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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 631 records · Page 35Linked to original sources

IL-5 induces a Pgp-1 (CD44) bright B cell subpopulation that is highly enriched in proliferative and Ig secretory activity and binds to hyaluronate.

Pgp-1 expression was examined in unstimulated B cell populations and in B cells activated with several polyclonal stimuli. Flow cytometry analysis demonstrated that Pgp-1 expression increased when B cells were activated with supernatant of cloned Th2 cells, with LPS, or with IL-5, stimuli that induced polyclonal proliferation and differentiation. IL-5-primed B cells were phenotypically unique and could be divided into two distinct subpopulations based on the brightness of Pgp-1 expression. Furthermore, sterile sorting experiments showed that proliferating and differentiating B cells were highly enriched in a Pgp-1-bright, Ia-dull, B220-dull subpopulation. The possibility that Pgp-1 expressed on activated B cells functions as an adhesion molecule was evaluated by assessing adhesion of activated B cells to defined substrates. It was found that IL-5-activated B cells bound strongly to hyaluronate-coated surface, and this binding was specifically inhibited by anti-Pgp-1 Ab. These findings suggest that Pgp-1 expression is a useful marker which, under defined conditions, identifies the proliferating and differentiating subset of activated B cells. Moreover, the Pgp-1 bright subset of IL-5-primed B cells binds to hyaluronate in a Pgp-1-dependent manner that suggests a potential role of Pgp-1 in the in vivo adherence and trafficking of activated B cells.

Animals↗

Single-strand-binding factor(s) which interact with ARS1 of Saccharomyces cerevisiae.

Since plasmids containing autonomously replicating sequence(s) (ARS) can transform Saccharomyces cerevisiae cells at high frequency, ARS are considered to be the replication origins of chromosomes. To study the mechanism of initiation of eukaryotic chromosomal replication, we examined protein factors which interact with the ARS1 region located near the centromere of chromosome IV in S. cerevisiae. Using the gel-shift assay, we found protein factors which bound to a single-stranded, 97-bp fragment of the ARS1 region containing the core consensus. Competition experiments with various oligodeoxyribonucleotides (oligos) suggest that a site recognized by the factor(s) was within the element containing the core consensus and adjacent close matches to the core consensus of the minus strand. Indeed, when the oligo containing the minus strand of this element was used as a probe, two oligo-protein complexes were detected. Mutations in the core consensus reduced these binding activities. When the plus-strand oligo of the same region was used as a probe, a retarded band was also detected, but with less specific binding. Considering the fact that the core consensus and close matches to the core consensus are important for ARS function, these results imply that the protein factors detected in this experiment may participate in DNA replication.

Base Sequence↗

Translocation between chromosomes 8q24 and 14q11 in T-cell acute lymphoblastic leukemia.

Cytogenetic study was performed on a patient with T-cell acute lymphoblastic leukemia (T-ALL). It revealed a chromosomal translocation between chromosome bands 8q24 and 14q11. 8q24 is known to encode the oncogene c-myc, while 14q11 encodes the genes for T-cell receptor-alpha (TCR-alpha) and T-cell receptor-delta (TCR-delta). Therefore, this chromosomal translocation t(8;14) (q24;q11) seemed to be unique and specific to T-cell malignancy.

Adult↗

Effect of food and antacid on absorption of orally administered ticlopidine hydrochloride.

Ticlopidine is a potent inhibitor of platelet aggregation. Absorption of ticlopidine after oral dosing is rapid and complete. Ticlopidine is extensively metabolized with a relative minor component of unchanged ticlopidine in plasma. The randomized crossover study described here was undertaken to examine the effect of food and antacid on the oral bioavailability of a single dose of ticlopidine (250 mg) in normal volunteers. After postprandial treatment the rate and extent of absorption of ticlopidine was earlier and greater relative to fasting treatment [tmax = 1.71 +/- 0.33 hr (fed) vs 1.92 +/- 0.56 hr (fasting) and AUC0-infinity = 2.164 +/- 0.813 micrograms X hr/mL (fed) vs 1.808 +/- 1.052 micrograms X hr/mL (fasting)]. The oral bioavailability of ticlopidine was increased by 20% when taken after a meal. In contrast, absorption of ticlopidine administered after antacid treatment was approximately 20% lower than under fasting conditions. Administration of ticlopidine with food is recommended to maximize gastrointestinal tolerance.

Administration, Oral↗

Clonal origin of mammalian hepatitis B virus-related hepatocellular carcinoma.

The clonal origins of 20 multifocal hepatocellular carcinomas (HCCs) in four woodchucks were analyzed by the Southern blot hybridization technique. The woodchucks were divided into two groups according to the morphological classification of multifocal tumors: 1) three woodchucks had multifocal tumors that were widely separated and similar in size, which suggests a multiclonal origin of the tumors; and 2) one woodchuck had ten small multifocal tumors surrounding two large main tumors, which indicated intrahepatic metastasis from an original tumor. Results from the first group demonstrated that the number of integrated woodchuck hepatitis virus (WHV) DNAs differed from tumor to tumor, and none of the bands were the same size. In the second group, eight of the ten small tumors surrounding the two large tumors showed the same pattern of WHV DNA integration. One demonstrated an additional band and also shared the same bands with the other tumors, and one small tumor had a different pattern of integration from the others. It was concluded that the clone dissimilarity demonstrated by hybridization patterns does not necessarily mean that HCCs originate independently from different clones, because genetic changes may occur after or at the time of metastasis.

Animals↗

Reappraisal of bronchial arterial infusion therapy for advanced lung cancer.

As preoperative adjuvant therapy for advanced lung cancer, bronchial arterial infusion (BAI) of a chemotherapeutic agent was administered to patients with stage IIIa and IIIb hilar lung cancer. The infusion modality was changed for each term, from a single drug infusion, to a two drug infusion and then a three drug infusion, and the combination of infused drugs was selected in accordance with cell types. A significant radiographic shrinkage was observed after BAI therapy by the single, two and three drug infusions, being noted as 40.7 per cent, 61.8 per cent and 83.9 per cent, respectively. The effect on squamous cell carcinoma was more prominent than on other cell types. Upon microscopic examination of the resected specimens, significant histo-pathological effects were observed in 57.7 per cent of the patients who received single or two drug infusions, while the rate increased to as high as 92.2 per cent in the patients who received the three drug infusion. The histological effects of BAI therapy were also most marked in squamous cell carcinoma. It is of special interest that 5 of the 10 patients who received the three drug infusion of Carboquone (CQ) + Mitomycin C (MMC) + Nimustine-HCL (ACNU) for squamous cell carcinoma, showed complete disappearance of viable cancer cells at the tumor site; something which was never observed after the single and two drug infusions. It was therefore concluded that BAI therapy for advanced lung cancer should be reappraised through the modification of infusion methods.

Adenocarcinoma↗

Hepadnavirus enhancer and its binding proteins.

In the hepadnavirus enhancer region, a 33 bp DNA sequence is strongly conserved among mammalian hepadnavirus genomes. To elucidate the role of the sequence, we tested enhancer activities and capability to form DNA-protein complex of several synthetic DNAs. Not only two tandem copies of a 46 bp DNA covering the sequence but also two tandem copies of a 23 bp in the sequence exhibit enhancer activity. Also the activity was augmented by treatment of a tumor promoter, TPA. DNA binding proteins complexes with the 23 bp DNA were augmented in extracts of HepG2 or HeLa cells stimulated with TPA. These results imply that the conserved sequence of hepadnavirus enhancer is a TPA-inducible enhancer which is transactivated by ubiquitous DNA-binding proteins. We presented results showing that DNA-protein complexes with a 23 bp DNA are similar to but distinct from those with a TPA-responsive element DNA, the recognition site for c-jun/fos products. We also presented results suggesting that hepadnavirus X protein may not directly or indirectly affect DNA-protein complex formation with the conserved sequence in the hepadnavirus enhancer.

Base Sequence↗

Thyroid peroxidase in endemic goiter tissue.

Thyroid peroxidase (TPO) activity and TPO protein were analyzed in endemic goiter tissue under iodine deficiency and after iodine supplement. TPO was prepared from 9 endemic goiter tissues and 4 normal thyroid tissues by solubilizing enzyme with detergent. Four patients with endemic goiter received iodized oil injection 12 months before surgery. All patients had normal serum thyrotropin (TSH) and thyroid hormone levels before surgery. TPO activity was measured by iodinase assay and guaiacol assay. Endemic goiter TPO showed greater iodination activity than that of normal TPO (p less than 0.01). The guaiacol assay showed greater TPO activity in 6 of the 9 endemic goiter tissues than that of the normal tissue. Iodized oil treatment did not affect TPO activity or TPO proteins when compared with those in untreated endemic goiter tissues. TPO activity in endemic goiter tissue correlated with thyroid T4 5'-deiodinase activity and not with thyroid hormone content in thyroglobulin. Since thyroid T4 5'-deiodinase and TPO are under control of TSH, an increase in TPO activity in the presence of normal serum TSH may be explained by the increased sensitivity of endemic goiter tissue to TSH-one of the possible adaptation mechanisms of endemic goiter.

Adult↗

Strategies for asymptomatic microscopic hematuria: a prospective study of 1,034 patients.

To establish strategies for treatment of asymptomatic microscopic hematuria we conducted a prospective study of 1,034 patients with this disease. The patients were examined by cystoscopy, urine cytology, abdominal ultrasound and excretory urography. On initial examination 30 highly significant lesions, including 24 cases of urological malignancies, 195 moderately significant lesions and 246 insignificant lesions were detected. In the remaining 563 patients no underlying lesion could be found. Of the 246 patients with insignificant lesions and 563 with unexplained asymptomatic microscopic hematuria followup was done in 421 at 6-month intervals for more than 1 year. A diagnosis became clear within 3 years in 22 patients, including 3 cases of bladder carcinoma and 1 of prostatic carcinoma.

Aged↗

Intrapatient comparison of acute hemodynamic, hormonal, and natriuretic responses to captopril versus enalapril in liver cirrhosis.

We compared acute hemodynamic, hormonal, and natriuretic responses to a single oral dose of captopril (50 mg) versus enalapril maleate (10 mg) administered to eight patients with biopsy-proved liver cirrhosis. Although the two angiotensin-converting enzyme (ACE) inhibitors lowered (p less than 0.05) blood pressure with no change in heart rate during the early postdose period, captopril produced a greater (p less than 0.05) hypotensive effect than did enalapril. Enalapril caused a greater (p less than 0.01 to 0.05) ACE inhibition than did captopril during the 2- to 48-hour postdose period. Plasma renin activity increased (p less than 0.05) with the two drugs and returned toward baseline by 12 hours after administration. Plasma aldosterone levels, elevated before drug administration, were decreased by the two drugs in a stepwise fashion, but the suppressive effect was greater (p less than 0.01 or p less than 0.05) after captopril than after enalapril. Natriuresis was greater (p less than 0.05) during the first 24-hour period after enalapril than after captopril. The findings indicate that the acute pharmacodynamic responses to the two ACE inhibitors differ in patients with liver cirrhosis. However, the mechanism(s) of the divergent effects of the two drugs and the clinical implications remain obscure from this single-dose study.

Adult↗

Effect of salvianolic acid A, a depside from roots of Salvia miltiorrhiza, on gastric H+,K(+)-ATPase.

Salvianolic acid A, a depside from the roots of Salvia miltiorrhiza, inhibited pig gastric H+,K(+)-ATPase and pNPPase with 50% inhibition values (IC50) of 5.2 x 10(-7) M and 1.7 x 10(-6) M, respectively. Kinetic studies revealed that the inhibition patterns induced by salvianolic acid A were competitive with respect to ATP and noncompetitive with respect to K+. Salvianolic acid A (25 mg/kg, i.p.) significantly inhibited acid secretion in pylorus-ligated rats. At the same dose it also showed a significant reduction in the formation of gastric lesion induced by water immersion and restraint stress. These results suggest that salvianolic acid A shows antisecretory and antiulcer activity by inhibiting the gastric H+,K(+)-ATPase.

Adenosine Triphosphatases↗

Recovery of voluntary movement in hemiplegic patients. Correlation with degenerative shrinkage of the cerebral peduncles in CT images.

The severity of the disorder of voluntary movement in 89 chronic hemiparetic patients was correlated with the degenerative reduction of descending fibres evaluated by the magnitude of the shrinkage of the cerebral peduncles (CP) in computed tomographic (CT) images. The severity of hemiplegic posture and motor disturbance in the proximal and distal muscles was related to the total amount of residual descending fibres in the CP. In all patients whose CPs were less than 60% of the normal size, recovery from disturbance in reaching and grasping movements and impairment of relative independent finger movements was incomplete. Recovery of these movements occurred when more than 60% of the CP was spared and the degree of recovery from motor weakness was positively correlated with the quantity of intact fibres spared (residual CP ratio). The ability to perform fine and discrete movements with the fingers, known to be an essential function of the pyramidal system, was consistently impaired in patients with severe shrinkage involving the medial division of the CP. There was no particular correlation between the CP shrinkage and neurological signs such as spasticity, hyperreflexia, and pathological reflexes.

Adult↗

Chronic encapsulated intracerebral hematoma associated with cavernous angioma: a case report.

The case of a patient with a chronic encapsulated intracerebral hematoma associated with a cavernous angioma is reported. In spite of a huge space-occupying lesion in the frontal lobe, our patient showed no focal neurological deficit. The clinical picture suggested a slowly growing brain tumor. Intraoperative findings revealed a liquefied intracerebral hematoma with a thick capsule. Pathological investigations demonstrated a capsule rich in neovascularity with a cavernous angioma attached to it. It is presumed that initial bleeding from the cavernous angioma encouraged capsule formation similar to the membrane of chronic subdural hematomas and that repeated bleeding from the capillaries of the capsule allowed the expansion of the hematoma.

Adolescent↗

Lung lavage and surfactant replacement for hydrochloric acid aspiration in rabbits.

Hydrochloric acid (0.1 N, 5.0 ml.kg-1 in total) was administered intratracheally to 28 adult rabbits anesthetized with pentobarbital and mechanically ventilated with pure oxygen. When the PaO2 decreased to 14.1 +/- 2.8 kPa (mean +/- s.d.), the PaCO2 increased to 8.9 +/- 2.5 kPa, and the minute ventilation (VE) decreased to 51 +/- 8% of the baseline value, animals were divided into 4 groups. The deteriorated values did not improve in the non-treated (control) animals, whereas the animals treated with lung lavage and surfactant replacement showed a significant increase in PaO2 to 35.1 +/- 12.2 kPa, and maintained lower PaCO2 and larger VE than the controls. These parameters showed no significant improvement with surfactant replacement alone, and deteriorated further with lung lavage alone. The minimum surface tension (gamma min) of the edema fluid that accumulated in the airways after acid administration was 22.5 +/- 1.7 mN.m-1, and was not lowered by adding surfactant preparation (10 mg.ml-1) whose original gamma min was less than 2 mN.m-1. We concluded that surfactant inhibition by edema fluid was a cause of respiratory failure, and that lung lavage followed by surfactant replacement might be of therapeutic value for acid aspiration.

Animals↗

Dynamics of gastrin-producing cells in the rat after truncal vagotomy. Evaluation by double immunostaining for bromodeoxyuridine and little gastrin.

The mechanism of hyperplasia of gastrin-producing cells (G-cells) in the rat antral mucosa after truncal vagotomy was studied using double immunostaining for bromodeoxyuridine (BrdU) and little gastrin (G17). With single labeling of BrdU, a few G-cells (less than 1%) showed positive immunostaining for BrdU in the nucleus throughout the experimental period in both vagotomized rats and those given a sham operation. The labeled cells in both groups demonstrated a linear increase of BrdU labeling in an identical number of cells for each experimental time-point. The labeling index of the G-cells increased rapidly from day 2 to day 6 and attained a maximum level of 44.0% on day 10 in the vagotomized group after cumulative labeling. Even in this group, however, many G-cells showed no BrdU immunoreactivity throughout the experimental period. These cells did not replicate during the experimental period, but showed an intense reaction product for G17 in their cytoplasm after vagotomy. The present study indicates that the most important factor involved in G-cell hyperplasia observed after truncal vagotomy is the activation of pre-existing G-cells to synthesize and release hormone, together with the rapid maturation of progenitor cells to mature G-cells.

Animals↗

Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi.

Two chalcone derivatives, xanthoangelol (1) and 4-hydroxyderricin (II) isolated from Angelica keiskei Koidzumi, inhibited pig gastric H+, K(+)-ATPase with IC50 values of 1.8 and 3.3 microM, respectively. The inhibition by I or II was competitive with respect to ATP and was non-competitive with respect to K+ I and II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of 1.3 and 3.5 microM, respectively. Proton transport in-vitro was inhibited by I or II, in a dose-dependent manner, 1 at 100 mg kg-1, i.p. significantly inhibited acid secretion and the formation of stress-induced gastric lesions. These results suggest that the antisecretory effect of 1 is due to the inhibition of gastric H+, K(+)-ATPase.

4-Nitrophenylphosphatase↗