Biomedical subjects

T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 343 records · Page 19Linked to original sources

PubMed1998

Purification and characterization of a [3Fe-4S][4Fe-4S] type ferredoxin from hyperthermophilic archaeon, Pyrobaculum islandicum.

A ferredoxin was purified from the hyperthermophilic archaeon, Pyrobaculum islandicum. EPR spectra and metal content analyses suggested that the ferredoxin molecule contained one [3Fe-4S] and one [4Fe-4S] cluster. The ferredoxin was rapidly reduced by 2-oxoglutarate: ferredoxin oxidoreductase purified from P. islandicum, indicating that it functions physiologically as an electron sink for the redox enzymes participating in glycolytic metabolism. Furthermore, the amino acid sequence of the P. islandicum ferredoxin was compared with those of several other bacterial ferredoxins.

Amino Acid Sequence↗

PubMed1998

Detection of several mRNA species in rice phloem sap.

Evidence is reported for the presence of the mRNAs of thioredoxin h, oryzacystatin-I, and actin in the rice phloem sap collected by the insect laser method. As the sieve element, the core component of the phloem, is enucleated, these macromolecules are probably transported from the companion cells.

Actins↗

PubMed1998

Characterization of inhibin/activin subunit, activin receptor, and follistatin messenger ribonucleic acid in human and mouse oocytes: evidence for activin's paracrine signaling from granulosa cells to oocytes.

Inhibin, activin, and follistatin (FS) are gonadal proteins that appear to have a role in regulating folliculogenesis through possible paracrine and/or autocrine interactions. To further examine the potential role of activin in oocyte-granulosa cell communication, we developed a sensitive reverse transcription-polymerase chain reaction protocol to analyze mRNA for the alpha, betaA, and betaB inhibin/activin subunits, FS, and the four activin receptor subtypes in individual human and mouse oocytes. The resulting expression pattern was further compared to that in human cumulus granulosa cells. Our results indicate that neither ssA nor betaB mRNA was detectable in any human or mouse oocyte, that alpha subunit was marginally present in some of the human oocytes, and that FS mRNA was detectable in human but not mouse oocytes. On the other hand, inhibin/activin subunit and FS mRNAs were abundantly expressed in cumulus cells. In addition, mRNAs for all four activin receptor subtypes (ActRIA, ActRIB, ActRIIA, and ActRIIB) were easily detectable in both oocytes and granulosa cells and appeared to be differentially expressed in oocytes during nuclear maturation. Finally, RNAs for both zona pellucida 3 and growth-differentiation factor-9, which were originally used as oocyte-specific markers, were detected in human but not mouse cumulus cells, although at lower levels than observed in oocytes. Taken together with previous studies, these results indicate that oocytes may be capable of responding to, but not synthesizing, activin.

Activin Receptors↗

PubMed1998

Construction of the chimeric reverse transcriptase of simian immunodeficiency virus sensitive to nonnucleoside reverse transcriptase inhibitor.

A number of structurally diverse compounds have been shown to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The compounds can be grouped into two broad classes; nucleoside analogs and nonnucleoside RT inhibitors. The nonnucleoside RT inhibitors are quite specific for HIV-1 RT but not human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) RT. We have investigated the property of SIV/HIV-1 chimeric viruses in which portions of SIV(MAC) RT were exchanged with the corresponding domain of HIV-1 RT; amino acids 176-190, 176-383 and 176-495 of HIV-1 RT. The chimeric virus, which was substituted amino acids 176-190 of RT, had detectable RT activity, and this chimeric RT was sensitive to three nonnucleoside RT inhibitors [nevirapine, HEPT derivative (E-EBU-dM) and TIBO derivative (R82913)]. To further study this chimeric virus, we purified the chimeric RT enzyme expressed in Escherichia coli and determined its kinetic properties; the Km, and Vmax values, and the Ki value of HEPT derivative calculated for the DNA polymerase activity. This study reveals that amino acids 176-190 of SIV(MAC) RT were important for the enzymatic activity and the SIV/HIV-1 chimeric RT, which had amino acids 176-190 of HIV-1, was sensitive to the nonnucleoside RT inhibitor.

Amino Acid Sequence↗

PubMed1998

FK317, a novel substituted dihydrobenzoxazine, exhibits potent antitumor activity against human tumor xenografts in nude mice.

The antitumor effects of FK317, a novel substituted dihydrobenzoxazine, were evaluated using human tumor xenografts (small cell lung cancer, non-small cell lung cancer, stomach cancer, colon cancer, pancreatic cancer, breast cancer, cervical cancer and ovarian cancer). Tumor growth-inhibitory effects and the effective dose-range of FK317 were much stronger and broader, respectively, than those of reference drugs such as mitomycin C, adriamycin, cisplatin, taxol and irinotecan. Furthermore, the body weight decrease and myelosuppression in FK317-treated mice were less than in the animals given any of the reference drugs. To explain this tumor selectivity, the distribution of FK317 was investigated after dosing tumor-bearing mice with the 14C-labelled compound. The concentration of FK317 in tumor tissues was relatively low, and long tumor retention was not observed. However, thin-layer chromatographic separation revealed that the radioactivity in the tumor resided mainly in strongly cytotoxic metabolites, while that in other tissues resided mainly in non-cytotoxic metabolites. These results suggest that FK317 shows strong antitumor activity without side effects, and one reason for this is its specific metabolite pattern. FK317 is now undergoing phase I clinical trials.

Adenocarcinoma↗

PubMed1998

Long-term course of West syndrome associated with tuberous sclerosis.

We retrospectively analyzed the long-term clinical profiles of 47 patients with West syndrome (WS) associated with tuberous sclerosis (TS) the follow-up study for >10 years showed that WS developed into epilepsies of various types in all patients. Their final diagnoses were symptomatic generalized epilepsy (SGE: 29 patients, 62%), symptomatic partial epilepsy (PE: 14 patients, 30%), and undetermined epilepsy (UE: 4 patients, 8%). Eighty-five percent of all patients continued to show the same types of epilepsy that they had at their first examination, but in 15% the diagnosis had to be revised at the end of the follow-up period. The outcome of seizures was unfavorable for the SGE group. In the PE group, however, seizures were controlled in 9 (64%) of the 14 patients, and disturbances of daily activity were mild. In patients with WS associated with TS, the seizure outcome and social activity varied depending on the type of epilepsy or epileptic syndrome that developed from WS. The complicated clinical developments from WS with TS multiple cortical tubers related to epileptogenesis in addition to impairment of brain development.

Adolescent↗

PubMed1998

Porphyromonas gingivalis lipopolysaccharide modulates the responsiveness of human periodontal ligament fibroblasts to platelet-derived growth factor.

Lipopolysaccharides (LPS) prepared from periodontopathic bacteria have been known to induce various biological responses which may lead to periodontal tissue breakdown. The purpose of this study was to determine if Porphyromonas gingivalis LPS could affect cellular functions of human periodontal ligament fibroblasts (HPLF). We showed here the responsiveness of cultured HPLF to platelet-derived growth factor (PDGF)-BB, a growth factor for mesenchymal cells, in the presence of P. gingivalis LPS. DNA synthesis of HPLF was enhanced in a dose-dependent manner when LPS were co-incubated for 48 h; thereafter, it decreased to the baseline level within 24 h incubation. The stimulating effect of PDGF-BB was further enhanced by the pretreatment of HPLF with LPS (10 micrograms/ml) for 48 h. The binding assay of [125I]PDGF-BB and the flow cytometric assay using rabbit antiserum to human PDGF receptor (PDGF-R) beta-type indicated that this enhancement was due to the increase of the number of PDGF-R beta-type on HPLF. Immunoprecipitation using antiserum to human PDGF-R beta-type also showed that the synthesis of PDGF-R beta-type was augmented in the LPS-treated HPLF. These results indicate that P. gingivalis LPS stimulate cellular proliferation and responsiveness to PDGF-BB of cultured HPLF. These cellular reactions may be mediated by PDGF-BB binding, followed by increased synthesis of the receptor protein.

Becaplermin↗

PubMed1998

S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

Animals↗

PubMed1998

The cell cycle-specific growth-inhibitory factor produced by Actinobacillus actinomycetemcomitans is a cytolethal distending toxin.

Actinobacillus actinomycetemcomitans has been shown to produce a soluble cytotoxic factor(s) distinct from leukotoxin. We have identified in A. actinomycetemcomitans Y4 a cluster of genes encoding a cytolethal distending toxin (CDT). This new member of the CDT family is similar to the CDT produced by Haemophilus ducreyi. The CDT from A. actinomycetemcomitans was produced in Escherichia coli and was able to induce cell distension, growth arrest in G2/M phase, nucleus swelling, and chromatin fragmentation in HeLa cells. The three proteins, CDTA, -B and -C, encoded by the cdt locus were all required for toxin activity. Antiserum raised against recombinant CDTC completely inhibited the cytotoxic activity of culture supernatant and cell homogenate fractions of A. actinomycetemcomitans Y4. These results strongly suggest that the CDT is responsible for the cytotoxic activity present in the culture supernatant and cell homogenate fractions of A. actinomycetemcomitans Y4. This CDT is a new putative virulence factor of A. actinomycetemcomitans and may play a role in the pathogenesis of periodontal diseases.

Aggregatibacter actinomycetemcomitans↗

PubMed1998

Comparison of the cariostatic effects between regimens to administer oolong tea polyphenols in SPF rats.

The cariostatic effect of oolong tea polyphenols administered according to several regimens was examined in specific pathogen-free (SPF) Sprague-Dawley rats given both a diet containing 20% sucrose and infected with S. sobrinus 6715. The crude preparation (OTE) of oolong tea polyphenols showed the most prominent effect on caries reduction in SPF rats when OTE was administered in the drinking water beginning 1 day prior to the inoculation of S. sobrinus 6715, when compared with chromatographically isolated polyphenol fractions (OTF1 and OTF6) of OTE. Reduction in caries development was found even when OTE was given 1 day after inoculation of the organism. OTE was shown to significantly inhibit dental caries in rats at the concentrations of either more than 5 microg/ml in drinking water or more than 10 microg/g in diet. OTF1 and OTF6 also showed significant inhibition of caries induction, with the minimum inhibitory concentration of OTF6 being 50 microg/ml in drinking water and the minimum inhibitory concentration of OTF1 being 100 microg/g in diet. These results indicate that cariostatic activity of OTE was effective even after the establishment of S. sobrinus in the oral cavity and was more effective in drinking water than in diet. Furthermore, OTE may contain some anticaries substances that affect the virulence of S. sobrinus other than glucosyltransferases.

Analysis of Variance↗

PubMed1998

Plasma soluble fas and soluble fas ligand in chronic glomerulonephritis.

It has been reported that glomerular cells with apoptosis and positive Fas immunoreactivity are seen in proliferative glomerulonephritis (PGN). Fas induces apoptosis when it binds to Fas ligand (Fas-L) or soluble Fas-L (sFas-L). However, soluble Fas (sFas) blocks apoptosis by inhibiting binding between Fas and Fas-L or sFas-L. That is, Fas, Fas-L, and sFas-L are inducers of apoptosis, but sFas is an inhibitor of apoptosis. We studied the relationship between the plasma levels of sFas and sFas-L in 32 patients with various types of adult chronic glomerulonephritis. Patients with serum creatinine levels >1.5 mg/dl (132.6 micromol/l) were excluded. The plasma levels of sFas-L were within the normal limits in all patients. The plasma levels of sFas in the patients with minimal-change (n = 8) and membranous nephropathy (n = 7) were similar to the age- and sex-matched controls. However, the plasma sFas levels were significantly elevated in patients with mesangial PGN (n = 10) and membranoproliferative glomerulonephritis (n = 7)(3. 4 +/- 0.9 and 3.9 +/- 1.5 ng/ml, respectively) as compared with the age- and sex-matched controls (controls: 2.1 +/- 0.4 and 2.2 +/- 0.6 ng/ml, respectively). In PGN, according to increase of histological grade and decrease of creatinine clearance, the number of TUNEL-positive cells in glomeruli is decreased in spite of an increase of the Fas positivity, and plasma sFas is increased. The degree of proliferative change is determined by the balance between proliferation and apoptosis and/or necrosis. Therefore, increased plasma sFas in PGN may inhibit apoptosis in glomeruli and may be one of the progressing factors in PGN. Thus, we conclude that an increase in plasma sFas levels is important to the protection of apoptosis in PGN.

Adult↗

PubMed1998

A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized to the medial Golgi cisternae.

Small GTP-binding proteins of the Rab family play important roles at defined steps of vesicular transport in protein secretion and the endocytosis pathway. In mammals, more than 30 proteins belonging to the Rab family have been reported to date. We report here the molecular cloning and characterization of a novel Rab protein, Rab33B. The amino acid sequence of Rab33B shows 55.3% identity to the Rab33A protein (previously called S10), and these two proteins share unique amino acid sequences at the effector domain. The genomic organization of rab33B was the same as rab33A: it consists of two exons. Thus, these two proteins make a subclass within the Rab family. Northern blot analysis showed that rab33B is expressed ubiquitously in mouse tissues, in contrast to rab33A whose expression is restricted to the brain and the immune system. A 26 kDa protein was detected by western blotting using a Rab33B-specific monoclonal antibody. Using immunofluorescence studies, Rab33B was shown to co-localize with (alpha)-mannosidase II, a Golgi-specific marker. Immunoelectron microscopy analysis further defined the localization of Rab33B to the medial Golgi cisternae. These results suggest Rab33B plays a role in intra-Golgi transport.

Animals↗

PubMed1998

Expression of heat shock protein after ischemic preconditioning in rabbit hearts.

Previous studies have shown that preconditioning (PC) with a brief ischemic episode induces heat shock protein (HSP) in cardiac tissue. However, it is unclear when and where in the left ventricle HSP is expressed after PC. Hence, the expression of HSP was studied in rabbit hearts at various time intervals after PC using immunohistochemical methods. Rabbits were preconditioned four times with 5 min of occlusion and 5 min of reperfusion of the coronary artery and then were killed at 0, 3, 24, 48, 72 and 168 h after the PC (n=4, for each time interval). Samples were obtained from the subendocardium and subepicardium of the preconditioned and nonpreconditioned wall and these were processed to 4 microm thick cryosections. The sections were immunolabelled with mouse monoclonal IgGs against HSP 72/73. Positive immunoreactivity was observed as early as 3 h after PC, persisting up to 72 h but not detected at 168 h. HSP was expressed not only in the preconditioned myocardium but also in the remote nonpreconditioned myocardium. There was a wide variation in expression among myocytes. Expression was dominant in myocytes compared with vessel walls. It was concluded that PC induced transient and inhomogeneous expression of HSP in rabbit hearts.

Animals↗

PubMed1998

Can POSSUM, a scoring system for perioperative surgical risk, predict postoperative clinical course?

POSSUM, a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, is a scoring system which assesses perioperative surgical risks (Copeland GP et al.: Br J Surg, 1991, Vol 78, 356-360). The POSSUM scoring system consists of two categories of assessment to assess the risk of surgery. A 12-factor (age, cardiac status, pulse rate, systolic blood pressure, respiratory status, Glasgow Coma Score, serum concentration of urea, potassium and sodium, hemoglobin concentration, white cell count and findings on electrocardiography) and 4-grade physiological score (PS) were developed. This was combined with a 6-factor (type of surgical procedure, number of procedures, blood loss, peritoneal soiling, presence of malignancy and mode of surgery) and 4-grade operative severity score (OSS). The present paper attempts to validate it retrospectively. Postoperative hospitalization period and duration of antibiotics administration were both significantly correlated with OSS, but not with PS. These results suggest that the POSSUM scoring system is useful for predicting the postoperative clinical course.

Adult↗

PubMed1998

WA8242A1, A2 and B, novel secretory phospholipase A2 inhibitors produced by Streptomyces violaceusniger. II. Biological properties.

WA8242A1, A2 and B, novel inhibitors of secretory phospholipase A2 (PLA2), were obtained from Streptomyces violaceusniger No. 8242. WA8242B inhibited secretory group I and II PLA2s in a dose-dependent manner. The mode of inhibition of group II PLA2 by WA8242B was in competitive fashion. WA8242B inhibited group II PLA2-induced Prostaglandin I2 (PGI2) production by human umbilical vein endothelial cells. Furthermore, WA8242B was effective in mouse zymosan writhing model.

2-Aminoadipic Acid↗

PubMed1998

[Sick sinus syndrome after chemotherapy for malignant lymphoma with right atrial tumor at initial presentation].

A 56-year-old man was admitted complaining of throat discomfort and dyspnea. He was given a diagnosis of diffuse large B-cell lymphoma on the basis of findings from tumor biopsy specimens of his left pharynx. MRI tomograms and ultrasonic cardiograms revealed a right atrial tumor causing tricuspid stenosis. Although chemotherapy rendered the cardiac tumor indistinct on MRI and UCG images, gallium-67 scintigraphy still demonstrated abnormal cardiac uptake. After 6 courses of CHOP therapy, sick sinus syndrome with syncope suddenly developed in the patient. A cardiac pacemaker was immediately implanted, and radiotherapy was started. The patient's sinus rhythm returned to normal shortly afterward, and the gallium-67 uptake eventually disappeared. In this case gallium-67 scintigraphy was the only diagnostic procedure capable of detecting evidence of residual disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Molecular therapy for human cancer with tumor suppressor p53 gene transfer].

Molecular level approaches have demonstrated that tumor suppressor p53 gene, which is the most commonly mutated gene yet described in human cancers, plays an important role in the pathway of apoptosis triggered by DNA-damaging agents. In addition, defects in apoptosis caused by the inactivation of p53 resulted in resistance to treatment. Human gene therapy has become a reality with the development of effective techniques for delivering the gene to the target cells. These findings suggested a novel approach to cancer therapy with the direct delivery of wild-type p53 gene construct to cancer cells by using an adenoviral vector system. Restoration of wild-type p53 function markedly enhanced the antitumor effect of a common chemotherapeutic agent, cisplatin, in human non-small cell lung cancer cells as well as human colon cancer cells. The application of this technology to human cancer therapy is now in progress.

Apoptosis↗

PubMed1998

[The autopsy case of traumatic carotid artery dissection].

The results of an autopsy of a 78-year-old female patient with an occluded of the right internal carotid artery after a traffic accident are reported. She presented with consciousness disturbance, right conjugate deviation, left hemiparesis and left pathological reflex. Evidence of right skull and clavicular fractures seemed to suggest that severe hyperextension of her neck associated with contralateral lateral flexion had stretched her carotid artery. Although she was treated with antiplatelet therapy, her cerebral swelling due to right global infarction progressed and she died due to bilateral cerebral herniation three days after injury. The autopsy disclosed right dissecting carotid artery occlusion and subadventitial dissection was revealed histologically. When a hematoma dissect the media and adventitia of the carotid artery wall, the outer wall weakens and may dilate without narrowing the lumen of the carotid artery. In this case, the vessel occlusion was considered to be due to a primary intramural hematoma which developed and subsequently ruptured through the intima into the vessel lumen. Early diagnosis and treatment are necessary for improving the prognosis of this disease entity. A patient with poor colateral flow, such as in this case, will show a rapid progression of cerebral infarction. It is best to consider surgical treatment in this case if the other traumatic lesions are able to tolerate surgery.

Aged↗