosphonoglycosphingolipid containing N-acetylgalactosamine 6-O-2-aminoethylphosphonate in the nervous system of Aplysia kurodai.
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Biomedical subjects
Publications and source records attributed to S Abe.
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A recombinant soluble form (sEPO-R) of erythropoietin (EPO) receptor (EPO-R) was produced by Chinese hamster ovary cells and isolated in high yield with the EPO-fixed gel. Ligand binding assays were done using three methods; precipitation of sEPO-R radiolabeled EPO complex and competition of sEPO-R for the binding of radiolabeled EPO with the cellular EPO-R. The results showed a Kd of 17 nM which was much lower than those for cellular EPO-R. One N-glycosylation site exists in sEPO-R but the glycosylation did not affect the binding affinity to EPO. A complex with a molecular size that corresponded to a 1:1 complex of EPO and sEPO-R was detected.
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BACKGROUND: The value of nucleolar organizer regions (NOR) visualized by silver staining (AgNOR) for the histologic differentiation, pathologic staging, and estimation of growth rate was assessed by the investigation of paraffin sections from 58 lung adenocarcinomas. AgNOR consist of NOR-associated proteins, and the number of AgNOR might be related to proliferative activity. METHODS: In lung adenocarcinoma, the growth rate can be measured by means of chest radiographs. Using this technique, the authors studied the correlation between the mean number of AgNOR and growth rate. RESULTS: The mean number of AgNOR ranged from 1.8 to 6.3 (mean +/- standard deviation, 4.0 +/- 0.8). Neither the degree of histologic differentiation nor the pathologic staging was related to the AgNOR count. The tumor growth rate was estimated on the basis of the doubling time in the chest radiographs of 13 patients. The doubling time ranged from 80 to 760 days. There was a high inverse correlation between the AgNOR count and the doubling time (r = -0.910; P less than 0.001). CONCLUSIONS: Thus, it appears to be possible to use the mean number of AgNOR as an index of proliferative activity.
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Arginine deiminase (EC 3.5.3.6) was purified to homogeneity from the cell extract of Mycoplasma arginini by molecular-sieve, anion-exchange and arginine-affinity chromatographies. The purified enzyme was composed of 2 identical sub-units with a molecular weight of 45.000 and had a pI of 4.7. Its Vmax value and Km value for L-arginine were estimated to be 50 units/mg protein and 0.2 mM, respectively. It exerted maximal enzyme activity at pH 6.0-7.5 and at 50 degrees C. The arginine deiminase was stable at neutral pH. When injected i.v. into mice, the half-life of the arginine deiminase in blood was about 4 hr. In culture, the enzyme strongly inhibited the growth of 6 kinds of mouse tumor cell lines by depleting L-arginine in the culture media. When the in vivo growth-inhibitory activity of arginine deiminase was tested for the 6 tumor cell lines, i.p. administration of the purified enzyme effectively prolonged the survival time of the mice injected with all kinds of the tumor cell lines. Especially, the in vivo growth of a hepatoma cell line, MH134, was completely prevented by the daily administration at a dose of 0.2 mg/mouse for 14 days. These results raise the possibility of the use of the arginine deiminase derived from Mycoplasma arginini as a new anti-tumor drug.
BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) can infect a number of cells of different lineages in vitro, yet the immunophenotypes of most adult T-cell leukemia/lymphomas (ATLs) are restricted to CD4+. The apparent discrepancy between these findings is still largely unknown. PURPOSE: We report on a unique case of ATL in which the leukemia cells were positive for both T-cell and myeloid cell antigens. To characterize these cells, we isolated cell lines from this patient with ATL. METHODS: The fresh leukemia cells were cultured without the addition of interleukin-2. Cell cloning was carried out by limiting dilution. RESULTS: A cell line (MU) and its clonal sublines were established. MU cells showed the same chromosomal abnormalities and T-cell receptor beta-chain gene rearrangement pattern as those of fresh leukemia cells. MU cells were exclusively positive for a myeloid cell marker (CD13) but not for T-cell markers, despite the presence of T-cell receptor gene rearrangement. CONCLUSION: The established ATL cell line showed both T-cell and myeloid cell characteristics, which seems to be the first evidence for the close association of ATL cells with both lymphoid and myeloid features. The cell line may provide a new insight for the targets of HTLV-1 infection and transformation in vivo.
Karyotypes of 107 cases with adult T-cell leukemia/lymphoma (58 male, 49 female; 81 acute or lymphoma type, 26 chronic or smoldering type) were reviewed by a panel of cytogeneticists and were correlated with the subtypes of the disease. Clonal chromosome abnormalities were found in 103 (96%) cases, of which four had hypotetraploidy. Of 184 numerical abnormalities in the remaining 99 cases with near- or pseudodiploidy, trisomies for chromosomes 3 (21% of cases), 7 (10%), and 21 (9%), monosomy for X chromosome (38%) in the female, and loss of a Y chromosome (17%) in the male were more frequent than expected (P less than 0.01). Of 373 structural abnormalities in all the 103 aneuploid cases, translocations involving 14q32 (28%) or 14q11 (14%) and deletion of 6q (23%) were most frequent, followed by deletion of 10p (9%), 3q (8%), 5q, 9q, and 13q (7% each), and 1p and 7p (6% each). The proportion of cases with aneuploid clones (with greater than or less than 46 chromosomes), the average numbers per case of both numerical and structural abnormalities, and marker chromosomes were larger in the aggressive acute or lymphoma type than in the nonaggressive chronic or smoldering type (P less than 0.01). The combination of rearrangement in 14q32 and monosomy X (seven cases) or deletion of 10p (six cases), and that of trisomy 3 and deletion in 6q21 (six cases), occurred only in the acute or lymphoma type and may be associated with the aggressiveness in adult T-cell leukemia/lymphoma.
To assess the accuracy of the bronchoscopic DNA content analysis, samples of non-small-cell lung carcinomas (NSCLC) were investigated by means of flow cytometry. Samples were dissociated using the detergent Triton X-100. In 58 NSCLC cases, 39 (67%) had DNA aneuploid tumors. We compared the DNA indices of bronchoscopic brushing samples with 21 corresponding surgical samples. In 16 (76%) cases, DNA ploidy of both bronchoscopic and surgical samples were in concordance. In 3 (14%) cases, both bronchoscopic and surgical sample showed DNA aneuploidy, but the number of the DNA aneuploid stem cell lines was different. The cause of these differences was ascribed to the intratumor DNA heterogeneity. In 2 (10%) cases, the bronchoscopic sample showed DNA diploidy, but the surgical sample showed DNA aneuploidy. In these cases, tumor cells obtained by bronchoscopic brushing were so few that the small DNA aneuploid peak was undetectable in the DNA histogram. But the tumor DNA ploidy was evaluated correctly in 90% of 21 cases using bronchoscopic samples. Consequently, despite some drawbacks, the DNA ploidy diagnosis using bronchoscopic samples in this relatively small study, was almost as reliable as surgical samples.
Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect. In normal mice, ubenimex prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors. Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice. These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections.
A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
Two patients with von Willebrand's syndrome had intraocular hemorrhages without trauma or neovascularization. A 13-year-old Japanese girl complained of sudden spotted vision in her left eye. Vitreous, peripapillary retinal, and subretinal hemorrhages were seen by ophthalmoscopy in the affected eye. In addition, a 19-year-old Japanese man had repeated vitreous hemorrhage and epistaxis. Also noted was gyrate atrophy of the choroid and retina. Analysis of the coagulation-fibrinolysis system revealed decreased activities of Factor VIII and von Willebrand's factor in both patients. The amount of von Willebrand's factor antigen also was decreased. These results suggested that the patients had von Willebrand's syndrome. The bleeding tendency in the disorder appeared to be responsible for the pathogenesis of the intraocular hemorrhages seen in these patients.
IT has been proposed that iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is an agent for myocardial fatty acid metabolism in animal models. The aim of the present study was to determine whether alterations in fatty acid uptake and/or utilization in patients with hypertrophic cardiomyopathy (HCM) could be detected by 123I-BMIPP. Myocardial imaging with 123I-BMIPP and thallium-201 (201Tl) was performed in 14 fasted patients. A dose of 111 MBq of 123I-BMIPP was administered intravenously at rest, and myocardial emission computed tomography was obtained 20 min and 3 h after injection. The 201Tl imaging was also performed within 1 week after the 123I-BMIPP study. The regional myocardial uptake and clearance of 123I-BMIPP and 201Tl were assessed quantitatively. The myocardial distribution of 123I-BMIPP was more heterogeneous than that of 201Tl in patients with HCM. The myocardial uptake of 123I-BMIPP was lower in the anteroseptal region of the left ventricle than in the posterolateral region (74% vs. 85%, P less than 0.001). The anteroseptal wall showed a faster clearance of 123I-BMIPP than the posterolateral wall (33% vs. 27%, P less than 0.01). Both a decreased uptake and rapid clearance of 123I-BMIPP were observed in the hypertrophied myocardium of the anteroseptal wall, where 201Tl uptake was normal or even increased. Myocardial segments with a markedly increased thickness showed a lower uptake and faster clearance of 123I-BMIPP than those with mild hypertrophy (uptake 73% vs. 82%, P less than 0.05; clearance 30% vs. 25%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
We isolated three glial fibrillary acidic protein (GFAP) cDNA clones from a glioma cell line, U-251 MG. One clone isolated from a U-251 MG cDNA library was long, but lacked both ends. Using poly(A)+ RNA and primers synthesized according to the sequence of this clone, we used the polymerase chain reaction-assisted rapid amplification of cDNA ends (PCR-RACE) method, which is a strategy to isolate cDNA ends, and obtained cDNA clones for the 5' and 3' ends. From the sequences of these overlapping clones, the complete nucleotide sequence of human GFAP cDNA was established. The start (ATG) and the stop (TGA) signals were seen at nucleotide positions 15 and 1311, respectively, and divided the entire sequence of 3027 bp into 14 bp of 5' non-coding, 1296 bp of coding and 1717 bp of 3' non-coding regions. Using cDNA probes made from both the coding and the 3' non-coding regions, Northern blot hybridization was performed with two different stringencies on RNAs from human and rodent brains and human GFAP-positive and -negative cells. It was shown that the 3' non-coding region probe was more specific for human GFAP than the coding region probe which was specific only under higher stringency conditions. This was also suggested by homology analysis of the sequence with those of various intermediate filament proteins. Based on these findings, we performed spot blot hybridization of sorted human chromosomes and Southern blot hybridization of PCR-amplified DNAs of a panel of hamster-human somatic cell hybrids and localized the human GFAP gene to chromosome 17.
Lansoprazole is a newly developed proton pump inhibitor. The purpose of this study was to determine whether morning or evening dosage gave better control of 24-hr intragastric pH. In this study, we examined the antisecretory effect of lansoprazole by repeated intragastric pH monitoring on four occasions in eight normal subjects and compared median 24-hr pH values and pH threshold time of pH greater than or equal to 4 between morning and evening dosing, following the administration of lansoprazole 30 mg once daily in either the morning or evening for seven days. Intragastric pH was monitored before and after seven days of treatment. Both morning and evening dosing caused a rise in the intragastric pH. Median pH for 24 hr was 4.3 and 1.6 with and without lansoprazole morning dosing and 4.6 and 2.1 for evening dosing, respectively. The pH threshold curve shifted to the right with lansoprazole treatment in either case. However, no differences were found between morning and evening dosing in terms of median 24-hr pH values or pH threshold time of pH greater than or equal to 4. These results indicate that lansoprazole can be given once daily in either the morning or evening because of its potent and long-lasting antisecretory activity.
Takayasu arteritis is a non-specific chronic inflammatory vascular disease of unknown etiology. Since the incidence of this disease in the child-bearing years is relatively high, the management of pregnancies with this disease is of great importance in clinical obstetrics. This study is aimed at discussing the maternal management and obstetrical outcome, based on the clinical data obtained from 23 pregnancies of 15 patients treated in our hospital in the past 12 years. Since the disease was in the active state, artificial abortions were conducted in four cases in the 1st trimester of pregnancy. Among the remaining 16 cases, 3, who exhibited neither hypertension nor other complications, vaginally delivered neonates weighing 2,660-3,100 g with Apgar scores of nine after 37 weeks' gestation. C-sections were performed for 13 patients who showed sustained hypertension or/and developed other vascular disorders. Their gestational periods ranged from 34 to 40 weeks and the body weight of the infants varied from 1,425 to 3,024 g. No adverse influence of pregnancy and delivery on Takayasu arteritis was detected in the puerperium of any patients. It is suggested that the state of Takayasu arteritis in early pregnancy and the magnitude of blood pressure elevation in the late gestational period are the most critical and definitive factors in determining the management of pregnancy of a patient with Takayasu arteritis. Cooperative managements by the specialists in obstetrics, internal medicine, and perinatology are required to provide a satisfactory clinical outcome.
A single photon emission computed tomography (SPECT) with 201Tl chloride (Tl-201) was carried out prospectively in 50 patients with pulmonary nodules and its diagnostic value was compared with those of 67Ga citrate (Ga-67) and 99mTc-labeled hexamethylpropyleneamine-oxime (Tc-99m-HMPAO). Tl-201 SPECT provided 88% (early)-91% (delayed) sensitivity, 85% (early and delayed) specificity and 87% (early)-89% (delayed) accuracy. The sensitivity of the Tl-201 planar image was 56 (early)-62% (delayed), which was significantly lower than that of SPECT. Delayed SPECT images at 2 hour postinjection were more preferable to disclose the malignant pulmonary nodule than early SPECT images at 15 minutes postinjection. The application of SPECT with Ga-67 failed to improve the sensitivity of planar imaging for malignant pulmonary nodules. Tc-99m-HMPAO was concentrated in 62% of 13 patients with malignant pulmonary nodules, which was slightly higher than Ga-67 in 54% of 28 patients. In an analysis of the histologic types of lung cancer, the sensitivity of Tl-201 was not significantly different in all types. On the other hand, Ga-67 was positive only in 25% of 12 patients with adenocarcinoma. A combination of SPECT and Tl-201 is the best choice among routine scintigraphic techniques for depicting malignant pulmonary nodules. The Tl-201 SPECT image may play a complementary role in the characterization of pulmonary nodules which are revealed on a plain radiograph and computed tomography.
Synthesis of surface-functionalized, probe-containing latex nanospheres is described. Approximately 40,000 probe ions may be encapsulated in a nanosphere of 50 nm diameter. The probe may be a radionuclide or a lanthanide with long-lived fluorescence. Alternatively, a "cargo" of pharmaceutical interest may be used. The surface of each nanosphere contains thousands of acid groups which may be functionalized for subsequent attachment to biomolecules such as antibodies. Functionalized nanospheres have been successfully coupled to a tobacco virus.