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H Fukushima

Publications and source records attributed to H Fukushima.

At least 181 records · Page 10Linked to original sources
PubMed1993

Comparison of the effects of KRN2391 and other coronary dilators on porcine isolated coronary arteries of different sizes.

The present study was performed to determine whether KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulphonate), a novel vasodilator, shows different effects on porcine isolated coronary arteries of different sizes. The vasodilating effects of KRN2391 on porcine large (2.5-3.0 mm outer diam.) and small (0.8-1.0 mm) coronary arteries were also compared with those of cromakalim, nicorandil, nifedipine, nitroglycerin and adenosine. The relaxant effects of these drugs were examined in coronary arteries contracted by 25 mM KCl. Nitroglycerin caused greater relaxation in large vessels than in small vessels. In contrast, adenosine, nifedipine and cromakalim caused greater relaxation in small vessels. However, there was no difference between large and small vessels in the relaxing effects of KRN2391 and nicorandil. These unique features of KRN2391 and nicorandil appear to be beneficial in ischaemic heart disease.

Adenosine↗
PubMed1993

Coaggregation of Prevotella intermedia with oral Actinomyces species.

Five strains of Prevotella intermedia were examined for their ability to coaggregate with various gram-positive and gram-negative species of oral bacteria. Two of the P. intermedia strains coaggregated with selected Actinomyces species, P. intermedia 27 with Actinomyces viscosus T14V and Actinomyces naeslundii ATCC 12104, PK606, PK984, and PK947, and P. intermedia 113 with Actinomyces odontolyticus WVU 1546 and Actinomyces israelii WVU 838. Exposure of both Prevotella strains but not the Actinomyces strains to heat, trypsin, or proteinase K abolished most coaggregations. All pairs were disaggregated by the addition of sodium dodecyl sulfate, but only those coaggregations involving P. intermedia 113 were reversed by the addition of 2.0 M urea. P. intermedia 27 was sensitive to periodate oxidation, whereas the partner strains were stable to this treatment. Most coaggregations occurred in the presence of saliva; however, reactions involving P. intermedia 27 were not as strong as those of buffer-suspended cells. Treatment of both P. intermedia 113 coaggregations pairs with proteinase K and the results obtained from suspensions of these pairs in saliva suggest that different surface molecules of this P. intermedia strain may mediate each of these coaggregations. These data suggest that all of these coaggregations involve either a protein or glycoprotein on the Prevotella strain, which may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces strain.

Actinomyces↗
PubMed1993

Differentiation of Yersinia enterocolitica serotype O:5,27 strains by phenotypic and molecular techniques.

Restriction endonuclease analyses of virulence plasmid DNA (REAP) and chromosomal DNA and other phenotypic characteristics were used to study the differentiation of Yersinia enterocolitica serotype O:5,27 strains. There was a close correlation between REAP patterns and the geographical distribution of serotype O:5,27. Human isolates produced only one REAP pattern, which was also found with isolates from pigs and dogs.

Animals↗
PubMed1993

Mechanism of action of KRN2391, a novel vasodilator, in canine mesenteric artery.

The present study was performed to clarify the mechanism of vasodilation of KRN2391 in canine mesenteric artery compared with those of nicorandil and cromakalim. We used the responses of isolated cranial mesenteric artery in vitro and changes in mesenteric blood flow in vivo as indicators reflecting the responses of a conductive artery and resistive arterioles, respectively. In isolated cranial mesenteric artery, KRN2391 (10(-8)-10(-5) M), nicorandil (10(-7)-10(-4) M) and cromakalim (10(-7)-10(-5) M) relaxed contractions caused by 25 mM KCl in a concentration-dependent manner. The concentration-relaxation curve for KRN2391 was shifted to the right by either methylene blue (10(-5) M) or glibenclamide (10(-6) M), but the inhibitory effect of methylene blue was more potent than that of glibenclamide. The concentration-relaxation curve for nicorandil was shifted to the right by methylene blue, but not by glibenclamide. In addition, the curve for cromakalim was shifted to the right by glibenclamide, but not by methylene blue. In in vivo experiments, the injections of KRN2391 (0.3-3 micrograms/kg), nicorandil (10-100 micrograms/kg) or cromakalim (1-10 micrograms/kg) into the mesenteric artery increased mesenteric blood flow in a dose-dependent manner. Glibenclamide (5 mg/kg, i.v.) attenuated the increase in mesenteric blood flow caused by KRN2391, nicorandil and cromakalim, but had no effect on that caused by nifedipine (1 microgram/kg). The ED20 value increased about 4.7-fold for KRN2391, 3.7-fold for nicorandil and 11.5-fold for cromakalim after administration of glibenclamide, as estimated from the % change to the absolute increase in mesenteric blood flow induced by nifedipine (1 microgram/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mechanism of action of KRN2391 in canine coronary vascular bed.

The present studies were performed to clarify the mechanism of action of KRN2391 in various sizes of canine coronary artery. We used the responses of isolated large and small coronary arteries and the changes in coronary blood flow (CBF) as indicators reflecting the responses of conductive arteries and resistive arterioles, respectively. In isolated small coronary artery, the effect of KRN2391 (10(-8)-10(-5) M) was antagonized by either methylene blue or glibenclamide. In isolated large coronary artery, the vasorelaxant effect of KRN2391 (10(-8)-10(-5) M) and nicorandil (10(-7)-10(-4) M) were antagonized by methylene blue (10(-5) M) but not by glibenclamide (10(-6) M). The relaxant effect of cromakalim was antagonized by glibenclamide but not by methylene blue in isolated large coronary artery. Intracoronary arterial injection of KRN2391, nicorandil or cromakalim produced an increase in CBF dose-dependently. Glibenclamide (5 mg/kg, i.v.) attenuated the increase in CBF caused by KRN2391, nicorandil and cromakalim. ED20, the dose that produced an increase in CBF by 20 ml/min, increased about 5-fold for KRN2391 and nicorandil and about 12-fold for cromakalim after administration of glibenclamide. These results suggest that the mechanism of action of KRN2391 and nicorandil depends on the segment of coronary arteries; i.e., they show a nitrate action alone in large coronary artery, and a K-channel opening action in addition to a nitrate action as the size of the coronary artery decreases.

Animals↗
PubMed1993

Effect of KRN2391, a novel vasodilator, on various experimental anginal models in rats.

The antianginal effect of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate, on various anginal models in rats was compared with those of nifedipine and nicorandil. Angina pectoris was induced by methacholine or isoproterenol, and the change in the ST-segments in the electrocardiogram (ECG) was used as the parameter to indicate angina pectoris. The intracoronary administration of methacholine (3 micrograms) produced an elevation in the ST-segment of the ECG. This ST-elevation was inhibited by the intravenous administration of KRN2391 (30 and 100 micrograms/kg), nifedipine (100 and 300 micrograms/kg) and nicorandil (1000 and 3000 micrograms/kg). The administration of isoproterenol (10 micrograms/kg/min, i.v.) produced a depression of the ST-segment of the ECG. The intravenous administration of KRN2391 (100 micrograms/kg), nifedipine (100 micrograms/kg) and nicorandil (3000 micrograms/kg) inhibited the ECG changes induced by isoproterenol. These results suggest that KRN2391 exerts a potent protective effect on angina pectoris models compared with nifedipine and nicorandil. KRN2391 appears to be useful as an antianginal drug.

Angina Pectoris↗
PubMed1993

Association of primary biliary cirrhosis with human leukocyte antigen DPB1*0501 in Japanese patients.

To investigate the relationship between distribution of human leukocyte antigen alleles and susceptibility to primary biliary cirrhosis among Japanese, we performed serological typing and human leukocyte antigen DP genotyping in 47 Japanese patients with primary biliary cirrhosis. Serologically, the frequency of human leukocyte antigen DQ3 was significantly higher in the patients than in healthy controls, whereas frequency of DR52 was significantly lower in the patients. Human leukocyte antigen DP genotyping using the polymerase chain reaction-restriction-fragment-length polymorphism method showed that the frequency of human leukocyte antigen DPB1*0501 (85.1%) was significantly higher in patients than in healthy controls but that the frequency of DPB1*0402 was significantly lower in patients. The positive association of human leukocyte antigen DPB1*0501 with primary biliary cirrhosis was stronger than that of serological human leukocyte antigen DQ3, which can be explained by its linkage to DPB1*0501. In addition, three of seven DPB1*0501-negative patients had DPB1*0202, suggesting that the human leukocyte antigen DPB1 amino-acid chain plays an important role in the immunogenesis of primary biliary cirrhosis among Japanese patients. Comparative analysis of amino acid sequences from DPB1 alleles indicated that a Leu at position 35 of the DPB1 chain likely contributes to the susceptibility to primary biliary cirrhosis among the Japanese.

Adult↗
PubMed1992

Mitochondrial tRNA(Ile) mutation in fatal cardiomyopathy.

A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case.

Adolescent↗
PubMed1992

Enhancement of chemotherapeutic effects by recombinant human granulocyte colony-stimulating factor on implanted mouse bladder cancer cells (MBT-2).

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered intraperitoneally in combination with multidrug chemotherapy using methotrexate (M), vinblastine (V), doxorubicin (A), and cisplatin (C, or for the combination, MVAC) to C3H/He mice (5-week-old females) after experimental carcinoma, MBT-2, a transplantable transitional cell carcinoma of the urinary bladder had been implanted. The effects of therapy were studied. The animal groups consisted of: (1) control (no drug administration), (2) rhG-CSF (100 micrograms/kg/d, from days 8 through 42 after MBT-2 implantation, except for the days when MVAC was administered), (3) high-dose MVAC (2 mg/kg of M, 0.2 mg/kg of V, 2 mg/kg of A, and 4 mg/kg of C once a week for 3 weeks), (4) low-dose MVAC (one-quarter of the high dose), (5) high-dose MVAC with rhG-CSF, and (6) low-dose MVAC with rhG-CSF. In an in vitro system, rhG-CSF did not show any effect on the proliferation of MBT-2 cells or exert any influences on A's tumor proliferation-suppressing action on MBT-2. However, in an in vivo system, concomitant administration of rhG-CSF significantly enhanced the tumor-suppressing effect of the MVAC therapy, as did rhG-CSF alone. The greatest effect was observed in the group receiving high-dose MVAC plus rhG-CSF. These result suggested that rhG-CSF-stimulated granulocytes may exert antitumor activity on tumor cells severely damaged by chemotherapeutic agents at a relatively high concentration. The survival rate was improved to some degree even by administration of rhG-CSF alone. Although further study is required to elucidate the action mechanism of rhG-CSF, these results suggest that rhG-CSF may be useful clinically to enhance the activity of antitumor agents and not only through its ability to alleviate granulocytopenia or prevent its development.

Agranulocytosis↗
PubMed1992

A possible association between basic amino acids of position 13 of DRB1 chains and autoimmune hepatitis.

Fifty-one patients with autoimmune hepatitis have been studied for HLA association by conventional serology and also by modified polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. HLA-DR4 was significantly associated with autoimmune hepatitis (46 of 51 patients, 90.2%). DNA typing of the DRB1 gene for 43 DR4-positive patients by using the PCR-RFLP technique revealed that of 43 patients, 33 had DRB1*0405 (Dw15), five had DRB1*0406 (DwKT2), four had DRB1*0403 (Dw13a), two had DRB1*0401 (Dw4), two of 43 had DRB1*0407 (Dw13b) and one had DRB1*0408 (Dw14b). Thus, there was no significant difference in Dw frequencies between DR4-positive patients and DR4-positive healthy subjects. These findings suggest that the DR4-specific sequence (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain contributes to susceptibility to autoimmune hepatitis among Japanese. Interestingly, all five of the DR4-negative patients had the DR2 specificity (DRB1*1502 or 1601). Taken together, these results imply that the basic amino acids at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), are most important for determining the predisposition to autoimmune hepatitis.

Amino Acid Sequence↗
PubMed1992

Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy.

To elucidate the mechanism of action for intratumoral injection of immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor (TNF) were assayed by immunostaining tissue samples of differentiated thyroid cancer resected with or without presurgical local application of OK-432, a streptococcal preparation. Frozen sections of resected specimens were stained with monoclonal antibodies using either a conventional or a modified immunoperoxidase method. The tumors injected with OK-432 showed increased T lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the non-injected controls. Among these T cells, the CD4+ subset was more numerous than the CD8+ population. In four out of the seven cases constituting the injected group, numerous TNF-positive cells were seen in clusters or lines as well as scattered, while none of the seven cases in the control group was associated with a considerable amount of these cells. In their morphology and distribution pattern, these TNF-positive cells appeared to be of macrophage lineage. Thus local injection of OK-432 in thyroid cancer was shown to recruit T lymphocytes of predominantly the CD4+ subset and to induce in situ production of TNF, a known potent tumoricidal cytokine. The present data warrant further studies in this direction besides wider clinical intratumoral application of the reagent.

Adult↗
PubMed1992

Extensive arterial calcification of unknown etiology in a 29-year-old male.

A 29-year-old male with generalized arterial calcification is presented. The roentgenogram showed extensive calcification bilaterally in the facial, brachial, renal, external iliac, femoral, and popliteal arteries. There was also calcification around the joints of the fingers, toes, elbows, and shoulders. The uniformity of arterial calcification in the radiograph differentiated this lesion from Mönckeberg's arteriosclerosis. The serum concentration levels of calcium, phosphorus, alkaline phosphatase, and calcium regulatory hormones were normal. The patient did not have diabetes mellitus, renal disease, or connective tissue disease, thus the etiology of the calcification was not identified. However, a bone scintigram showed that the uptake of 99 mTc-methylene diphosphate was significantly increased in the calcified arteries. Therefore, increased metabolic activity was associated with the derangement leading to arterial calcification.

Adult↗
PubMed1992

Human insulin-specific immunoglobulin G antibody and hypoglycemic attacks after the injection of gold thioglucose.

A 56-year-old woman with granulomas of gold thioglucose in her hips exhibited recurrent bouts of hypoglycemic attacks. The first attack occurred 2 years after the last injection of gold thioglucose, when large amounts of extractable insulin and human insulin-specific antibody were noted in her serum. Histological examination of the resected granulomas showed marked infiltration of lymphocytes, plasma cells, and macrophages containing yellowish-brown granules, which proved to be gold by electron microscopy using X-ray microanalysis. After resection of the granuloma, however, the frequency of the hypoglycemic attacks decreased remarkably as well as the levels of both extractable insulin and human insulin-specific antibody.

Antibody Specificity↗
PubMed1992

HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients.

To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4 were significantly more frequent in patients with autoimmune hepatitis than in controls. HLA-DR4 was most frequently associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of Dw between the patients and the controls who were DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.

Adult↗
PubMed1992

Structure and sequence of the human alpha-L-fucosidase gene and pseudogene.

Fucosidosis is a rare lysosomal storage disease resulting from a nearly complete deficiency of alpha-L-fucosidase enzyme activity. Previously, cDNA encoding human fucosidase was cloned and sequenced. Here we report the determination of the human fucosidase gene structure and sequence as well as the sequence of the fucosidase pseudogene. The gene encoding fucosidase is composed of eight exons spanning 23 kb of DNA. Analysis of the sequence 5' of the open reading frame indicates the presence of multiple transcription factor binding sites but no TATA box. Northern blot analysis has confirmed an mRNA size of 2.3 kb in human lymphoblasts, testis, and epithelial cells. We have also sequenced the processed pseudogene of fucosidase. The sequence of the pseudogene is 80% identical to that of fucosidase cDNA but does not contain an open reading frame.

Base Sequence↗
PubMed1992

Mitochondrial encephalomyopathies with the mutation of the mitochondrial tRNA(Leu(UUR)) gene.

Four families with mitochondrial encephalomyopathy are described. Probands of three families had typical clinical presentations of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), but the proband of family 4 lacked strokelike episodes. The mitochondrial DNA mutation of tRNA(Leu(UUR)) (transfer ribonucleic acid specific to leucine (UUR codon)) found in MELAS was examined in muscle DNA obtained from biopsy samples of the probands of four families and the maternal relatives of family 2. The mutation was detected in all muscle samples, and the degree of the mutated DNA was 68% to 84% by Southern blot analysis. However, the clinical patterns of the maternal relatives of family 2 were mild and distinctly different from MELAS. The same mutation was also detected in blood-derived DNA samples of all family members examined, including healthy mothers but not fathers, although the degree of mutation did not correlate with the clinical severity. These results confirmed the maternal inheritance of this disease and suggested that the mitochondrial DNA mutation (tRNA(Leu(UUR))) may cause clinical symptoms other than MELAS. The clinical findings of mitochondrial encephalomyopathy should be reinvestigated in terms of the mitochondrial gene mutation; the polymerase chain reaction method will be useful for screening for this mutation of mitochondrial DNA in blood samples.

Acidosis, Lactic↗
PubMed1992

HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific primers.

We previously introduced HLA-DQA1, -DPB1 and DQB1 genotyping with the modified PCR-RFLP method using some informative restriction enzymes which have either a single cleavage site or alternatively no cleavage site in the amplified DNA region, depending on the HLA alleles, making reading of RFLP band patterns much easier. In this study, 43 HLA-DRB1 alleles, excluding DRB1*1103 and *1104 for which no restriction enzymes are available to distinguish each from the other, could be defined by this modified PCR-RFLP method combined with 7 pairs of group-specific primers. It is impossible to distinguish DRB1*0701 and DRB1*0702 as they are identical for the second exon of DRB1. For DR1-DRB1, DR2-DRB1, DR4-DRB1, DR7-DR1, DR9-DRB1, DRw10-DRB1 or DRw52 associated antigens (DR3, w11, w12, w13, w14, and DRw8)-DRB1 gene amplification, the second exon of the DRB1 gene was selectively amplified using each group-specific primer from genomic DNAs of 70 HLA-homozygous B-cell lines and healthy Japanese by PCR. Amplified DNAs were digested with restriction endonucleases and then subjected to electrophoresis assaying simply for cutting, or no cutting, of the DNA, although some alleles can be distinguished only after examination of RFLP band patterns generated and in some cases using double digestion technique with two restriction enzymes. This modified PCR-RFLP method can be successfully applied to all possible DRB1 heterozygotes, despite the fact that 15 pairs of heterozygotes among them cannot be distinguished theoretically by the PCR-SSO method, because the PCR-RFLP method can tell whether two polymorphic sites are linked to each other (cis position) or located on a different chromosome (trans position) by checking the length of RFLP bands generated with double digestion. Thus, the PCR-RFLP method is technically simple, practical and inexpensive for determination of the HLA-DRB1 alleles for routine HLA typing work.

Alleles↗