Rational design and synthesis of a novel class of active site-targeted HIV protease inhibitors containing a hydroxymethylcarbonyl isostere. Use of phenylnorstatine or allophenylnorstatine as a transition-state mimic.

A novel class of HIV-1 protease inhibitors containing a hydroxymethylcarbonyl (HMC) isostere were designed from the substrate transition state and synthesized. Phenylnorstatine [Pns; (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] and the 2S diastereomer, (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid, named allophenylnorstatine (Apns) were effective transition-state mimics, and incorporation of Pns-Pro or Apns-Pro at the P1-P1' site gave potent and specific HIV-1 protease inhibitors. In the inhibitory assays, the chemically synthesized [Ala67,95] HIV-1 protease was used.

Improvement of gelatin particle agglutination test for detection of anti-HTLV-I antibody.

Partial modifications of antigen components were made to improve the gelatin particle agglutination (PA) test for the detection of antibodies against human T cell leukemia virus type-I. Envelope glycoproteins prepared by lentil lectin affinity chromatography were further added to the purified viral antigens to be coated on the gelatin particles. Comparative studies with a conventional PA test kit (Serodia ATLA) and indirect immunofluorescence assay showed that the specificity and sensitivity of the new PA test were increased and that abnormal agglutination such as the prozone phenomenon was abolished by this improvement.

Geographical distribution of subjects seropositive for human T-cell leukemia virus type 1 in Papua New Guinea.

Of 1471 sera collected from 1986 to 1989 in Papua New Guinea (PNG), 2.2% were found to be positive for anti-HTLV-1 antibody by successive particle agglutination and immunofluorescence tests. The seropositive rate varied in different provinces and was higher in the coastal areas of the main island and in neighboring small islands than in the highlands of PNG.

[The development of a highly sensitive IgE immunoradiometric assay using monoclonal antibodies].

We have developed two-site immunoradiometric assay (IRMA) for quantitation of human serum IgE, using two different anti-IgE monoclonal antibodies which recognize different epitopes on IgE molecule. We obtained 25 different monoclonal antibodies classified seven groups, and then two different monoclonal antibodies were selected for bead coater and tracer after checking the titer and specificity of each antibody. IgE IRMA we developed here showed good performance in terms of specificity, sensitivity and reproducibility.

A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin.

A new potent antibacterial protein, for which we propose the name royalisin, was found in royal jelly of the honeybee Apis mellifera L. and purified to homogeneity for the first time by acid extraction, gel filtration, and reverse-phase high pressure liquid chromatography. The primary structure of royalisin was determined to consist of 51 residues, with three intramolecular disulfide linkages, having a calculated molecular mass of 5523 Da.

Studies on the synthesis of compounds related to adenosine-3',5'-cyclic phosphate. VI. Synthesis and cardiac effects of N6,N6,2'-O-trialkyl-, N6,2'-O-dialkyl-, and 2'-O-alkyladenosine-3',5'-cyclic phosphates.

The alkylation of adenosine-3',5'-cyclic phosphate (cAMP, 1) with alkyl bromides was investigated and various new alkylated cAMP derivatives, N6,N6,2'-O-trialkyl cAMPs (2), N6,2'-O-dialkyl cAMPs (3) and 2'-O-alkyl cAMPs (4), were prepared by a one step reaction without the introduction of a protecting group into 1. Compounds (2) were synthesized from 1 by treatment with alkyl bromides in the presence of NaH or potassium tert-butoxide in dimethyl sulfoxide. Compounds (3) were also synthesized from 1 under conditions similar to those of the synthesis of 2 except for the use of MeONa as a base.

An easy and safe modified method of endoscopic balloon dilation for postgastrectomy anastomotic stricture.

An easy and safe modified method for endoscopic balloon dilation was performed 24 times for 16 patients who had undergone subtotal gastrectomy without any ensuing complications. The balloon dilator was simply attached to the ultraslender forward-viewing fiberscope just above the flexible portion. The balloon dilator can be easily placed into the stricture by advancing the fiberscope into the duodenum under direct vision.

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of surgery].

In a nationwide study conducted in 11 surgical institutions of C-425, a newly developed human native immunoglobulin liquid preparation for intravenous injection, was combined with conventional antibiotic treatment to investigate the efficacy and safety. A total of 47 patients with severe infections which had not symptomatically responded to 3-day or longer treatment with any antibiotics was included. Doctors in charge judged the efficacy of C-425 to be "excellent" in 3 patients, "good" in 13, "fair" in 15, and "poor" in 4.

Performance certification of gelatin particle agglutination assay for anti-HTLV-1 antibody: inconclusive positive results.

In order to test the performance of particle agglutination assay (PA), 800 preselected PA-positive sera at 8 blood centers in the Kyushu area were tested in various assays. Most blood centers should improve their PA technique, since a third of the samples were PA-negative in our hands. A third of our PA high-titer sera were negative in indirect immunofluorescence and enzyme immunoassay, the results of which were consistent with each other.

Patterns of migration indicate sexual transmission of HTLV-I infection in non-pregnant women in Papua New Guinea.

The prevalence of infection with human T-cell leukaemia virus (HTLV-I) was studied in Madang Province on the north coast of Papua New Guinea. Serum specimens collected from non-pregnant women in 17 villages were tested for anti-HTLV-I by gelatin particle agglutination screening and confirmed by immunofluorescence and Western blotting. Overall, 13.

[Immunologic examination of Juzentaiho-to (TJ-48) in postoperative gastric cancer].

Unlabelled: We earlier reported the clinical effects of TJ-48 on side-effects of anti-tumor agents. In this report an immunological examination was conducted on administration of TJ-48 for postoperative gastric cancer.

Materials And Methods: Blast formation of mouse lymphocyte to which patient serum was added.

The first record of a confirmed human case of Gnathostoma doloresi infection.

The first case of Gnathostoma doloresi infection in a human was found in Miyazaki Prefecture, Japan. A whole length of the parasite was dissected out from biopsied skin and was identified as the third-stage larva of G. doloresi based on the morphological characteristics of the hooklets of the head bulb and also on the number of nuclei in the intestinal epithelial cells of the parasite.

Alkylated cAMP derivatives: selective synthesis and biological activities.

Many alkylated cAMPs have been prepared and tested for their antitumor and cardiac activities. Treatment of cAMP with several bases and alkyl bromides gave alkyltriesters of cAMP (2), N6,N6,2'-O-trialkyl cAMPs (3), N6,2'-O-dialkyl cAMPs (4) and 2'-O-monoalkyl cAMPs (5) in one step. N6,N6-dialkyl cAMPs (6) were prepared from 2'-O-tosyl cAMP by the similar alkylation, followed by detosylation.

Impaired natural defence of beige (Chediak-Higashi syndrome) mice against tissue-migrating larvae of Strongyloides ratti and its reconstitution by bone marrow cells.

The susceptibility of C57BL/6-bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak-Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJ/bgJ mice was approximately twice as high as that of their littermate bgJ/+mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ/+mice.

Sporadic carriers of human T-lymphotropic virus type I in northern Egypt.

Sera from 3,158 individuals living in northern Egypt were tested for the presence of antibodies against human T-lymphotropic virus type I (HTLV-I) by the newly developed particle agglutination (PA) test. Ten sera gave a positive reaction in the PA test. Eight of these sera were examined further by Western blotting and all of them gave several bands corresponding to HTLV-I structural proteins.

Immune suppression in healthy carriers of adult T-cell leukemia retrovirus (HTLV-I): impairment of T-cell control of Epstein-Barr virus-infected B-cells.

We have examined the activities of Epstein-Barr virus (EBV)-specific memory T-cells of carriers of adult T-cell leukemia (ATL) associated retrovirus (HTLV-I) and non-carriers in an ATL-endemic area, all of whom were EBV-seropositive, by assay of EBV-induced B-cell focus regression. The result showed that immune suppression, as represented by lowering of the regression, was present in 18 (29%) out of 63 healthy HTLV-I carriers, in contrast to none of 63 matched control persons (healthy non-carriers). This finding suggests that a suppression of cell-mediated immunity is induced by a persistent infection with ATL retrovirus.

Eosinophil response in mast cell-deficient W/WV mice.

The combination of cyclophosphamide treatment and Toxocara canis infection is known as an effective way of causing a high level of eosinophilia in mice. When this treatment was applied to congenitally anemic, mast cell-deficient W/WV mice, eosinophil response was far less than that of their normal littermate +/+ mice. The degree of the defective eosinophil response in the peripheral blood of W/WV mice was severer than that in the bone marrow.

Evaluation of ELISA for the diagnosis of paragonimiasis westermani.

Possible applicability of an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of paragonimiasis westermani was examined using crude extract of adult Paragonimus westermani (Pw) as the test antigen. The mean ELISA values of the sera from Pw egg-positive cases and from clinically suspected cases were more than 22 times higher than that of the healthy control. No, or only marginal, cross-reactivity was observed against Pw antigen using sera from patients with various parasitic diseases other than paragonimiasis, except that from schistosomiasis and clonorchiasis cases.

Seroepidemiology of adult T-cell leukemia virus infection and analysis of sero-positive cases in Taiwan.

For a seroepidemiologic study of adult T-cell leukemia virus (ATLV) infection in Taiwan, the gelatin particle agglutination technique and the indirect immunofluorescence method were used for anti-ATLV titration. Sporadic sero-positive cases were found all over the Taiwan districts except among the aborigines (0/947). Sero-positive rates ranged from 0 to 5.

Activation of 2-5A-dependent RNase by analogs of 2-5A (5'-O-triphosphoryladenylyl(2'----5')adenylyl(2'----5')adenosine ) using 2',5'-tetraadenylate (core)-cellulose.

A variety of 2-5A (px(A2'p)nA; x = 2 or 3, n greater than or equal to 2) analogs were assayed for their abilities to activate murine 2-5A-dependent RNase (subsequently "the nuclease") using a recently developed method. This technique consists of immobilizing and partially purifying the nuclease using core-cellulose [A2'p)3A-cellulose) and then monitoring the breakdown of poly(U)-3'-[32P]Cp into acid-soluble fragments. Several 5'-adenosinecapped analogs of 2-5A (containing a tetra-, tri-, or diphosphate) were analyzed, and it was found that reducing the number of phosphoryl groups between the 5' to 5'-diadenosine linkages resulted in a progressive loss of activity.

Primary infection of Japanese infants with adult T-cell leukaemia-associated retrovirus (ATLV): evidence for viral transmission from mothers to children.

Primary infection with adult T-cell leukemia virus (ATLV) was investigated by follow-up studies on 16 ATLV-seropositive mothers and their breastfed infants in an ATLV-endemic area of Japan. Maternal antibody to ATLV decreased in all the infants, and was detectable in only three of 12 infants tested 6 months after birth. Reappearance of the antibody 9-18 months after birth was observed in only four of the 16 infants.