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Biomedical subjects

H Nishi

Publications and source records attributed to H Nishi.

At least 73 records · Page 4Linked to original sources
PubMed1997

Chromatography of crotamiton and its application to the determination of active ingredients in ointments.

Crotamiton, which is a mixture of cis and trans isomers, was investigated by several separation techniques. One of the HPLC modes, in which crotamiton eluted as a single peak, was selected for the determination of five active ingredients (crotamiton, prednisolone, glycyrrhetinic acid, dibucaine and chlorhexidine hydrochloride) in an ointment. The simultaneous determination was performed using isocratic reversed-phase mode within 20 min by employing an octyl (C8) column and a mobile phase containing sodium dodecyl sulfate (SDS) and 2-propanol. The method was successfully applied to quality control and stability testing of the ointment.

Antipruritics↗
PubMed1997

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

Actins↗
PubMed1997

Decreased renal accumulation of biotinylated chimeric monoclonal antibody-neocarzinostatin conjugate after administration of avidin.

Murine monoclonal antibodies (mAbs) such as A7 administered to humans induce a human anti-mouse antibody response. Moreover, because Fab fragments of mAbs are able to penetrate target tumors easily, they may be more suitable than intact mAb to be carriers of anticancer agents such as neocarzinostatin (NCS), which are rapidly inactivated in the blood. To address these problems, chimeric A7 Fab fragment-NCS conjugate (chA7Fab-NCS) was produced. However, large amounts of 125I-labeled chA7Fab-NCS accumulate in the kidney and can lead to renal dysfunction. To decrease renal accumulation of chA7Fab-NCS, chA7Fab was biotinylated and administered with a subsequent injection of avidin. Human pancreatic carcinoma-bearing nude mice were injected with 125I-labeled biotinylated chA7Fab-NCS with or without subsequent administration of avidin. The accumulation of 125I-labeled biotinylated chA7Fab-NCS in tissue samples was measured at appropriate time intervals. 125I-labeled biotinylated chA7Fab-NCS was cleared more rapidly from the blood and the kidney with the administration of avidin than without it. There was no difference between tumor accumulation in these groups. The tumor/blood ratio of radioactivity of 125I-labeled biotinylated chA7Fab-NCS was significantly higher with subsequent administration of avidin than without avidin. The administration of biotinylated chA7Fab-NCS followed by avidin may enhance safety and permit the administration of larger doses of NCS without the subsequent development of renal failure. A larger amount of 125I-labeled biotinylated chA7Fab-NCS was retained in the liver and spleen with the subsequent administration of avidin than without avidin.

Adenocarcinoma↗
PubMed1997

Analysis for the subcellular distribution of oligonucleotide/lipid complexes.

We synthesized a lipoglutamide having tetraethylene glycol tails (PEG lipid), and prepared a DNA/PEG lipid complex. Observation by a confocal laser scanning fluorescence microscope showed that the oligonucleotide/PEG lipid complex distributed in cytoplasmic region. On the other hand, a oligonucleotide/lipofectin complex distributed in nucleus. Interactions of the oligonucleotide complexes with isolated nucleus were also investigated, and mechanisms of the subcellular distributions were discussed.

Animals↗
PubMed1996

Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat.

STUDY DESIGN: This study was designed to evaluate whether allografts of intervertebral disc materials produce hyperalgesia in the rat and whether an immune response, pH, or chemicals correlate with the induced hyperalgesia. OBJECTIVE: To elucidate the pathomechanisms of radicular pain secondary to lumbar disc herniation. SUMMARY OF BACKGROUND DATA: It has been reported that a low pH, an autoimmune reaction, or chemical radiculitis is likely responsible for radicular pain associated with lumbar disc herniation. In animal studies, it has been shown that hyperalgesia (an increased sensitivity to painful stimuli) involves activation of phospholipase A2 and nitric oxide synthase. METHODS: Fat, nucleus pulposus, and anulus fibrosus were allografted into the epidural space at L6 in the rat. Withdrawal response thresholds to mechanical stimuli and withdrawal response latencies to thermal stimuli on the tail and pH in the applied tissues were measured after surgery. Interleukin-1, phospholipase A2, and nitric oxide synthase were examined in the applied tissues using immunohistochemistry, nicotineamide adenine dinucleotide phosphate-diaphorase histochemistry, and in situ hybridization. RESULTS: Allografted fat did not produce hyperalgesia. Allografts of nucleus pulposus and nucleus pulposus plus anulus fibrosis showed evidence of mechanical and thermal hyperalgesia, respectively. There were no observed changes in pH over time. Although interleukin-1 was demonstrated in all applied tissues, phospholipase A2 was only observed around the applied nucleus A2 was only observed around the applied nucleus pulposus and nucleus pulposus plus anulus fibrosus. Nitric oxide synthase was only markedly increased around the applied tissues. CONCLUSION: The nucleus pulposus and anulus fibrosus produce different forms of hyperalgesia (mechanical vs. thermal) associated with different and distinct immunohistochemical changes. It is possible that radicular pain of a lumbar disc herniation results from chemicals, such as phospholipase A2 and nitric oxide.

Adipose Tissue↗
PubMed1996

Enantiomer separation of drugs by electrokinetic chromatography.

This review surveys the enantiomer separation of drugs by electrokinetic chromatography (EKC). EKC is one option of capillary electrophoretic (CE) techniques, which permits the separation of electrically neutral drugs. In enantiomer separation by EKC, ionic pseudo-stationary phases such as chiral micelles and proteins, which can migrate with its electrophoretic mobility and can interact with the solutes, are employed as chiral selectors. Addition of electrically neutral chiral selectors such as cyclodextrins and precolumn conversion of solutes into diastereomers are also successful in EKC. A brief theory of separation and modes of EKC enantiomer separation are described with some typical applications.

Chromatography↗
PubMed1996

Enantiomer separation of basic drugs by capillary electrophoresis using ionic and neutral polysaccharides as chiral selectors.

The enantiomer separation of basic drugs by capillary electrophoresis was investigated employing two types of polysaccharides as chiral selectors. One type consists of electrically neutral polysaccharides such as dextran and dextrin, in which the separation mode is capillary zone electrophoresis (CZE), and ionic drugs are suitable for this mode. The other consists of ionic polysaccharides such as chondroitin sulfate C. Chondroitin sulfates are known as mucopolysaccharides and natural components, being charged, linear, sulfated polysaccharides of high mass. Therefore, the latter approach can be classified as affinity electrokinetic chromatography (AEKC). Both ionic and neutral drugs can be separated by AEKC owing to its separation principle. The separation of enantiomers of some basic drugs such as diltiazem and trimetoquinol was investigated with both CZE and AEKC employing polysaccharides as mentioned above and the enantioselectivity was compared. A brief mechanism of enantiorecognition by polysaccharides is also described.

Chondroitin Sulfates↗
PubMed1996

Micellar electrokinetic chromatography perspectives in drug analysis.

Micellar electrokinetic chromatography (MEKC) has become a popular mode among several capillary electromigration techniques. Most drug analyses can be performed by using MEKC because of its wide applicability. Enantiomer separation, separation of closely related peptides and isotopic compounds, separation of very complex mixtures, determination of drugs in the biological samples, etc., can be successfully achieved by MEKC. This review surveys typical applications of MEKC analysis. Recent advances in MEKC, especially with pseudo-stationary phases, are described. Modes of electrokinetic chromatography including MEKC, a separation theory of MEKC and selectivity manipulation in MEKC are also briefly mentioned.

Body Fluids↗
PubMed1996

Polyclonal B cell chronic lymphoproliferative disease with hairy cell morphology: a case report and clonal studies.

We describe a patient who has a chronic polyclonal B lymphocyte proliferation with a hairy-cell appearance. A 48-year-old Japanese woman with marked splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to out hospital. Laboratory examination revealed marked polyclonal IgG hypergammaglobulinemia. Morphologic examination of the patient's peripheral blood, including May-Giemsa staining and scanning electron microscopy, showed a monotonous proliferation of hairy-appearing mature lymphocytes. An immunophenotypic study revealed an expansion of cells with mature B cell antigens positive for CD11c; however, light-chain restriction was not seen. The lack of both immuno-globulin heavy-chain and T cell receptor gene rearrangements by Southern blot analysis indicated the polyclonal nature of the proliferating B cells. This was confirmed further by a clonal analysis of the patient's lymphocytes using an X-chromosome-linked restriction fragment polymorphism within the X-linked phosphoglycerate kinase (PGK) gene. Since chronic B cell lymphoproliferation with a hairy cell appearance has not been described previously, this case might be extremely rare, and has important implication for the pathogenesis of mature B cell lymphoproliferative diseases, including hairy cell leukemia.

B-Lymphocytes↗
PubMed1996

Applicability of monoclonal antibody Fab fragments as a carrier of neocarzinostatin in targeting chemotherapy.

Two types of fragments of MAb A7 were produced to improve the efficacy and safety in targeting chemotherapy with neocarzinostatin. In this study, 125I-labeled F(ab')2 and Fab fragments of MAb A7 and 125I-labeled MAb A7 were injected intravenously into mice with pancreatic carcinoma xenografts, and the accumulation of each antibody in the tumors was compared. A greater amount of the 125I-labeled Fab fragments of MAb A7 localized in the tumor 2 h following the injection than was observed with the other probes. Relatively less 125I-labeled MAb A7 localized in the tumor 2 h following the injection than was observed with the other two probes. Moreover, reaction of rabbit antimouse IgC with the Fc portion, which is the most immunopotent region of the Fab and F(ab')2 fragments of MAb A7 and MAb A7, was determined by ELISA; the weakest reaction was observed with the Fab fragments of MAb A7. These results suggest that the Fab fragments of MAb A7 may be more suitable carriers of an anticancer drug that is inactivated rapidly in the blood, such as NCS, in targeting chemotherapy than either intact MAb A7 or the F(ab')2 fragments of MAb A7.

Animals↗
PubMed1996

DNA typing of HLA class II genes in Japanese patients with rheumatic heart disease.

To study further the association between HLA and rheumatic valvular disease, DNA typing HLA class II genes (DRB1, DQA1, DQB1 and DPB1) was performed in 72 unrelated Japanese patients with predominant mitral stenosis and 525 unrelated Japanese healthy controls, based on the polymerase chain reaction in combination of dot-blot hybridization with sequence-specific oligonucleotide probes. As compared with controls. Patients with mitral stenosis showed increased frequencies of DQA1*0104 (18.1% v 7.2%; RR = 2.82, P = 0.002, Pc = 0.03) and DQB1*05031 (13.9% v 4.8%: RR = 3.23, P = 0.002, Pc = 0.05). In contrast, no significant deviation in the frequencies of DRB1, DPA1 or DPB1 alleles was observed in the patients. These observations suggest that the susceptibility to mitral stenosis is in part controlled by a gene (or genes) in close linkage disequilibrium with HLA-DQA1*0104 and DQB1*05031, i.e. the susceptibility gene may be mapped within the HLA-DQ region.

Adult↗
PubMed1996

Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene.

Introduction of molecular genetics has improved our understanding of HCM substantially, but has simultaneously raised further important questions. Studies on HCM are revealing a more complex picture than might have been expected on clinical grounds. Further extensive studies are warranted to elucidate the pathogenesis and pathophysiology of HCM, and to establish therapeutic strategies to cure or prevent the development of the disease.

Adult↗
PubMed1996

Effects of neocarzinostatin-chimeric Fab conjugates on the growth of human pancreatic carcinoma xenografts.

Neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of MAb A7 (chA7Fab) directed against human pancreatic carcinoma. The anti-tumour effect of chA7Fab-NCS was tested in a nude mouse model on pancreatic carcinoma and compared with A7-NCS or NCS alone. The anti-tumour effect of chA7Fab-NCS increased in a dose-dependent manner and was significantly greater than either A7-NCS or NCS. Tumour growth was completely suppressed after the administration of chA7Fab-NCS. An enzyme-linked immunosorbent assay with rabbit anti-mouse immunoglobulin was performed to examine the antigenicity of chA7Fab. ChA7Fab had less reactivity with rabbit anti-mouse immunoglobulin than either whole antibody A7 or murine Fab fragments of A7. Thus, chA7Fab-NCS can inhibit human pancreatic cancer growth in an animal and may be useful for targeting chemotherapy to pancreatic cancer in humans.

Animals↗
PubMed1996

Distribution of neocarzinostatin conjugated to biotinylated chimeric monoclonal antibody Fab fragments after administration of avidin.

We have developed chimeric Fab fragments of MAb A7 (chA7Fab) and have reported on their potential usefulness as a carrier of neocarzinostatin (NCS). However, a large amount of chA7Fab accumulates in the kidneys which might cause renal failure. This was one of the major side-effects of the chA7Fab-NCS immunoconjugate administered to humans. To decrease the kidney accumulation of chA7Fab, chA7Fab was biotinylated and administered with a subsequent injection of avidin to nude mice with pancreatic cancer. The accumulation of biotinylated chA7Fab in the blood and the kidneys decreased significantly after the injection of avidin. In a separate experiment with biotinylated chA7Fab-NCS, the blood and kidney accumulation decreased significantly after the injection of avidin. These findings suggest that the injection of biotinylated chA7Fab complexed with NCS followed by avidin may be safer and may permit the administration of larger doses of NCS without the subsequent development of renal failure.

Animals↗
PubMed1996

[Diagnosis and targeting therapy of colorectal cancer using antibody].

Application of monoclonal antibody for diagnosis and therapy of colorectal cancer was reviewed. The history and present status of radioimmunoimaging of cancer were presented. Immuno-guided surgery using radiolabeled antibody and hand-aided detector during surgery is a promising approach for complete excision of cancerous region. Also, a new antibody labeling method using a micro-magnet instead of radioisotopes may lead to a new era in immunodiagnosis of cancer. Finally, immunotargeting chemotherapy using antibody-anticancer drug conjugates was reviewed. A new type of immunoconjugate composed of human/mouse chimeric antibody and Neocarzinostatin seems to be one of the most promising drug formulas for immunotargeting chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1996

[A case of gastrointestinal bleeding from metastatic alveolar soft part sarcoma of the jejunum].

Alveolar soft part sarcoma (ASPS) is a rare malignant tumor. It is often seen in the extremities of youngsters, and frequently metastasizes to the lung, brain, and bones. We experienced a case of ASPS which presented with gastrointestinal (GI)bleeding and was diagnosed as metasatic ASPS of the jejunum. We could not find in the literature a single case of ASPS which metastasized to the intestine and caused GI bleeding. We feel that it is important to consider the possibility that metastasis to the intestine can cause GI bleeding in a patient with a history of ASPS.

Adult↗
PubMed1995

Enantiomeric separation of drugs by mucopolysaccharide-mediated electrokinetic chromatography.

Chondroitin sulfate C (sodium salt) and heparin (sodium salt), which are both mucopolysaccharides and natural components, have been employed as chiral selectors in electrokinetic chromatography (EKC) for the separation of enantiomers of drugs. These additives are charged, linear, sulfated polysaccharides having large mass. Ionic and hydrophobic interactions are probably the bases for the separation. Among tested drugs that are electrically neutral or basic, trimetoquinol, diltiazem, and their related compounds were successfully enantioseparated by EKC with mucopolysaccharides, especially with chondroitin sulfate C. The choices of pH and the concentration of mucopolysaccharides were found to be important for improvement of enantioselectivity. The acidic buffer solutions were effective for enantioseparation of the solutes in the chondroitin sulfate C system, although no migration of the basic drugs was observed in the heparin system. The results were compared with the enantiomeric separation by EKC with dextran sulfate (sodium salt). The method using chondroitin sulfate C was successfully applied to the optical purity testing of the drug substances.

Chromatography↗