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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 235 records · Page 13Linked to original sources
PubMed1999

Phosphorothioate G3T4G3 motifs inhibits the early stage of HIV-1 infection.

It is well known that G-rich phosphorothioate oligonucleotides (G-rich PS) bind to the V3 loop of HIV-1 gp120 and inhibit HIV-1 infection. In this study, we investigated the inhibitory mechanism of a new type of G-rich PS (PS-G3T4G3) on the replication cycle of HIV-1. PS-G3T4G3 inhibits both cell to cell and cell free infections. Binding and entry assays revealed that the inhibitory step of PS-G3T4G3 occurs at the early stage of HIV-1 infection. V3 loop-specific mAb test showed that PS-G3T4G3 binds to the V3 loop and prevents its interaction with chemokine receptors. These results suggest that PS-G3T4G3 may be a novel candidate for an HIV-1 inhibitor.

Base Composition↗
PubMed1999

Development of an HIV-1-dependent expression vector with the Cre/loxP system.

Previously, we used the human methionine tRNA promoter as an expression cassette for hammerhead ribozymes. The tRNA promoter driven ribozyme was targeted against the LTR portion of the HIV-1 NL4-3 strain. We constructed VSV-G-pseudotyped MuLV-based vectors expressing the ribozyme. The ribozyme expressing retrovirus vector strongly suppressed gag p24 antigen production in freshly HIV-1 infected MT-4 cells. In this study, the potential of such a molecular genetic intervention was examined by using the Cre-loxP recombination system. Site-specific excision of HIV-1 was achieved by using this model system with an acute infection. These studies represent one step toward the development of a novel antiviral strategy for the treatment of AIDS.

Animals↗
PubMed1999

Diverse glycosylation of MUC1 and MUC2: potential significance in tumor immunity.

Mucins are major epithelial luminal surface proteins and function as a physical and biological barrier protecting mucous epithelia. Diverse glycosylation of mucins potentially provides a basis for tissue-specific interaction with the milieu. When mucins are associated with malignant epithelial cells, they not only protect these cells from a host environment during metastatic dissemination but also generate immunogenic epitopes which are used by the host in the detection and immunological elimination of carcinoma cells potentially depending upon their status of glycosylation. Diverse mucin structures are generated by the combination of different core peptides, of which 10 have been reported so far, multiple types of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (pp-GalNAc-Ts), and the consequences of stepwise glycosylation events. For example, the mucin 1 (MUC1) associated with malignant cells was previously believed to exhibit unique features with a lower percentage of threonine and serine residues attached to N-acetylgalactosamine and/or without extension through core 2 structures. Some of MUC1-specific monoclonal antibodies and cytotoxic lymphocytes recognize the peptide sequences PDTR within the tandem repeat portion exposed by decreased degree of glycosylation. The specific arrangement of N-acetylgalactosamine residues is shown to be generated by a combination of pp-GalNAc-Ts with different specificities. The role of core 2 branching is somewhat confusing because well-known carcinoma-associated carbohydrate epitopes such as sialyl-Le(X), sialyl-Le(a), Le(Y), and others are often expressed when O-glycans are extended through core 2 branching. The other series of well-known carcinoma-associated carbohydrate structures are truncated O-glycans, conventionally called Tn and sialyl-Tn antigens. Interestingly, these are often found to be aligned on core polypeptides, resulting in three or more consecutive truncated O-glycans. MUC2 and other mucins, but not MUC1, have unique tandem repeats containing three or more consecutive serine or threonine residues, which potentially serve as a scaffold for trimeric Tn and sialyl-Tn epitopes. We recently found, using the MUC2 tandem repeat, that trimeric Tn is a high-affinity receptor for a calcium-type lectin expressed on the surface of histiocytic macrophages. The biosynthesis of trimeric Tn was strictly regulated by the acceptor specificity of pp-GalNAc-Ts. These results strongly suggest that variation in both glycan structures and distribution of glycans on the core polypeptides give mucins unique and diverse biological functions that play essential roles in carcinoma-host and other cellular interactions.

Amino Acid Sequence↗
PubMed1999

Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis.

Although Epstein-Barr virus (EBV) has been reported to be present in some 7% of gastric carcinomas, the nature of the background gastric mucosa of carcinoma has not been elucidated. The authors evaluated the degree of gastritis in the background gastric mucosa of EBV-associated gastric carcinoma. EBV was detected using in situ hybridization for EBV-encoded small ribonucleic acid 1 (EBER-1) in carcinoma cells. The authors compared gastritis in surgically resected stomachs with 8 EBER-1-positive and 16 EBER-1-negative gastric carcinomas of a similar histologic type using histologic variables of the Updated Sydney System. All eight lesions of EBER-1-positive gastric carcinomas had intestinal metaplasia in the background. Mild to moderate glandular atrophy was common in both groups. Many of the tested lesions, 87.5% of EBER-1-positive and 62.5% of EBER-1-negative lesions, were located near the mucosal atrophic border. The background gastric mucosa for EBV-associated gastric carcinomas is rich in atrophic changes. EBV-associated gastric carcinomas are located near the mucosal atrophic border.

Gastric Mucosa↗
PubMed1999

An isoenzyme-selective inhibitor of phosphodiesterase 4 and 1, KF19514, may be useful in the treatment of systemic anaphylaxis: an in vivo study in rabbits.

The present study was conducted to determine whether an inhibitor of phosphodiesterases 4 and 1, KF19514, is useful in the treatment of systemic anaphylaxis in fentanyl-anesthetized rabbits. Eighty-two rabbits were randomly allocated to 7 groups. Groups I-1 (0.01 mg x kg(-1)), I-2 (0.1 mg x kg(-1)), and I-3 (1 mg x kg(-1)) received KF19514 10 minutes before antigen challenge, with Group II serving as control. Group IV and Group V received KF19514 and aminophylline 1 minutes after antigen challenge, respectively, with Group III serving as control. The survival rate was higher in Groups I than in Group II, rates were similar in Groups I-1, I-2, and I-3. The survival rate was also higher in Group IV than in Group III. Pulmonary resistance (R(L)) was significantly lower in Groups I-2 and I-3 than in Group II. Dynamic pulmonary compliance (C(dyn)) was significantly higher in Group I-3 than in Group II. Heart rate and central venous pressure were similar in Groups I and II. In Groups III, IV, and V, heart rate and mean arterial pressure were comparable, but central venous pressure in Group IV was significantly lower than in Group V. In conclusion, the administration of KF19514, an inhibitor of PDEs 4 and 1, to rabbits either before or after antigen challenge improved bronchoconstriction provoked by systemic anaphylaxis with minimal concomitant cardiovascular side effects compared with aminophylline, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Inhibition of human immunodeficiency virus type 1 replication in acutely and chronically infected cells by EM2487, a novel substance produced by a Streptomyces species.

In a search for effective HIV-1 transcription inhibitors, we have evaluated more than 75,000 compounds for their inhibitory effects on Tat-induced human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-driven reporter gene expression and found that EM2487, a novel small-molecule substance produced by a Streptomyces species, is a potent and selective inhibitor of HIV-1 replication in both acutely and chronically infected cells. Its 50% effective concentration for acute HIV-1 infection was 0.27 microM in peripheral blood mononuclear cells (PBMCs), while the 50% cytotoxic concentration for mock-infected PBMCs was 13.3 microM. EM2487 proved inhibitory to a variety of HIV-1 strains and HIV-2 in acutely infected T-cell lines (MOLT-4 and MT-4). The compound could suppress tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 production in latently infected cells (OM-10.1 and ACH-2) as well as constitutive viral production in chronically infected cells (MOLT-4/III(B) and U937/III(B)) without showing any cytotoxicity. EM2487 did not affect early events of the HIV-1 replication cycle, as determined by proviral DNA synthesis in acutely infected MOLT-4 cells. In contrast, the compound selectively prevented viral mRNA synthesis in OM-10.1 cells, suggesting that HIV-1 inhibition occurs at the transcriptional level. Furthermore, EM2487 did not inhibit TNF-alpha-induced HIV-1 LTR-driven reporter gene expression but did inhibit that induced by Tat, irrespective of the presence or absence of the nuclear factor kappaB binding sites in the LTR. These results suggest that the mechanism of action is attributable in part to the inhibition of Tat function.

Anti-HIV Agents↗
PubMed1999

Trousseau's syndrome with brachiocephalic vein thrombosis in a patient with uterine carcinosarcoma. A case report.

The authors treated a patient with the previously unreported occurrence of brachiocephalic vein and superior vena cava thrombosis in association with a distantly located cancer. A 71-year-old woman presented with swelling over the right side of the neck and abdominal distension. Physical examination revealed a huge mass, and computed tomography demonstrated thrombosis of the brachiocephalic vein and superior vena cava accompanied by jugular vein dilatation. No coagulation disorder was demonstrable. After anticoagulation and thrombolysis, hysterectomy was performed; microscopic examination of the specimen revealed uterine carcinosarcoma. Even though local tumor obstruction is a much more common cause of neck vein thrombosis, a distant occult cancer can present as this form of Trousseau's syndrome. In patients with otherwise unexplained neck vein thrombosis, examination not only of the head and neck but also of the abdomen and pelvis should be pursued.

Aged↗
PubMed1999

Glycyrrhizin inhibits TNF-induced, but not Fas-mediated, apoptosis in the human hepatoblastoma line HepG2.

To determine the transaminase-lowering action of glycyrrhizin (GL) immunologically, the effect of GL on tumor necrosis factor (TNF)-alpha- and Fas-mediated apoptosis was assessed using a human hepatoblastoma line, HepG2 cells. The HepG2 cells were resistant to TNF-alpha and anti-Fas antibody, but were rendered susceptible to TNF-alpha and anti-Fas antibody in the presence of actinomycin D (Act D), an inhibitor of RNA synthesis. The cytotoxicity induced by TNF-alpha/Act D or anti-Fas/Act D was accompanied by DNA fragmentation, indicating apoptotic death of HepG2 cells. GL partially prevented the apoptosis of HepG2 cells induced by TNF-alpha/Act D in a GL-dose dependent fashion. However, this protective effect of GL was not observed in the cytotoxicity of HepG2 caused by anti-Fas/Act D. Although the protection mechanism of GL, observed in a limited fashion against TNF-alpha-mediated apoptosis, is unclear, the present results provide an immunological explanation for the transaminase-lowering action of GL in the GL treatment of chronic liver diseases involving apoptotic hepatocyte death in their pathogenesis.

Anti-Infective Agents↗
PubMed1999

Mixed base of hydrophilic ointment and purified lanolin to improve the drug release rate and absorption of water of minocycline hydrochloride ointment for treatment of bedsores.

A desired ointment bases for better treatment of bedsores was developed to improve the release rate of minocycline hydrochloride (MH) and the water absorption capacity using various types of hydrophobic to hydrophilic ointment base. The influence of purified lanolin (PL) on the release behavior of MH from hydrophilic ointment (HO) base was primarily focused on. It was found that the release rate of drug increased with increase in the hydrophilicity of the base. A linear correlation between the apparent release rate constant of drug from the HO and PL mixed ointment base at various combination ratios and the elution of ointment base was noted. The HO ointment base containing 30% PL had the highest apparent release rate constant of MH. The mixed ointment base with the lowest viscosity showed the highest absorption of water and elution of ointment base. In conclusion, it was found that HO (70%) and PL (30%) mixed ointment base was a promising candidate for better treatment of bedsores.

Anti-Bacterial Agents↗
PubMed1999

Retrolabyrinthine presigmoid transpetrosal approach for selective subtemporal amygdalohippocampectomy.

The retrolabyrinthine presigmoid transpetrosal approach is a modification of the subtemporal approach which is suitable for complete amygdalectomy. By drilling away the retrolabyrinthine presigmoid petrosal bone, at least 1 cm more space below and 1 cm more space medially is obtained than in the subtemporal approach, and temporal retraction pressure is diminished when approaching from below. Operative results according to the Engel's classification of seizure control, and pre- and postoperative Wechsler Adult Intelligence Scale (WAIS), revised WAIS, and Wechsler Intelligence Scale for Children scores were measured in 16 patients treated by normal or modified subtemporal amygdalohippocampectomy. Postoperative follow-up ranged from 8 to 79 months. There has been no morbidity or mortality among these 16 patients, and postoperative seizure frequency has been diminished to less than 10% of the preoperative level in 15 of the 16. In eight patients, seizures have been eliminated totally. Subtemporal amygdalohippocampectomy achieved significantly increased performance and full scale intelligence quotient within 2 months after surgery, compared to preoperative levels. Subtemporal amygdalohippocampectomy is an alternative to the transsylvian approach, but is less invasive.

Adult↗
PubMed1999

Regulation of plasma and liver total cholesterol levels by dietary oleic acid in rats fed a high-cholesterol diet.

The effects of diets containing fats and oils or fatty acids on the lipid metabolism were investigated in male rats of the Wistar strain fed hypercholesterolemic diets, especially focusing our attention on the correlation between dietary oleic acid (OLE) contents and the levels of plasma and liver total cholesterol (T-CHOL) or the fatty acid profiles in plasma and liver CHOL-ester. In the rats fed the free (FR)-type fatty acids, the concentrations of plasma and liver T-CHOL were high and the amounts of neutral steroids excreted into the feces were low when compared with those of rats given the triacylglycerol (TG)-type fatty acids, showing that TG-type fatty acids suppress the intestinal CHOL absorption more than the FR-type fatty acids do. The concentrations of plasma T-CHOL were highest in rats fed the oleic acid (OLE)-rich diets, followed in order by rats supplied with the palmitic acid (PAL)-rich diets, the hydrogenated coconut oil (HCO) diet, and the linoleic acid (LIN)-rich diets; the lowest was in rats given tristearin (TSTE) and linseed oil (LIS) diets. A positive correlation was obtained between the dietary OLE contents and the levels of plasma and liver T-CHOL or OLE in the plasma and liver CHOL-ester, and an inverse correlation between dietary OLE contents and the amounts of excreted neutral steroids. These results suggest that the dietary OLE contents regulate the levels of plasma and liver T-CHOL in CHOL-loaded rats.

Animals↗
PubMed1999

[Digital rectal examination, transrectal ultrasonography and prostate specific antigen for diagnosis of prostate cancer in clinical urological practice-detection of impalpable cancer].

OBJECTIVE: The clinical usefulness of multimodality detection for prostate cancer by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and serum PSA determination (PSA) was evaluated in this retrospective study. PATIENTS AND METHODS: A total of 1344 symptomatic male patients who underwent DRE, TRUS and PSA in our outpatient clinic were studied. Prostate biopsies were performed when at least one diagnostic test was positive. RESULTS: Of 1344 patients, 436 (32.4%) had positive test results. Among 403 patients who underwent biopsy, 121 patients (30.0%) were found to have prostate cancer. The overall cancer detection rate was 9.0%. Among the 121 cancer patients, if examination had been carried out using only one or two tests, cancer would have not been detected in 22 patients (18.2%) by DRE alone, 27 patients (22.3%) by TRUS alone, 18 patients (14.9%) by PSA alone, 12 patients (9.9%) by a combination of DRE and TRUS, and 6 patients (5.0%) by a combination of DRE and PSA. Among the 121 patients with cancer, 22 (18.2%) had impalpable cancer. Impalpable cancer was more likely to be localized (77.3%) than palpable cancer (28.3%, p < 0.001) and more likely to be well or moderately differentiated (72.7%) than palpable cancer (41.4%, p = 0.008). CONCLUSION: This study confirmed the need for multimodality detection using DRE, TRUS and PSA as complementary methods in order to minimize decrease in cancer detection. In particular, impalbable cancers not detectable by DRE were detected and were revealed to be more likely to be localized and amenable to curative therapy. These results therefore underscore the importance of multimodality detection for early diagnosis of prostate cancer in urological practice.

Adult↗
PubMed1999

[Screening of urogenital malignancies by transabdominal ultrasonography in "human dry dock"].

BACKGROUND: Transabdominal ultrasonography (US) has been widely accepted as a diagnostic method with which to examine multiple organs simultaneously. This study was designed to evaluate the efficacy of trans-abdominal US to screen for urogenital malignancies. METHODS: From 1993 through 1997 109,077 men and 28,023 women underwent abdominal US to screen for abdominal and pelvic diseases as part of a regular health check-up program at the Tokyu Medical Health Center. RESULTS: Twelve renal cell cancers (RCCs), 7 bladder tumors (BTs), 4 prostatic cancers (PCs), and 1 testicular tumor (TT) were detected. All cancers were diagnosed pathologically and treated surgically except for one PC. Surgical pathological examination and conventional imaging revealed that all 12 RCCa and 6 of the 7 BTs were of less advanced stage than pT1N0M0. However, all 3 PCs and the TT were pT3N0-1M0 and pT1N3M0, respectively. The stage and grade of these 12 RCCs were significantly lower than those of 29 symptomatic RCCs. All 12 patients with RCC patients and 6 of the 7 patients with BT had no urological symptom, whereas 3 of the 4 patients with PC and the patient with TT had urogenital symptoms. Microscopic examination of the urine revealed both red blood cells and tumors cells in two of the seven patients with BT. All four patients with PC had serum levels of prostatic-specific antigen greater than 4 ng/ml. CONCLUSION: These results indicate that screening by transabdominal US as part of regular health check-ups can detect many types of urogenital malignancy. In particular, US is useful for detecting low-grade and low-stage RCCs and superficial BTs but is less sensitive for early-stage PCs and TTs.

Adult↗
PubMed1999

EM2487, a novel anti-HIV-1 antibiotic, produced by Streptomyces sp. Mer-2487: taxonomy, fermentation, biological properties, isolation and structure elucidation.

For the purpose of discovering novel agents that inhibit HIV-1 replication at the transcriptional level, we have established cell lines reflecting the HIV-1 long terminal repeat-driven gene expression. Using these cell lines, we have screened approximately 10,000 microorganism products and found that the culture supernatant of Streptomyces sp. Mer-2487 suppresses the HIV-1 Tat-induced gene expression without affecting the basal or tumor necrosis factor-alpha-induced transcription. The purified active component has a unique structure, as shown in Fig. 1. This compound has an inhibitory effect on HIV-1 replication in chronically infected cells as well as acutely infected cells, suggesting that the inhibition occurs at a postintegration step of HIV-1 proviral DNA in the HIV-1 replication cycle.

Anti-Bacterial Agents↗
PubMed1999

[A case of noninflammatory corneal edema following anterior-posterior radial keratotomy successfully treated by topical steroids].

BACKGROUND: Corticosteroids seems to affect the functions of corneal endothelial cells directly in addition to its anti-inflammatory effect. CASE: A 69-year-old male presented with left blurred vision and decreased visual acuity in both eyes. He had undergone anterior-posterior radial keratotomy for myopia in both eyes 40 years before. Both eyes showed mild corneal stromal edema in the pupil area. We diagnosed the condition as corneal edema secondary to cell loss and dysfunction of corneal endothelium after surgery. The stromal edema further advanced in the left eye one month later. The corneal thickness increased from the initial value of 619 to 631 microns. The corrected visual acuity decreased from 0.5 to 0.06. There were no signs suggesting inflammatory reaction. The left eye was then treated with topical corticosteroids as eye-drops and by subconjunctival injection. The corneal thickness decreased to 546 microns two months later with improvement of visual acuity to 0.5. CONCLUSION: This case illustrates that topical corticosteroids may be effective for corneal edema through their anti-inflammatory effect and possible activation of the endothelium.

Administration, Topical↗
PubMed1999

[Retroperitoneal schwannoma: a case report].

A 67-year-old man was admitted for a complaint of lumbago. The patient had had the three operations for the schwannoma in spinal cord at the Neurosurgical Department of our hospital. Magnetic resonance imaging (MRI) revealed a right infrarenal tumor by chance. The tumor compressed the right kidney and measured 6 x 5 cm in size. On the tentative diagnosis of the retroperitoneal tumor, the patient was referred to the department of urology in our hospital and the tumor was excised. The histological diagnosis of the removed retroperitoneal tumor was schwannoma, and was thought to be heterotopic recurrent schwannoma.

Aged↗
PubMed1999

Intrinsic inhibitor of inositol 1,4,5-trisphosphate binding.

Rat brain cytosol was applied to a heparin column and eluted with 0.9 M-NaCl. The total binding activity of [3H]inositol 1,4,5-trisphosphate to the eluate was increased about 6-fold compared with the original cytosol. When the eluate was mixed with a flow-through fraction from the heparin column, however, the activity returned to the original level, suggesting that the flow-through fraction contained an inhibitory factor(s) which prevented the binding. The factor(s) was purified by sequential column chromatography using gel permeation, a hydrophobic gel, and finally, a hydroxylapatite gel. Silver staining of sodium dedecyl sulfate gel electrophoresis of the sample thus purified showed a broad band located between the authentic molecular weight markers of 580 and 390 k. A carbohydrate staining method showed that the factor is a glycoprotein.

Animals↗