Search

Serologic screening for antibodies to the acquired immunodeficiency syndrome (AIDS) virus human immunodeficiency virus (HIV) has been carried out in Ghana since 1986 when the 1st AIDS case was detected. In general surveys have indicated a low HIV-1 seroprevalence rate among the general population. Of 1852 blood donors screened in 1986 only 2 (0.1%) were positive. None of 168 laboratory workers screened at the same time was seropositive. Also demonstrated has been a relatively low (2.1%) seroprevalence rate among local prostitutes in Accra. However of 151 Ghanaian women who worked as prostitutes in the Ivory Coast 49% were HIV-1 seropositive upon their return to Ghana. Similarly 215 males and females from the general population who had spent time living in the Ivory Coast and other West African countries such as Burkina Faso were found to be seropositive. In all 212 Ghanians have been tested as seropositive for HIV infection in the March 1986-July 1987 period. The greatest number of cases have been reported from Ghanas Eastern Region Greater Accra and Ashanti. The male to female ratio of HIV-positive cases was 1 to 11.6 in 1986 and 1 to 6.3 in 1987. The predominant presenting complaints of AIDS patients in Ghana are weight loss (89%) persistent or intermittent diarrhea (78%) respiratory symptoms (67%) fever and night sweats (56%) and central nervous system symptoms (50%). It is believed that more than 50% of prostitutes in the Ivory Coast are from Ghana. Many of these women return to their home country for holidays or to seek medical care when they develop symptoms of HIV infection. Unless effective intervention is implemented to limit the heterosexual spread of AIDS in Ghana its incidence may soon become as high as it is in Central Africa.

Studies were made on the cellular immunity of 13 African green monkeys (Cercopithecus aethiops) naturally infected with Simian T cell leukemia virus type 1 (STLV-1), closely related to human T cell leukemia virus type 1. They were classified into 3 groups: 1) progressed carrier, 2) carrier, and 3) normal control. This grouping was made according to their hematologic features, i.e., number of peripheral white blood cells, existence of blastoid cells, presence of STLV-1 Ag on PBL and anti-STLV-1 antibody titers. None of the STLV-1 carriers showed any clinical signs, but STLV-1-specific killer T cells was detected in these PBL without in vitro stimulation. In vitro studies on Ag stimulation showed that the STLV-1-specific killer T cells had been fully activated in vivo, and that no augmentation of in vitro stimulation with STLV-1 Ag was necessary, and that primary in vitro stimulation of normal control PBL was not sufficient to induce specific killer T cells. In addition NK cell activity in PBL of infected monkeys were significantly higher than those in the uninfected.

The interpretation of dual seroreactivity with human immunodeficiency virus type 1 (HIV-1) and HIV-2 in blood samples is a serious problem facing AIDS researchers worldwide. Some samples of sera from HIV-1-infected patients showed a serological cross-reaction with HIV-2, causing confusion regarding the serodiagnosis. Therefore, we tried to differentiate these serum samples from those containing real mixed infections with both types of virus. Sera from patients with HIV-1 infections with HIV-2 cross-reacting antibody in Japan were distinguished from sera from patients with mixed infections with HIV-1 and HIV-2 in West Africa by our serological cross-absorption test, which proved to be highly specific and useful for serodiagnosis.

To report the cross-sectional structure of the retina and choroid in eyes with adult-onset vitelliform macular dystrophy as obtained by optical coherence tomography (OCT).Seven patients with adult-onset vitelliform macular dystrophy and one patient with Best disease were examined by fundoscopy, fluorescein and indocyanine green angiography and OCT. Three patients underwent also electro-oculography.1. Seven cases with adult-onset vitelliform macular dystrophy showed a well-circumscribed elevation of a highly reflective band, corresponding to the retinal pigment epithelium 2. In these 7 patients, the space below this band was inhomogeneous and moderately reflective. 3. Four cases out of 7 had a well defined posterior boundary. 4. The patient with Best disease disclosed a different aspect on OCT, although the contour of the lesion was similar to the others.Optical coherence tomography disclosed the structure of the vitelliform lesion in vivo and could be helpful for its pathological interpretation.

UTMS'21 has an infrared beacon as the key infrastructure and is designed to provide drivers with traffic information through two-way communication between individual vehicles and to realize a safe, comfortable and environment friendly traffic society. The system consists of some subsystems, and one of them is a DSSS, which coordinates the traffic control infrastructure advancing function and the car intellectualizing function to improve safety in car traffic and to reduce accidents. The dangerous zone avoidance control system was considered to be most effective to avoid head-on collisions and rear-end collisions among these systems under examination and was selected as the field trial system for introduction.

We investigated apoptosis induced by in vitro infection with the chimeric virus of simian immunodeficiency virus and human immunodeficiency virus (SHIV). Macaque and human peripheral blood mononuclear cells (PBMCs) were infected with pathogenic SHIV-89.6p (89.6p) or nonpathogenic SHIV-NM-3rN (NM-3rN). In macaque PBMCs, the extent of virus production and apoptosis induction in CD4(+) cells was much greater in 89.6p infection than in NM-3rN infection. The result was consistent with our previous study of in vivo SHIV infection. In human PBMCs, 89.6p replicated and induced apoptosis more extensively than did NM-3rN, when the cells were infected with the same infectious doses of the viruses. However, in cells infected with a high dose of NM-3rN, the levels of virus production and apoptosis induction were comparable to those in 89.6p infection. There was no significant difference in the extent of apoptosis induction between 89.6p and NM-3rN infection when growth curves of the two viruses matched. Thus, apoptosis induction by SHIV might depend quantitatively on the amount of virus production rather than on the strains of the virus. Moreover, the correlation between the extent of apoptosis induction and virus pathogenicity in macaque PBMCs has also been found in SHIV-infected macaques. This suggests that the profiles of SHIV infection in vitro reflect the in vivo phenomena. Therefore, the in vitro evaluation of apoptosis induction by SHIV could be useful as a safety test for the development of live-attenuated vaccines.

The switch from a Th1- to a Th2-type cytokine response is reported to be involved in human immunodeficiency virus (HIV) disease progression. To study the effect of IL-6, one of the Th2-type cytokines, on AIDS pathogenesis, we constructed an SIV/HIV-1 chimeric virus (SHIV) having the human IL-6 gene (SHIV-IL6) SHIV-IL6 could replicate in M8166, a human T cell line, as well as in monkey and human peripheral blood mononuclear cells (PBMCs). Along with the SHIV-IL6 replication, IL-6 was detected in the culture supernatant by ELISA. The maximum level of IL-6 was 35, 15, and 8 ng/ml in M8166, human PBMCs, and monkey PBMCs, respectively. The expressed IL-6 was biologically active as shown by the proliferation of IL-6-dependent murine hybridoma (MH-60) cells. The inserted IL-6 gene was stable for at least four passages (45 days after the initial infection) in M8166 cells, suggesting the ability to achieve stable expression of IL-6 in long-term experiments. Therefore, we successfully established an SHIV system expressing IL-6, and this is the first report of an SHIV expressing a Th2-type cytokine. With this system, IL-6 should be expressed in the regions where the virus replicates, and therefore the inoculation of macaque monkeys with SHIV-IL6 is expected to provide further information on the etiology of AIDS.

Chimeric simian and human immunodeficiency viruses (SHIVs) are useful for evaluating vaccine candidates against HIV-1 and for investigating the pathogenesis of HIV-1 in vivo. In addition, SHIVs are candidates for a vaccine against HIV-1 because attenuated SHIVs can induce long-lasting anti-HIV-1 Env humoral and cell-mediated immunity in monkeys without AIDS-like diseases. In this study, we inserted IL-12 genes in a nef-deleted SHIV to increase the ability of the SHIV to induce cell-mediated immunity against HIV-1. The SHIV vector was constructed by deleting the nef gene and replacing it with restriction enzyme sites. Since IL-12 consists of two subunit genes, p35 and p40, SHIVs with one or both of these genes were constructed. SHIVs with either one of the subunit genes could replicate without a deletion of the inserted gene, but SHIVs with two subunit genes replicated poorly and the inserted genes were rapidly deleted. Production of IL-12 was detected when both of the single-subunit SHIVs were coinfected. The production of IL-12 by the coinfection reached 800 pg/ml, and IL-12 was detected after serial passage in cell cultures, although this amount of IL-12 heterodimer was 150-1500 times less than that of the p40 subunits. These IL-12-producing SHIVs are candidates for a live-attenuated vaccine to induce effective cellular immunity against HIV-1.

To better understand the origin of human T-cell leukemia virus type l (HTLV-l) in South America, we conducted a phylogenetic study on 27 new HTLV-ls in Brazil. These were obtained from Brazilians of various ethnic origins, such as Japanese immigrants, whites, blacks and mulattos. We amplified and sequenced proviral DNAs of a part of the long terminal repeats. Phylogenetic trees revealed that all but 6 of the new isolates were not only similar to each other but also similar to HTLV-ls of other South American countries, including those from Amerindians. However, the isolates differed from the HTLV-ls of Africa and Japan. The other six isolates were from Japanese immigrants and were phylogenetically almost identical to HTLV-ls in Japan but different from the majority of South American HTLV-ls, including the other new Brazilian HTLV-ls. These findings indicate that the recent introduction of HTLV-1 from Japan is limited to Japanese immigrants. In addition, the results do not support the prevailing hypothesis that HTLV-ls in South America were introduced by blacks who were brought from Africa as slaves. Rather, these results suggest that the majority of HTLV-1s prevailing in South America have spread from Amerindians, some of whom are likely to have possessed this human retrovirus from the beginning of their settlement in South America.

A 5-year-old boy had an intracerebral hematoma evacuated from the left parieto-occipital region at a local hospital. There was a difficulty in hemostasis during the operation. Postoperatively his neurological state gradually deteriorated. CT scans showed a gradual increase in intracerebral hemorrhage at the operated site. He was transferred to our clinic for further treatment. The preoperative blood coagulation profile showed that the activity of factor XIII was only 4%. The hematoma was removed without any trouble under administration of factor XIII. Postoperative course was also uneventful although the plasma level of factor XIII did not go up higher than 26% in spite of its daily administration. Although factor XIII administration was terminated one month after cranioplasty, the patient showed good recovery and the level of factor XIII spontaneously normalized in 6 months. The cause of the extremely low level of factor XIII in this case is not known, but it could be ascribed to massive hemorrhage.

To understand the origin and past dissemination of human T-cell leukemia/lymphotropic virus type I (HTLV-I) in Latin America, we conducted a phylogenetic study of five new HTLV-I isolates from Argentina. We sequenced partial fragments of long terminal repeats (LTR) of the new HTLV-Is, and then the sequences were subjected to a phylogenetic analysis for comparison with other HTLV-Is of various geographical origins. Our results indicated that all the isolates were members of the Cosmopolitan group. Furthermore, most (four out of five isolates) of the new HTLV-Is belonged to the Transcontinental (A) subgroup, the most widespread subgroup of the four subgroups in the Cosmopolitan group. In this subgroup, they were closely related to HTLV-Is found in other South American countries including those of Amerindians, and were different from those found in Africa. In contrast, the remaining one HTLV-I (ARGMF) did not show any clear similarity to known HTLV-I isolates belonging to the Cosmopolitan group. The close similarity of South American HTLV-Is strongly suggests a common origin of the virus in this continent. Our results do not support the proposed idea of recent introduction of HTLV-I into South America as a consequence of the slave trade from Africa, where phylogenetically different HTLV-Is predominate.

Ninety-four GB virus C/hepatitis G virus (GBV-C/ HGV) RNA-positive serum samples were obtained from all over the world. We found that all 15 GBV-C/HGV isolates from the Pygmies and the Bantu in the Central African region had a 12-amino acid indel (i.e. insertion or deletion) in the non-structural protein (NS) 5A region. Phylogenetic analyses of the NS5A region, using GBV-A as an outgroup, showed that these 15 isolates had diverged from the common ancestor much earlier than the remaining isolates, indicating an African origin of GBV-C/HGV.

In an effort to delineate the origin and evolution of HTLV-I/STLV-I, we have been conducting phylogenetic analyses on LTR sequences of this virus group. HTLV-I isolates newly analyzed in the present study were from Iran, South Africa, Cameroon, Sakhalin and Brazil where little is known concerning the genetic features of HTLV-I. In addition, STLV-I isolates were obtained from non-human primates in Africa and Asia including an isolate from orangutans in Indonesia. Proviral LTR sequences were amplified by nested PCR, and then sequenced. Phylogenetic trees were constructed by the neighbor joining method. The results obtained are: 1) African STLV-I isolates formed one large cluster together with the Central African group of HTLV-I in the tree; 2) Asian STLV-I isolates including that of an orangutan in Indonesia were highly divergent from African STLV-I and the Cosmopolitan group of HTLV-I, but not so closely related to each other and to the Melanesian group of HTLV-I; 3) An HTLV-I isolate of Cameroon Pygmy was related to African STLV-I isolates, but distinct from the Central African group of HTLV-I; 4) The majority of HTLV-I isolates belonged to subgroup A which is the most widespread subgroup of the Cosmopolitan group of HTLV-I, while some Brazilian isolates from descendants of Japanese immigrants belonged to subgroup B which mainly consists of HTLV-I isolates from Japan. 5) In the phylogenetic tree, several HTLV-I isolates of subgroup A from the same areas appear to form monophyletic clusters such as a subcluster of Brazilian and Colombian isolates and that of Iranian isolates.

Eleven human immunodeficiency virus 1 (HIV-1) isolates from Ghanaian acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) patients obtained by our serosurvey in 1986-1994 were genomically analyzed and phylogenetically compared with other known strains. A phylogenetic tree constructed by analyzing the env region indicated that heterogeneous HIV-1 strains were circulating in Ghana and the majority of them (9 of 11 isolates) belonged to clade (subtype) A which is now furiously epidemic in Africa. Another isolate (1 of 11) belonged to clade D, and the remaining one (1 of 11) belonged to "clade G". This "clade G" virus grouped by the env analysis belonged to clade A by its pol sequence, suggesting an A/G intersubtype recombinant. The characteristic sequences in the V3 tip which have not yet been reported were observed in these Ghanaian isolates, which should be taken into account for future vaccine programs.The molecular epidemiology of HIV-1 in Ghana was investigated through genomic and phylogenetic analysis of isolates from 11 AIDS or AIDS-related complex patients obtained in 1986-94. A phylogenetic tree constructed by analyzing the env region indicated that heterogeneous HIV-1 strains are circulating in Ghana. 9 of the isolates belonged to clade A, 1 to subtype D, and 1 to "clade G"--an A/G intersubtype recombinant. The V3 loops of all isolates were composed of 35 amino acid residues--a characteristic not previously described. These molecular data on the genetic variability of the envelope glycoprotein of HIV-1 should be useful for future vaccine studies in West Africa.

BTEB is a GC-box binding transcription factor that can activate human immunodeficiency virus type 1 long terminal repeat and cellular gene promoters containing multiple GC boxes. The present studies showed that although BTEB mRNA was expressed in various tissues of mammals and cell lines, the expression of BTEB protein was confined to the brain and a neuroblastoma Neuro2A (N2A), suggesting that the BTEB expression was translationally regulated in a cell-specific or tissue-specific manner. The BTEB mRNA was characterized by a long (1.26 kilobases( 5'-untranslated region (5'-UTR) containing 10 upstream AUGs (uAUGs) and a GC-rich tract. To examine whether the 5'-UTR controlled the translation in a cell-specific manner, a fusion plasmid composed of the BTEB 5'-UTR and the chloramphenicol acetyltransferase gene was transfected into HeLa and N2A cells. Translational efficiency of the transcribed mRNA was estimated from the chloramphenicol acetyltransferase activity normalized on the basis of the amount of the mRNA. The 5'-UTR was found to decrease the translational efficiency by 7-fold in HeLa cells; that in N2A was not affected. When one of the uAUGs in the 5'-UTR was mutated to AAG, the inhibition of the translation by the 5'-UTR in HeLa cells was reversed; no effect of the mutation was observed in N2A cells. These results suggest that an uAUG in the 5'-UTR of the BTEB mRNA is, at least in part, responsible for the cell-specific translational control of the BTEB expression.

We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay.

Human immunodeficiency virus type 1 (HIV-1) was found as an etiological agent of AIDS in 1983 (as early as 2 years after of the first documentation of the illness). Thereafter, another type, HIV-2, which is also capable of causing AIDS, was isolated in 1986 from West African patients (CLAVEL et al. 1986). Advanced molecular biological techniques promptly enabled us to reveal the way of replication of the viruses and their complete genomic sequences in a very short period. Nowadays, the genomical and structural features of these human exogenous retroviruses are rather well understood, and both HIVs are classified in the lentivirus subfamily.

The first great milestone in the history of synthetic peptides as tools in the biological sciences was achieved at the beginning of 1960’s, when Merrifield published the method of solid phase peptide synthesis (Merrifield, 1963). Although, peptides had been synthetized earlier, the new technology made it possible to synthetize peptides in milligram quantities during few weeks instead of several months. On the other hand the revolution in DNA technology during the decade of 1970 increased dramatically and is increasing continuously the data base of amino acid sequences of biologically important proteins. However, limitations on the systematic use of synthetic peptides to identify all possible sequential epitopes to a given protein sequence remained until the 1980s. Several attempts to rely on guess-work or predictive algorithms to determine, for instance, the loci of antigenic epitopes in viral proteins have been published in the literature (Pfaff et al., 1982; Tainer et al., 1984; Hopp et al., 1986; Thornton et al., 1986). However, the reliability of these predictive algorithms for sequential antigenic epitopes has been shown to be not better than by chance alone (Westhof et al., 1984; Getzoff et al., 1987, 1988). The first and thus far the most effective and practical procedure allowing the systematic synthesis of all possible sequential epitopes is the so called “Multipin Peptide Synthesis System” developed by Geysen et al. (1984). These developments have extensively increased the use of synthetic peptides in the fields of immunology and vaccine research during the last few years.

Aiming to seek the origin and define the prevalence of HTLV-1 infections, 464 blood samples from aboriginal populations proceeding from isolated regions of the north and south of Chile were studied. Antibodies against HTLV were measured with agglutination tests and confirmed with immuno-fluorescence and Western Blotting. Seven out of 107 (6.5%) blood samples from Atacama indians, 2 out of 202 (1%) from Mapuche indians and 3 out of 155 (1.9%) from Huilliche aborigines were positive. These results highlight an important presence of the virus in indigenous populations, specially in the extremes of the country. These findings could suggest an indigenous (mongoloid) origin of HTLV-1 in Chile, specially in Chiloe, where apparently there has been no contact with african or japanese populations, that could be the origin of the contamination.

Feline immunodeficiency virus (FIV) proviral DNA was detected by the polymerase chain reaction method (PCR). PCR products were detected by gel electrophoresis and ethidium bromide staining. The P-10, P-15 and P-24 regions of the gag gene of FIV were chosen as the target sequences for amplification, and three primer pairs were prepared. The PCR products subjected to amplification with each primer pair were found to possess sites of digestion by a restriction enzyme, as hypothesized. They did not react with feline leukemia virus (FeLV)-infected or feline syncytium-forming virus (FeSFV)-infected cell-derived DNA, and specifically amplified FIV-infected cell-derived DNA. FIV proviral DNA was detected by the PCR method with either primer pair (one-step amplification: single PCR) in DNA derived from peripheral blood lymphocytes (PBL) from 7 of 12 FIV antibody-positive cats. When PCR products in each of the 12 cats were subjected to a second amplification using the same primer pair (two-step amplification: double PCR), FIV proviral DNA was detected in all of the cats. When PBL samples collected from three cats that were negative and three that were positive in the single PCR were cultured for a few weeks in the presence of interleukin 2, FIV proviral DNA was detected in all six cats by the single PCR method. The results suggest that either the use of cultured PBL as the sample or the performance of the double PCR method enables simple and specific detection of FIV proviral DNA in PBL.

We report herein a case of chronic actinic dermatitis in which histopathological changes were observed on several occasions during the course of 2 years. The findings were quite different among stages of the eruption. At a half year after the appearance of the lesion, histological findings revealed eczematous changes. However, gradually a granulomatous change appeared with histiocytes and giant cells. Although the mechanism of histogenesis is not clear, the appearance of histiocytic giant cells seems to be unusual in chronic actinic dermatitis.

We constructed ten mutants of simian immunodeficiency virus isolated from African green monkey (SIVAGM), and nine mutants of human immunodeficiency virus type 2 (HIV-2) in vitro. Their infectivity, cytopathogenicity, transactivation potential, virus RNA, and protein synthesis were examined by transfection and infection experiments. Mutations in three structural (gag, pol, env) and two regulator (tat, rev) genes abolished the infectivity of both viruses, but vpx, vpr (HIV-2), and nef were dispensable and mutant viruses were indistinguishable phenotypically from wild type virus. A vif mutant of HIV-2 showed poor infectivity in cell-free condition, whereas SIVAGM mutants grew equally well with wild type virus. In transient transfection assays, rev mutants derived from both viruses produced mainly small mRNA species and no detectable virus proteins and particles. Transactivation potential of tat mutants originated from both viruses was about three- to ten-fold less than that of respective wild type DNAs, generating small amounts of virus.

15113 Background: First-line chemotherapy for advanced/recurrent gastric cancer has limited efficacy, achieving a median survival time (MST) of about 7 months, while addition of second-line and subsequent chemotherapy may prolong MST to about 11.5 months. In practice, however, about half of patients failing with first-line chemotherapy are unable to receive second-line chemotherapy because of worsening of their performance status (PS), disease progression, or toxicities during protracted first-line chemotherapy. We studied the feasibility of a sequential fixed regimen devised to ensure prompt initiation of second-line chemotherapy after first-line failure. Methods: Between December 2002 and December 2006, patients with advanced or recurrent gastric cancer were enrolled who met the following requirements: 1) major organ function preserved; 2) PS 0–2; 3) presence of at least one evaluable lesion; and 4) written informed consent. The treatment regimen consisted of 3 courses of single-agent S-1 or S-1/cisplatin combination followed by weekly paclitaxel (wPTX). The endpoints of the study were entry to the second-line treatment, time to failure (TTF), and MST. Results: Of 39 patients enrolled, 37 completed first- line S-1. Twenty-eight patients (76%) then received wPTX, 2 non-wPTX chemotherapy, and 6 surgery; only 1 received no additional treatments. Second-line wPTX was followed by a third-line treatment in 23/28 patients (82%). The TTF with the sequential fixed regimen was 7 months. The MST and the 1- and 2-year survival rates in the 37 completing first-line treatment were 14.6 months, 61% and 25%, while those in the 28 switched over to wPTX were 12.5 months, 51% and 17%. Conclusions: Patients with advanced/recurrent gastric cancer treated sequentially with a fixed number of courses of S-1 followed by wPTX may have a good chance of treatment continuation. A sequential fixed regimen may further improve survival of patients with advanced/recurrent gastric cancer only with combinations of currently available drugs. No significant financial relationships to disclose.

Immune precipitation with monospecific antiserum was employed to study the intracellular synthesis of viral glycoproteins gp85 and gp37. Labeled gp85 and gp37 were detected from lysates of cells transformed with Rous sacroma virus, strain B77, after long-term labeling with radioactive glucosamine or phenylalanine. Immune precipitates prepared from lysates of cells pulse-labeled for a short time resulted in a glycoprotein of 92,000 molecular weight (gp92). This precursor was stable in B77-transformed Japanese quail cells for several hours, whereas in chicken cells it could be chased within a few hours into virion glycoproteins gp85 and gp37. Similarly, the precursor for the structural viral proteins, pr76, persisted in quail cells much longer than in chicken cells. During very short pulses or in the presence of a glucosamine block (25 mM glucosamine), the antiserum against the viral envelope glycoproteins detected a precursor of higher electrophoretic mobility of approximately 70,000 molecular weight, "p70." Fucose label entered gp92 and gp85 as well as "p70." Proteolytic treatment of virion-bound gp85 in vitro generated two discrete glycoproteins of 62,000 and 45,000 molecular weight, but did not result in an increase in the amount of gp37.

Japanese quails bearing avian sarcoma virus-induced tumors develop immune spleen cells that are cytotoxic in vitro against virally and chemically transformed cells, as well as against embryonic cells. The cell-mediated cytotoxicity can be blocked by soluble antigens extracted from in vitro cultured cells. The existence of partial as well as total blocking effects in tests with extracts from various transformed and untransformed virus-producing cells makes it possible to distinguish up to four different kinds of antigens expressed on sarcoma virus transformed cells: a) a subgroup-specific determinant of the virus-envelope glycoprotein gp85 (s-gp85) is expressed at the surface of productively infected, transformed as well as untransformed cells; b) a group-specific determinant of gp85 (g-gp85) that is only expressed on the surface of virus-transformed cells; c) embryonic antigens, also detectable on chemically transformed as well as on primary normal embryonic cells, and finally; d) a sarcoma virus transformation-specific antigen (TSSA) that is not a structural constituent of the virus.

Ley determinant (Fuc alpha 1----2Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----R) defined by mAb BM-1 is highly expressed in human immunodeficiency virus (HIV)-infected T cell lines and in CD3+ peripheral mature T cells of patients with acquired immune deficiency syndrome (AIDS) or with AIDS-related complex (ARC). Ley expression increased greatly in the CD3+ population in the advanced stage of AIDS when the CD4+ population decreased greatly. Six other carbohydrate antigens tested by their respective mAbs were not detected in these same cells. None of the carbohydrate antigens tested by the seven mAbs used in this study were found in noninfected T cell lines and in normal peripheral blood lymphocytes.

The sterol which was present in two strains of a stable staphylococcal L-form was analyzed by gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry. The retention time of the sterol on gas-liquid chromatography was the same as that of authentic cholesterol. Analysis of the sterol by mass spectrometry showed a molecular ion at an m/e of 386 and the same patterns of major ions above an m/e of 145 as those of authentic cholesterol. As a result, the sterol in staphylococcal L-form was identified as cholesterol. A parent strain and its L-forms were cultured in medium containing [14C]acetate, and the synthesis of cholesterol was examined. In the L-forms, 0.52% of the total lipid radioactivity was found in cholesterol fraction, whereas no significant radioactivity was detected in the cholesterol fraction of the parent strain, indicating that staphylococcal L-forms have acquired the capacity to synthesize cholesterol.

Investigation of the process of cell transformation to malignancy by viruses has been considered for many years now as the most potent approach for elucidating the molecular mechanisms leading to the conversion of cells from normal to malignant patterns of growth. Cells can be transformed by viruses, especially RNA viruses, under strictly reproducible conditions within a short period of time, i.e., 24 h or less. The structure and the replication of these viruses is fairly well understood. Likewise, the genetic makeup and even the gene order of several tumor viruses is known. A gene called “onc” has been identified in avian RNA tumor viruses that does not appear to be involved in the virus replication but rather seems to be specific for the transformation (1, 2).

Transmission of adult T-cell leukemia virus (ATLV) was demonstrated from human lymphoid cell lines carrying ATLV to various non-lymphoid cells accompanied with syncytium formation, which was specifically inhibited by human anti-ATLV sera, indicating that ATLV has cell membrane fusion activity.

From DBT cells persistently infected with mouse hepatitis virus JHM strain (JHM-CC), a cell line producing neither infectious virus nor intracellular viral antigen was obtained after two passages in the presence of antiserum. In addition, 11 cell clones were manipulated from JHM-CC and found to be also free from the virus. These newly obtained cell line and 4 of 11 cell clones were shown to be resistant to JHM and the virus recovered from JHM-CC (JHM-CCV), while the other 7 cell clones were susceptible to both JHM and JHM-CCV as well as vesicular stomatitis virus. The susceptibility of all the cell clones and the newly obtained cell line to JHM and JHM-CCV became higher with passages. The observations were discussed in relation to the viral persistency in JHM-CC.

Spontaneous T-cell leukemia similar to human adult T-cell leukemia (ATL) was found in an African green monkey naturally infected with simian retrovirus closely related to human T-cell leukemia virus type I (HTLV-I). Monoclonal integration of the simian retrovirus was detected in the primary leukemic cells, suggesting an association of the retrovirus with ATL-like leukemia in the monkey.

Human T-cell leukemia virus type I (HTLV-I) is exogenous for human transmission by viral infection and was shown to be a causative agent of adult T-cell leukemia (ATL) in man. Monkeys of several species were found to have antibodies reactive with HTLV-I antigens and thus infection with HTLV-I like retroviruses was suspected. The retroviruses in several species of monkeys were characterized by Southern hybridization, molecular cloning and sequencing. These monkey retroviruses, tentatively called simian T-cell leukemia viruses (STLV), have a genome structure of LTR-gag-pol-env-pX-LTR and are highly homologous with HTLV-I in all regions. A DNA clone of the STLV was isolated from a pig-tailed monkey and the nucleotide sequence was determined. The STLV showed 90% homology in the nucleotide sequence with that of HTLV-I in env-pX-LTR region. This highly homologous sequence indicates that the STLV is a member of the HTLV family but apparently different from HTLV-I. This result excluded the possibility of recent interspecies viral transmission from monkeys to humans, and suggested that STLV can be useful as an animal model in studies on HTLV-I transmission and leukemogenesis in humans. Supporting this suggestion, an African green monkey which was naturally infected with STLV was found to have developed T-cell leukemia that was very similar to human ATL.

Recently, the authors determined the partial sequence of simian immunodeficiency virus (SIV) from the mandrill (SIVMND) and found SIVMND to be a new member of the HIV/SIV group, equidistant from other members, including SIVAGM. Experimentally, the African green monkey and cynomolgus monkey could be infected with SIVAGM and the cottontop tamarin with SIVMND. However, no clinical sign of an AIDS-like disease was observed in these monkeys.

Spleen cells taken from quails treated with chicken alpha-fetoprotein (Ch-AFP) showed reduced natural killer (NK) activity as did spleen cells taken from quails treated with chicken amniotic fluid (ChAmF) in which the presence of Ch-AFP was demonstrated by a gel precipitation test. The Ch-AFP-induced reduction of NK activity was shown to be mediated by suppressor cells. In addition, Ch-AFP-treated quails developed tumors with shorter latent periods than those of the tumors that developed in untreated quails after inoculation with Rous sarcoma virus, as was true for ChAmF-treated quails.

We reported previously that homopolysaccharides with sulfate groups revealed immunomodulating activities--lymphocyte mitogens. We further investigated the role of homopolysaccharides in a different system--cultivation of Molt-4. clone no.8 with supernatant from human T cell lymphotropic virus type III (HTLV-III)-infected TALL-1, utilizing cytopathic effects (CPE), fluorescence antibody technique (FAT), reverse transcriptase (RT) assay and cell proliferation assay. Sulfated homopolysaccharides such as fucoidan, dextran sulfate with three different molecular weights, cellulose sulfate and k-carrageenan showed most potent anti-HTLV-III activities at mitogenic doses. However, neutral homopolysaccharides had no effects on anti-HTLV-III activities Sulfated heteropolysaccharides such a heparin and heparan sulfate had a little effect on anti-HTLV-III activities. It is suggested that sulfate group is most important in inhibiting growth of HTLV-III, but the structure of the polysaccharides is also important, because homopolysaccharides are more potent anti-HTLV-III agents than heteropolysaccharides.