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Biomedical subjects

A Ando

Publications and source records attributed to A Ando.

At least 217 records · Page 12Linked to original sources
PubMed1990

Synthesis of fluorine analogues of protoporphyrin potentially useful for diagnosis and therapy of tumors.

With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogues of protoporphyrin, in which the vinyl group(s) were replaced by difluorovinyl group(s), were synthesized by the reaction of the formylporphyrins with sodium chlorodifluoroacetate in the presence of triphenylphosphine. Some improvements in the reported procedures for the synthesis of formylporphyrins are also described. Preliminary results of biological tests of the products showed that 8(2),8(2)-difluoroprotoporphyrin accumulates to gastric cancer more selectively than other fluorine analogues and that 3(2),3(2),8(2),8(2)-tetrafluoroprotoporphyrin is taken up by rat hepatoma cells more readily than the others.

Animals↗
PubMed1990

Biodistribution of 95Nb and 182Ta in tumor-bearing animals and mechanisms for accumulation in tumor and liver.

The biodistribution and binding substances of 95Nb and 182Ta were investigated and compared with other nuclides using tumor-bearing rats and mice. Retention values of 95Nb in tumor tissue were greater than those for 67Ga-citrate, while those for 182Ta were similar to those for 67Ga. The values for these nuclides in the liver and spleen were much smaller than those for 67Ga. However, the values for blood and some soft tissues were much greater than those for 67Ga. The concentrations of 95Nb and 182Ta were more dominant in the connective tissue (especially inflammatory tissue) than in the other categories of tumor tissue. These nuclides accumulated rapidly into the mitochondrial fraction (containing lysosome) of the liver, reaching about 50% after 48 hours, but these nuclides existed relatively uniformly in the tumor cells. The main binding substance of these nuclides in the above tissues was the acid mucopolysaccharide whose molecular mass exceeded 40,000 daltons. Radioactive niobium can be a potential tumor imaging agent. Among radioactive niobiums, 95mNb has physical characteristics (half-life 90 hours, IT decay, 234-keV energy of 100% abundance) suitable for clinical imaging study.

Animals↗
PubMed1990

Tumor uptake and biodistribution of various radiolabels.

42K, 86Rb, 134Cs and 201Tl accumulated in viable tumor tissue and not in necrotic tumor tissue. 22Na, however, accumulated in necrotic tumor tissue. These elements existed almost as free ions in the tissues. The ions of 67Ga, 111In, 169Yb and 167Tm, which are hard acids, were predominant in connective tissue (especially inflammatory tissue) rather than in viable tumor tissue and were not seen in necrotic tumor tissue. These ions were bound to the acid mucopolysaccharide with a molecular weight of about 10,000 dalton in tumor and other soft tissues. The ions of 46Sc, 51Cr, 103Ru, 95Zr, 181Hf, 95Nb, 182Ta and 58Co, which have incomplete d-shells, were much more dominant in connective tissue (especially inflammatory tissue) than in viable and necrotic tumor tissue. They tended to accumulate into the lysosome of malignant tumor cells. They were bound to the acid mucopolysaccharides whose molecular weights exceed 40,000 dalton. The ions of 65Zn and 103Pd, which are soft acids, mainly accumulated in viable tumor tissue.

Animals↗
PubMed1990

Mapping of the HLA-D region by pulsed-field gel electrophoresis: size variation in the DQ-DR interval.

Pulsed field gel electrophoresis (PFGE) was used to construct genomic maps of different HLA-D region haplotypes. In the course of these experiments a new HLA class II beta chain sequence, DV beta, was located close to DX alpha between DX alpha and DQ beta. All other markers studied, from the DP, DZ/DO, DQ and DR subregions, were consistent in their positions in the haplotypes studied but the distance between DQ alpha and DR alpha differed in various haplotypes. For example, in DR7 (MANN) this distance was approximately 380 kb, but in the DR2 haplotype (AKIBA), it was 270 kb. This may be due to variations, either in the number of duplicated DRB genes or in the length of other uncharted DNA, in the HLA-D region.

DNA Probes↗
PubMed1990

Crohn's disease in the Japanese is associated with the HLA-DRw53.

The association of Crohn's disease (CD) with the HLA system was investigated in Japanese patients by serological and genomic methods. HLA antigens were typed in 30 unrelated Japanese patients with CD and 54 healthy controls. The frequencies of HLA-DR4, DRw53 and DQw3 antigens were increased in CD (76.7, 86.7 and 80.0%) compared with controls [37.0%, p corrected (pc) = 0.007; 52.9%, pc = 0.001; 52.0%, pc = 0.009]. DQw7 and DQw8 antigens, the new split antigens of DQw3 produced by the TA10 antibody and linked to the DR4 and DRw53 antigens, were not significantly different in the DQw3-positive CD and controls. Class I antigens were not significantly different in the CD and controls. HLA-DR-B and DQ-B probes were used to study PstI-generated restriction fragment length polymorphism (RFLP) in CD and controls. The DRw53-specific PstI DR-B 2.6-kb fragment was increased in CD (88.0%) compared with controls (37.5%, pc = 5.6 X 10(-4)). The PstI DR-B 3.2-kb fragment was also increased in CD (80.0%) compared with controls (35.0%, pc = 5.6 X 10(-3)). It is reasonable to infer that the DRw53 is the most important susceptibility antigen in Japanese CD. The subtypes of the DR4 were determined by the hybridization of the DQ-B probe. The DQ-B PstI fragment patterns were not different in CD and controls.

Biomarkers↗
PubMed1989

Influence of vitamin B2 on formation of chromium(V), alkali-labile sites, and lethality of sodium chromate(VI) in Chinese hamster V-79 cells.

The effect of vitamin B2 on the cellular reduction and cytotoxicity of chromate(VI) was studied using Chinese hamster V-79 cells. Electron spin resonance studies showed that incubation of cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complex and that cellular pretreatment with riboflavin (Vitamin B2) for 24 h prior to exposure increased the level of chromium(V) complex, but the level of chromium(III) remained unchanged. Analysis of flavin derivatives revealed that pretreatment with vitamin B2 increased free riboflavin without altering flavin adenine dinucleotide and flavin mononucleotide. In addition, the level of the flavoenzyme glutathione reductase, which is capable of reducing chromate, was unaffected by pretreatment with vitamin B2. However, treatment of cells with vitamin B2 and Na2CrO4 augmented the inhibition of glutathione reductase attributable to Na2CrO4 alone. Using a colony-forming assay, pretreatment with vitamin B2 resulted in a decrease of cytotoxicity after exposure to the lethal concentration of chromate (15 microM) but did not affect the cytotoxicity at sublethal concentration of this metal (5-7.5 microM). Alkaline elution studies demonstrated that Na2CrO4 induced alkali-labile sites in the DNA of cells in a concentration-dependent manner (5-15 microM) and pretreatment with vitamin B2 resulted in an increase of these DNA lesions at all concentrations of Na2CrO4. The results, showing that vitamin B2 enhances chromate-induced alkali-labile lesions and chromium inhibition of glutathione reductase, might be due to an increase of chromium(V) species, possibly through its ability to directly reduce chromium(VI). The results also suggest that the extent of DNA lesions induced by chromate may not correlate directly with the cytotoxic effects of this metal.

Animals↗
PubMed1989

Vitamin B2-enhancement of sodium chromate (VI)--Induced DNA single strand breaks: ESR study of the action of vitamin B2.

Incubation of Chinese hamster V-79 cells with Na2CrO4 plus vitamin B2 resulted in an increase of Na2CrO4-induced DNA single strand breaks. Electron spin resonance (ESR) studies showed that vitamin B2 enhanced the formation of both hydroxyl radical and tetraperoxochromate (V) during the reaction of Na2CrO4 with hydrogen peroxide. Furthermore, ESR studies demonstrated that a chromium (V) species with a g value of 1.977 was formed by the reaction of Na2CrO4 with vitamin B2. These results indicate that chromate reacts with vitamin B2 to form chromium (V) species and also suggest that the enhancement effect of vitamin B2 on chromate-induced DNA single strand breaks may result from an increase of chromium (V)-related hydroxyl radical formation.

Animals↗
PubMed1989

Analysis of gene structure and antigen determinants of DR2 antigens using DR gene transfer into mouse L cells.

Three HLA class II DR beta genes and one DR alpha gene from the DR2 haplotype were cloned in cosmid vectors. The DR beta II gene might be a pseudogene lacking the first exon that encodes the leader peptide. The DR beta I and DR beta III genes were expressed, together with the DR alpha-chain, after transfection into mouse L cells. Restriction enzyme mapping of the DR beta genomic clones and reactivity of their products expressed on the L cell transfectant against mAb showed that the DR beta I and DR beta III genes encoded the nonpolymorphic and polymorphic DR beta chain, respectively. This arrangement is the reverse of that observed in other haplotypes, such as DR3, 4 and 6. The alignment of the HLA class II genes including the DR beta genes on the chromosome 6, however, was consistent with other haplotypes, e.g., centromere-DX beta-DX alpha-DV beta-DQ beta-DQ alpha-DR beta I-DR beta II- DR beta III-DR alpha-telomere. These results suggest that the susceptibility to mutations or gene conversions responsible for genetic polymorphisms depends on the gene itself and not on its location. Furthermore, absorption experiments of anti-DR2 allosera by the DR alpha/DR beta transfectants revealed that the so-called DR2 specificities were determined by multiple epitopes although both the DR beta I and DR beta III genes behaved similarly with DR2-specific antibodies.

Absorption↗
PubMed1989

Mapping and nucleotide sequence of a new HLA class II light chain gene, DQB3.

A genomic clone specifying a new HLA class II antigen beta chain, DQB3, was isolated from a human genomic phage library using a DQB1 cDNA probe under low stringency conditions. Southern hybridization and nucleotide sequence analyses identified the beta 2 domain exon (exon 3) with several deleterious mutations and the CP-TM-CY exon [connecting peptide, transmembrane, and cytoplasmic regions, (exon 4)], but the first, second, and fifth exons encoding the 5' UT-leader, the beta 1 domain, and the 3' UT domain of normal beta chains, respectively, were entirely missing. The nucleotide sequences of these two exons were distinct from those of other class II beta chain genes, but slightly more related to the DQB1 and DQB2 genes than to other class II genes. The DQB3 sequence mapped between DQA2 and DQB1, 15 kb upstream from DQA2, by analysis of overlapping cosmid clones. This mapping was supported by the fact that Taq I, Msp I, and Bam HI DQB3 polymorphisms were perfectly correlated with the DQA2 polymorphism and not with any polymorphisms in the DR or DQ subregion, suggesting the presence of a hot spot for recombination between DQB3 and DQB1.

Amino Acid Sequence↗
PubMed1989

No difference in the nucleotide sequence of the DQ beta beta 1 domain between narcoleptic and healthy individuals with DR2,Dw2.

Narcolepsy is a sleep disorder completely associated with HLA-DR2,Dw2. We demonstrated the 100% presence of three DQ beta fragments (EcoRI 2.4-kb, BamHI 2.9-kb, and PstI 12-kb) in narcoleptic patients that were detected in healthy DR2 controls only at decreased frequencies. In this paper, we have cloned the DQ beta gene from three Japanese narcoleptic patients and sequenced their beta 1 domain in order to study the sequence polymorphisms that might exist in the DQ beta genes of patients, but no difference in sequence could be found between narcoleptic and healthy individuals, suggesting that narcolepsy is not due to mutation in the DQ beta gene. In this context, a possible role of the HLA class II antigens in narcolepsy is discussed.

Base Sequence↗
PubMed1989

HLA-D typing of heterozygotes using restriction fragment length polymorphism in the HLA-DQ gene region on the basis of standard band patterns derived from HLA homozygotes.

Genomic DNAs from 37 Epstein-Barr virus-transformed HLA-D homozygous cell lines with different Dw specificities, Dw1-Dw23, and DKT2 were digested with four different restriction endonucleases (EcoRI, PstI, TaqI, and MspI) and hybridized to DQ alpha and DQ beta cDNA probes. Polymorphic patterns of multiple fragments correlating with Dw, DQ, and DR haplotypes were detected, and the restriction fragment length polymorphism standard pattern specific for each Dw, DQ, and DR specificity could be defined. The polymorphic fragment patterns of HLA-D heterozygotes were predicted simply by the summation of two standard patterns of HLA-D homozygotes and utilized to identify HLA-D specificities of 25 normal individuals, who are HLA heterozygotes in most cases. The HLA-D, -DR, and -DQ specificities defined by this DNA typing were compared with those assigned by serologic and cellular typing. There was good correlation, allowing the application of accurate genotyping by DQ alpha and DQ beta cDNA probes to HLA class II typing of HLA heterozygotes.

Base Sequence↗
PubMed1989

Determination of the lysosomal role in tumor accumulation of 67Ga by dual-tracer studies.

The lysosomal role in tumor accumulation of 67Ga was determined by dual-tracer (67Ga and 46Sc) studies. It became clear that 67Ga essentially did not accumulate in the tumor lysosome, and that the lysosome did not play a major role in tumor accumulation of 67Ga. In addition, it was revealed that tumor lysosome was hardly disrupted at all in some phases of fractionation procedures.

Animals↗
PubMed1989

Relation between the location of elements in the periodic table and various organ-uptake rates.

Fifty four elements and 65 radioactive compounds were examined to determine the organ uptake rates for rats 3, 24 and 48 h after i.v. injection of these compounds. They were prepared as carrier free nuclides, or containing a small amount of stable nuclide. Generally speaking, behaviors of K, Rb, Cs and Tl in all the organs were very similar to one another, but they differed from that of Na. Bivalent hard acids were avidly taken up into bone; therefore, uptake rates in soft tissues were very small. Hard acids of tri-, quadri- and pentavalence which were taken up into the soft tissue organs decreased more slowly from these organs than other ions. Soft acids such as Hg2+ were bound very firmly to the component in the kidney. Anions (with few exceptions), GeCl4 and SbCl3 were rapidly excreted in urine, so that the uptake rates in organs were low.

Animals↗
PubMed1989

Effect of vitamin E on survival, glutathione reductase and formation of chromium (V) in Chinese hamster V-79 cells treated with sodium chromate (VI).

The effect of vitamin E on cytotoxicity induced by Na2CrO4 was evaluated by colony-forming assay using Chinese hamster V-79 cells. Pre-treatment with alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure to Na2CrO4 resulted in a marked decrease in the cytotoxicity caused by this compound. The reduction of chromate-induced cytotoxicity was observed at all concentrations of Na2CrO4 (5-15 microM), and the protective effect increased with higher concentrations of vitamin E (5-25 microM). The level of glutathione reductase activity, which is capable of reducing chromate, was not affected by cellular pre-treatment with vitamin E. However, Na2CrO4 decreased glutathione reductase activity in a concentration-dependent fashion (5-15 microM) and pretreatment with vitamin E resulted in a significant recovery of enzyme activity suppressed by Na2CrO4, suggesting that this enzyme inhibition is linked to the cytotoxicity of this metal. Electron spin resonance studies showed that a paramagnetic chromium (V) complex was formed in cells treated with Na2CrO4, and that cellular pre-treatment with vitamin E reduced the formation of this chromium (V) intermediate. These results indicate that vitamin E protects cells from chromate-induced cytotoxicity as well as from enzyme inhibition, and also suggest that Na2CrO4-induced cytotoxicity is mediated by the generation of a reactive intermediate.

Animals↗
PubMed1989

Effects of atrial natriuretic peptide on regional renal blood flow measured by a thermal diffusion technique.

The effects of atrial natriuretic peptide (ANP) on the regional renal blood flow were examined in anesthetized dogs. A thermal diffusion technique was applied in an attempt to observe the intrarenal blood distribution. Tissue blood flow was continuously measured according to the changes of the thermal gradient produced by a semiconductor (Peltier effect). The data (x) obtained by these probes were closely related to those (y) of the ion gas clearance method (the probe for cortical blood flow; y = 1.08x-6.23 r = 0.99, the probe for medullary blood flow; y = 1.00x +0.26 r = 0.99). The basal values of cortical and medullary blood flows measured with the flow probe in anesthetized mongrel dogs were 85 +/- 16 and 55 +/- 9 ml/min/100 g kidney weight, respectively. ANP was infused into renal artery at doses of 0.01 (n = 6), 0.05 (n = 8), 0.3 (n = 6) micrograms/kg/min and the effect on renal hemodynamics and renal excretory functions was observed. The effect was also compared with that of furosemide. Low dose of ANP did not affect renal blood distribution. Intermediate dose of ANP selectively increased medullary blood flow from 46 +/- 8 to 62 +/- 7 ml/min/100 g kidney weight, and higher dose significantly increased both cortical and medullary blood flow. ANP produced diuresis and natriuresis in a dose-dependent manner, which was not necessarily related to the changes of intrarenal blood distribution. Furosemide did not affect the renal hemodynamics. Several parameters of renal functions such as lithium and free water clearances, showed changes different from those with ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗