Biomedical subjects

H Tamamura

Publications and source records attributed to H Tamamura.

At least 55 records · Page 3Linked to original sources

PubMed1995

The synthetic [Tyr5,12,Lys7]-polyphemusin II peptide (T22) binds to the CD4 cell surface molecule.

The [Tyr5,12,Lys7]-polyphemusin II peptide (T22) inhibits HIV-1 replication in lymphocytes. The mechanism of T22 inhibition of HIV-1 replication may involve T22 competition with HIV-1 for attachment sites on the plasma membrane of targeted cells. Here we find that the T22 peptide binds to the CD4 molecule in affinity columns. We also find that antiserum to CD4 inhibits cell attachment to T22. Further CD4+ transfected cells attach to T22 while their parental cells which do not express CD4 do not attach to T22. These data demonstrate that T22 binds to the CD4 molecule and supports the hypothesis that T22 inhibits HIV-1 replication by binding to the cell surface CD4 molecule and inhibiting uptake of the virus.

Amino Acid Sequence↗

PubMed1995

Disulfide bond-forming reaction using a dimethyl sulfoxide/aqueous HCl system and its application to regioselective two disulfide bond formation.

Disulfide bond formation in S-acetamidomethyl (Acm) cysteine-containing peptides by successive treatments with silver trifluoromethanesulfonate (AgOTf) and dimethyl sulfoxide (DMSO)/aqueous HCl is described. An S-Acm cysteine was found to be quantitatively converted into cysteine by deprotection of the Acm group with AgOTf followed by DMSO/aqueous HCl treatment. Under these reaction conditions, no significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr and Trp. Oxytocin and a Trp-containing peptide, urotensin II, were prepared by this method. Furthermore, regioselective two disulfide bond formation was found to be feasible by the combination of air oxidation and the AgOTf-DMSO/HCl system. This strategy has been successfully applied to the syntheses of tachyplesin I and endothelin I, which have two disulfide bonds and a Trp residue in the molecule.

Amino Acid Sequence↗

PubMed1995

A single retroviral gag precursor signal peptide recognized by FBL-3 tumor-specific cytotoxic T lymphocytes.

Several dominant T-cell receptors of cytotoxic T-lymphocyte (CTL) clones specific for FBL-3 tumor antigen were clonally amplified in mixed lymphocyte tumor cell cultures derived from an individual immune mouse. Every CTL clone analyzed had a common specificity for a single epitope in the precursor to cell membrane-associated nonstructural gag-encoded protein, Pr75gag, which can be minimally identified by nine amino acid residues, SIVLCCLCL. This epitope is located within the hydrophobic signal sequence motif that mediates translocation of the protein into the endoplasmic reticulum. These novel observations suggest that expression of Pr75gag in FBL-3 tumor cells led to the amplification of CTLs which recognize the signal sequence of the nonstructural gag-encoded glycoprotein precursor.

Amino Acid Sequence↗

PubMed1995

Solution-phase synthesis of an anti-human immunodeficiency virus peptide, T22 ([Tyr5,12,Lys7]-polyphemusin II), and the modification of Trp by the p-methoxybenzyl group of Cys during trimethylsilyl trifluoromethanesulfonate deprotection.

T22 ([Tyr5,12,Lys7]-polyphemusin II) was previously synthesized by a solid-phase method and was found to have a strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3'-dideoxy-thymidine (AZT). In the present study, the solution-phase synthesis of T22 was attempted in order to produce this peptide on a large scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragments and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf) in trifluoroacetic acid followed by air-oxidation. During this deprotection, a significant by-product derived from the transfer of the p-methoxybenzyl (MBzI) group from the sulfhydryl group of the cysteine residue to the side chain of the tryptophan residue was formed. This side reaction was found to be efficiently suppressed by adopting a two-step deprotection procedure using silver trifluoromethanesulfonate (AgOTf)-TMSOTf or trimethylsilyl bromide (TMSBr)-TMSOTf.

Amino Acid Sequence↗

PubMed1995

Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity.

All disulfide analogs (types I, II and III) of protegrin (PG)-1, an 18-residue antimicrobial peptide having two intramolecular disulfide bonds, were synthesized using regioselective disulfide bond formation. Random air-oxidation of the fully reduced PG-1 formed the type III PG-1. In addition, a type III analog containing an amidated carboxy-terminal residue was also prepared. Each analog showed significant and different antibacterial and anti-human immunodeficiency virus (HIV) activity. Deletion of two disulfide bridges caused a significant decrease in activity.

Amino Acid Sequence↗

PubMed1994

Structure-activity relationships of an anti-HIV peptide, T22.

T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have a strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). We studied the structure-anti-HIV activity relationships of T22 and determined the following information. The number of Arg residues in the N-terminal and C-terminal regions of T22 is closely related with anti-HIV activity. Disulfide rings, especially the major disulfide ring, are indispensable for anti-HIV activity and maintenance of the secondary structure. Between two repeats of Tyr-Arg-Lys, which are a characteristic structure contained in T22, Tyr-Arg-Lys in the N-terminal portion is more closely related with anti-HIV activity. We found some compounds having a higher selectivity index (50% cytotoxic concentration/50% effective concentration) than that of T22.

Amino Acid Sequence↗

PubMed1994

Lymphocytes and promonocytes attach to the synthetic [Tyr5,12, Lys7]- polyphemusin II peptide.

The [Tyr5,12,Lys7]-polyphemusin II peptide (T22) has been shown to inhibit HIV-1 replication in lymphocytes. The mechanism of T22 inhibition of HIV-1 replication is not known but may involve T22 competition with HIV-1 for attachment sites on the plasma membrane of targeted cells. Here we find that three human immunocyte cell lines (H9, Jurkat, and U-937) attach to T22. The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), has been shown to activate intracellular protein kinase C and to stimulate lymphocyte attachment to various substrates through specific cell surface receptors. Here we find that TPA treatment enhances attachment of the immunocytes to T22 by three- to four-fold. These data demonstrate that T22 binds to immunocyte cell surfaces and support the hypothesis that T22 may inhibit HIV-1 replication by competing with the virus for a common cell surface receptor(s).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Fine structure of a virus-encoded helper T-cell epitope expressed on FBL-3 tumor cells.

Antigen peptide fn20 representing Friend murine leukemia virus env122-141 (DEPLTSLTPRCNTAWNRLKL) is recognized by two independent Friend virus-induced, FBL-3 tumor-specific helper T-cell (Th) clones. We isolated more Th clones from mice immunized with fn20 peptide. We examined the fine structure of the peptide required to activate a large group of fn20-specific Th clones. A systematic analysis of peptides of decreasing lengths eliciting Th proliferation defined the minimum core length as 13 amino acids (LTSLTPRCNTAWN). Functional proliferation and competition assays with variant peptides with alanine substitutions permitted the assignment of five peptide residues in two major histocompatibility complex-interacting and three T-cell-receptor-interacting sites. Th clones were different in their reactivities toward peptides of various lengths and the variant peptides.

Amino Acid Sequence↗

PubMed1994

Molecular parameters for the anti-human immunodeficiency virus activity of T22 ([Tyr5,12, Lys7]-polyphemusin II).

T22 ([Tyr5,12, Lys7]-polyphemusin II) was found to exhibit strong anti-human immunodeficiency virus (HIV) activity and exert its effects on a virus-cell fusion process. In the present study, the all-D enantiomer of T22 and its related compounds were synthesized to examine the molecular parameters required for the interaction of T22 with membrane components of cells or viruses in order to exert this anti-HIV activity. The anti-HIV activity of these analogs was investigated in comparison with their membrane permeability with aspect to large unilamellar vesicles (LUVs). The all-D enantiomer of T22 exhibited a 20-fold lower anti-HIV activity compared with T22, whereas they both showed the same membrane permeability. No positive correlation between anti-HIV activity and membrane permeability was observed. These results suggest that the anti-HIV activity of T22 is mediated through the interaction with chiral component(s) of the cell or virus.

Amino Acid Sequence↗

PubMed1994

[Bronchial arterial hemodynamics after thoracic irradiation therapy in lung cancer patients].

We evaluated bronchial arterial hemodynamics after thoracic irradiation therapy. We performed bronchial arteriography in 9 patients (8 males and 1 female) with lung cancer who received thoracic irradiation (58-72 Gy). Three patients had adenocarcinoma, 3 squamous cell carcinoma, 2 small cell carcinoma and 1 large cell carcinoma. Their clinical stages were 6 in stage IIIB and 3 in stage IV. Eight of these cases also received chemotherapy by intra-bronchial arterial infusion of anti-cancer agents (Carboplatin and/or Cisplatin). The bronchial arterial supply was patent except in the one complete remission case (small cell carcinoma of stage IIIB). In the five cases developing radiation pneumonitis, bronchial arteries demonstrated angiogenesis in the radiation fields, despite which pulmonary arteriography and/or pulmonary perfusion scintigrams showed a decreased pulmonary arterial supply. Bronchial arterial hemodynamics demonstrated no significant damage in the bronchial arteries by the thoracic irradiation therapy and/or bronchial arterial infusion of anti-cancer agents. It is suggested that patent bronchial arteries after radiation therapy promote local recurrences of lung cancer. In 5 cases, including 2 local relapsed cases and 3 cases showing no remarkable response to radical radiation therapy, we performed bronchial arterial infusion of anti-cancer agents after radiation therapy, with good responses obtained. We conclude that thoracic irradiation did not damage bronchial arteries as compared with pulmonary arteries, and that in local relapsed and radio-resistant cases bronchial arterial infusion of anti-cancer agents after radiation therapy is a useful approach.

Adult↗

PubMed1994

[A study on the dosage of carboplatin for bronchial arterial infusion in combination with radiation therapy].

Radiation therapy holds an important position as one of the multidisciplinary methods of treating lung cancer (non-small cell carcinoma). As a result of the development of platinum preparations such as cisplatin (CDDP) and wide use of digital subtraction angiography (DSA), selective bronchial arterial infusion (BAI) therapy made possible more effective use of anti-lung cancer drugs. The use of radiation therapy in combination with BAI is now recommended as a more effective method. Meanwhile carboplatin (CBDCA) has recently been developed as a second generation platinum preparation with less side effects, and is being used for BAI, too. However, the maximum tolerated dose (MTD) of CB DCA for BAI to be used in combination with radiation therapy is not known yet. We, therefore, carried out a phase-study to determine MTD of CBD CA for combination with radiation therapy. The results show that the MTD of CBDCA is 400 mg/m2, and that clinically recommendable infusion limit is 350 mg/m2. In an angiographic study performed at the same time, a plural number of tumor affected blood vessels were found in 81.3% of the patients with lung cancer. Therefore, infusion of a drug for such patients should be carefully applied.

Aged↗

PubMed1993

A comparative study of the solution structures of tachyplesin I and a novel anti-HIV synthetic peptide, T22 ([Tyr5,12, Lys7]-polyphemusin II), determined by nuclear magnetic resonance.

The solution structure of tachyplesin I, which was isolated from membrane acid extracts of the hemocytes from the Japanese horseshoe crab (Tachypleus tridentatus), was determined by nuclear magnetic resonance (NMR) and distance geometry calculation. Tachyplesin I takes an antiparallel beta-sheet structure with a type-II beta-turn. Recently, among more than 20 synthetic peptides associated with tachyplesin and its isopeptide (polyphemusin), we found that a novel compound, which we designated as T22 ([Tyr5,12, Lys7]-polyphemusin II), strongly inhibited the human immunodeficiency virus (HIV)-1-induced cytopathic effect and viral antigen expression. The solution structure of T22 was investigated using NMR, and its secondary structure was confirmed to be similar to that of tachyplesin I. The anti-parallel beta-sheet structure and the several amino-acid side chains on the plane of the beta-sheet of T22 are thought to be associated with the expression of anti-HIV activity.

Amino Acid Sequence↗

PubMed1993

Acceleration of the N alpha-deprotection rate by the addition of m-cresol to diluted methanesulfonic acid and its application to the Z(OMe)-based solid-phase syntheses of human pancreastatin-29 and magainin 1.

In solid-phase peptide synthesis, the addition of m-cresol to diluted methanesulfonic acid (MSA) in dichloromethane accelerated the deprotection rate of the acid-labile alpha-amino protecting group, the p-methoxybenzyloxycarbonyl (Z(OMe)) group. Further, 0.1 M MSA, 20% m-cresol/CH2Cl2 was found to be a practically useful N alpha-deprotecting reagent system, since the deprotection of the Z(OMe) group occurred selectively within 30 min at room temperature, leaving intact the other side chain protecting groups, such as benzyloxycarbonyl, benzyl ester, S-p-methoxybenzyl and NG-mesitylene-2-sulfonyl groups. This reagent system was applied to the Z(OMe)-based solid phase syntheses of human pancreastatin-29 and magainin 1.

Amino Acid Sequence↗

PubMed1993

Antimicrobial activity and conformation of tachyplesin I and its analogs.

We investigated the structure-antimicrobial activity relationship of tachyplesin I (T-I). Even when Lys1 and Trp2 were both deleted from the N-terminal end of T-I, the antimicrobial activity against gram-negative bacteria was not decreased. But as Lys1 and Trp2 were deleted one by one, the antimicrobial activity against gram-positive bacteria and antiviral activity were gradually decreased. Deletion of two disulfide bridges caused a significant decrease in all activities. The circular dichroism (CD) spectra revealed that the analogs containing the two disulfide bridges took a beta-sheet structure and that the analogs without the disulfide bridges took a random coil conformation. These results suggest that the beta-sheet structure maintained by two disulfide bridges plays an important role in the antimicrobial activity of T-I.

Amino Acid Sequence↗

PubMed1993

[A case of radiation pneumonitis caused by treatment of lung cancer which revealed marked hypervasculality on bronchial arteriography].

A 44-year-old man was admitted to our hospital because of hemoptysis. He had been admitted to our ward in June 1991, after resection of a brain tumor at another hospital due to cerebral metastasis of lung cancer (adenocarcinoma). Systemic chemotherapy and pulmonary irradiation therapy were performed during the first hospitalization. Radiation pneumonitis occurred 1 month after the completion of radiotherapy, which responded to administration of corticosteroids. One year and 4 months later after the completion of radiotherapy, he was readmitted to our hospital because of hemoptysis. Chest computed tomogram and bronchoscopy showed no recurrence of lung cancer, so pulmonary arteriography and bronchial arteriography were performed to investigate the cause of hemoptysis. Pulmonary arteriograms showed diminished vascularity in the area of radiation fibrosis, but a bronchial arteriogram showed inflammatory hypervascularization in the same field. We considered that the bronchial arterial angiogenesis induced by radiation pneumonitis was the cause of hemoptysis. Bronchial arteriography is necessary in cases of radiation pulmonary fibrosis with hemoptysis without obvious recurrence of tumor. If the growth of new blood vessels in the bronchial artery can be induced by radiation therapy, the administration of anti-cancer agents to the bronchial artery should be considered in the treatment of recurrent lung cancer after radiation therapy.

Adenocarcinoma↗

PubMed1993

[Percutaneous removal of foreign bodies from the cardiovascular system: two experienced cases in addition to a review of 35 cases reported over the past 9 years in Japan].

From 1984 to 1992 in Japan, 37 cases, including 2 cases of our own, have been reported to involve the percutaneous removal of foreign bodies from the cardiovascular system by catheter. We reviewed the cases of these foreign bodies and the locations, approaches and types of catheters used for removal. The reported foreign bodies were usually iatrogenic in origin and were approximately two times larger than those found in patients who had self-dislodged catheters. The most common catheter approaches were from either the right femoral or saphenous veins.

Aged↗

PubMed1992

A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II).

Tachyplesin and polyphemusin are antimicrobial peptides recently isolated from the hemocytes of horseshoe crabs (Tachypleus tridentatus and Limulus polyphemus). We synthesized them and their analogs and examined their antiviral activity against human immunodeficiency virus (HIV) type 1 in vitro. The infection of human T cells with the virus was markedly inhibited by some of them at low concentrations. In this structure-activity study, we found that [Tyr5,12, Lys7]-polyphemusin II, which was designated as T22, had extremely high anti-HIV activity. Its 50% inhibitory concentration (EC50) was 0.008 micrograms/ml, while its 50% cytotoxic concentration (CC50) was 54 micrograms/ml and these values were comparable to those of AZT. This result indicates that T22 would be a potential candidate for the therapy of HIV infection.

Amino Acid Sequence↗

PubMed1991

Orbital fractures: surface coil MR imaging.

Twenty-six patients with orbital fractures diagnosed with plain radiography and computed tomography were examined with surface coil magnetic resonance (MR) imaging. Fifteen patients had blow-out fractures, and 11 had maxillofacial complex fractures. In all patients with blow-out fractures, the location of the fracture was precisely indicated by the presence of prolapsed orbital fat. Incarceration of the extraocular muscle or orbital fat was correctly diagnosed with MR imaging, which was less sensitive in depicting maxillofacial fractures but was useful in assessment of soft-tissue involvement. Postoperative follow-up MR studies provided valuable information about the cause of motility impairment. While T1-weighted images are useful for the detection of the fracture site, both T1- and T2-weighted images are usually necessary for evaluating soft-tissue lesions. The results of this study indicate that surface coil MR imaging is an important adjunct procedure in the diagnosis and treatment of orbital fractures.

Adolescent↗