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Biomedical subjects

A Lazo

Publications and source records attributed to A Lazo.

At least 19 recordsLinked to original sources

Induction of latent human cytomegalovirus by conventional gamma irradiation and prevention by treatment with INACTINE PEN110.

BACKGROUND AND OBJECTIVES: Two different leucocyte-inactivation technologies--gamma irradiation and INACTINE PEN110--were evaluated for their effects on cell-associated human cytomegalovirus (CMV). MATERIALS AND METHODS: In vitro CMV-infected cells were spiked into leucoreduced red blood cell concentrates (RCC) or medium at a final concentration of 0.5 - 1 x 10(7) cells/ml to mimic non-leucoreduced levels of leucocytes. The spiked RCC/medium was divided into three equal units and treated with gamma irradiation at the US Food and Drug Administration (FDA)-approved dose of 25 Gy, with 0.1% v/v PEN110 at 22 degrees C for 24 h, or stored at 4 degrees C as a control. The treated and control cells were recovered and tested using infectivity, viability and polymerase chain reaction (PCR) assays. RESULTS: Gamma-irradiated CMV-infected cells produced active virus, as shown by both infectivity assays and PCR quantification of viral DNA. PCR analysis demonstrated higher CMV DNA levels in gamma-irradiated, latently infected monocytic THP-1 cells than untreated control cells. The increased virus production in gamma-irradiated cells was paralleled by an increased metabolic rate and the development of enlarged multinuclear cells. In contrast, PEN110 treatment terminated virus replication and completely inactivated the infected cell. CONCLUSIONS: These results demonstrate that gamma irradiation, at levels currently used to treat RCC, has the capacity to induce expression of CMV, whereas PEN110 inhibits CMV replication and efficiently inactivates the infected cells.

Antiviral Agents↗

Broad-spectrum virus reduction in red cell concentrates using INACTINE PEN110 chemistry.

BACKGROUND AND OBJECTIVES: The risk of transmission of blood-borne pathogens by transfusion is a persistent problem in medicine. To address this safety issue, INACTINE PEN110 chemistry is being utilized to develop a process for preparing pathogen-reduced red blood cell concentrates (RBCC). The purpose of this study was to characterize the virucidal effectiveness of the INACTINE PEN110 chemistry in full units of RBCC by using a panel of viruses with diverse properties in composition, size and shape. MATERIALS AND METHODS: The panel included four enveloped (bovine viral diarrhoea virus, pseudorabies virus, vesicular stomatitis Indiana virus and sindbis virus), six non-enveloped (porcine parvovirus, human adenovirus 2, reovirus 3, vesicular exanthema of swine virus, bluetongue virus, and foot and mouth disease virus) and cell-associated (human immunodeficiency) viruses. All viruses were individually spiked into CPD/AS-1, CP2D/AS-3 and CPD/AS-5 RBCC units and treated with 0.1% PEN110 (vol/vol) at 22 +/- 2 degrees C for up to 22 +/- 2 h. The PEN110 treatment reaction was stopped by chemical quenching, and residual virus was assayed. The cytotoxicity effect of PEN110-treated RBCC on indicator cells and the potential interference with the ability of the virus to infect indicator cells was determined and taken into consideration for calculating the virus-reduction factors, to avoid underestimation or overestimation of the virus reduction. RESULTS: The kinetics of inactivation for viruses spiked into CPD/AS-1, CP2D/AS-3 and CPD/AS-5 RBCC were equivalent. All viruses analysed in this study were reduced to the limit of detection of the assay. The reduction factors for the virus panel ranged from 4.2 to 7.5 log10/ml. CONCLUSIONS: The results from the study demonstrate for the first time that a pathogen-reduction technology for RBCC can achieve a broad-spectrum virucidal effect against both enveloped and non-enveloped viruses. The broad spectrum of virucidal activity of INACTINE PEN110, and equivalent kinetics of virus inactivation in RBCC prepared using different commercially available RBC storage solutions, demonstrate the robustness of this pathogen-reduction process.

Animals↗

Photochemical decontamination of red blood cell concentrates with the silicon phthalocyanine PC 4 and red light.

Various approaches are being developed for virus inactivation of red blood cell concentrates (RBCC) in order to increase the safety of the blood supply. We have been studying the silicon phthalocyanine Pc 4 for this purpose, a photosensitizer activated with red light. Pc 4 targets the envelope of pathogenic viruses such as HIV. To protect RBC during the process two main approaches are used: (i) inclusion of quenchers of reactive oxygen species produced during the treatment. Tocopherol succinate was found to be most effective for this purpose; (ii) formulation of Pc 4, a lipophilic compound, in liposomes that reduce its binding to RBC but not to viruses. As a light source we used a light emitting diode array emitting at 670-680 nm. An efficient mixing device ensures homogenous light exposure during treatment of intact RBCC. Treatment of 50 ml RBCC with 5 microM Pc 4 and 18 J/cm(2) light results in the inactivation of > or = 5.5 log(10) HIV, > or = 6.3 log(10), VSV and > or = 5 log(10) of PRV and BVDV. The relative sensitivities of these viruses based on the slope of virus kill versus light dose are 1.0, 1.25, 1.5 and 1.9 for HIV, VSV, PRV and BVDV, respectively. To achieve the same level of virus inactivation in 350 ml RBCC, the light dose needed is 40 J/cm(2). HIV actively replicating in CEM cells is as sensitive as cell-free and HIV in latently infected cells is 3-4 times more sensitive. Parasites that can be transmitted by blood transfusion (P. falciparum and T. cruzi) are even more sensitive than viruses. Following treatment, RBCC can be stored for 28 days at 4 degrees C with haemolysis below 1%. Previous studies under less favourable conditions showed that baboon RBC circulated with an acceptable 24 hr recovery and half-life. Genetic toxicological studies of Pc 4 with or without light exposure (mutagenicity in bacteria, mammalian cells in vitro and clastogenicity in vivo) were negative. We conclude that a process using Pc 4 and red light can potentially reduce the risk of transmitting pathogens in RBCC.

Animals↗

Virus inactivation by solvent/detergent treatment and the manufacture of SD-plasma.

Solvent/Detergent (SD) is an extraordinarily effective means for eliminating enveloped viruses from plasma and plasma products. The safety margin suggested by the rapid and complete kill of enveloped viruses observed in the laboratory has been confirmed repeatedly by groups worldwide and by thirteen years of routine clinical use encompassing an estimated 35 million doses of a wide variety of products. Throughout this time, there has not been a single documented case of enveloped virus transmission by an SD-treated product. This record of safety spawned the development of SD-treated plasma as a substitute for fresh frozen plasma (FFP) and has encouraged the adoption of SD for the treatment of non-blood products such as monoclonal antibodies and those derived from recombinant DNA procedures. This review summarizes the use of SD treatment, including its use in combination with other viral elimination procedures, and also summarizes Vitex's initial experience in the manufacture of SD-Plasma, recently licensed by the U.S. FDA.

Blood-Borne Pathogens↗

Constitutive cytokine release by simian T-cell lymphotrophic virus type I (STLV-I) and human T-cell lymphotrophic virus types I/II (HTLV-I/II) transformed cell lines.

Simian T-cell lymphotrophic virus type I (STLV-I) and human T-cell lymphotrophic virus types I/II (HTLV-I/II) contain the tax gene which can transactivate the transcription of viral and cellular genes including several cytokines. These investigations used two STLV-I and four different HTLV-I/II transformed cell lines to quantitate constitutive cytokine release, p24 antigen production, and to correlate gag p24 antigen and cytokine release. These investigations are the first to report 1) quantitative comparison of constitutive release of multiple cytokines by several STLV-I and HTLV-I/II transformed cell lines and to determine the cytokines constitutively released by STLV-I transformed cell lines as IL-6, b-FGF, and GM-CSF (and TNF-beta, and PDGF in a higher viral producing line); 2) statistically significant differences in levels of cytokines produced by STLV-I and HTLV-I/II transformed cell lines, dependent on the method of results quantification; and 3) a correlation between levels of STLV-I and HTLV-I/II and gag p24 antigen production and cytokine production.

Animals↗

Immune recognition of genetically diverse simian T-cell lymphotropic virus type I isolates.

Nucleotide sequence analysis of selected regions of the gag, pol, env and pX genes of simian T-cell lymphotropic virus type I (STLV-I) strains indicated that African isolates were more closely related to human T-cell lymphotropic virus type I (HTLV-I) than Asian isolates. Despite these recent comparative studies on nucleotide sequence homology between HTLV-I and STLV-I isolates, only limited information is available regarding the influence of genetic differences on antigen-antibody recognition of distinct STLV-I strains. In this study, we demonstrated that sera from STLV-I-infected yellow baboons (Papio cynocephalus) reacted strongly with env gp62/68 from HTLV-I-infected cell lines MT-2 and C10/MJ. In contrast, sera from Japanese macaques (Macaca fuscata) naturally infected with Asian STLV-I had weak reactivity to env gp62/68 of these prototypic HTLV-I strains. Pst-1 restriction enzyme analysis of proviral DNA indicated that the baboon virus isolates were more closely related to HTLV-I than the Japanese isolates. These results indicate that nucleotide sequence diversity, correlates with variations in proviral restriction enzyme sites and antibody recognition of viral envelope proteins. These differences in immunoreactivity may have important implications for serologic diagnosis, as well as epidemiological and vaccine studies of STLV-I infection.

Animals↗

Comparison of constitutive cytokine release in high and low histologic grade AIDS-related Kaposi's sarcoma cell strains and in sera from HIV+/KS+ and HIV+/KS- patients.

Kaposi's sarcoma (KS) is both an AIDS-defining disease and the most common HIV-associated malignancy. A cytokine-mediated pathogenesis for AIDS-KS is implicated because AIDS-KS-derived cell strains both respond to and express a variety of cytokines. We have reported the establishment of several (n = 18) AIDS-KS cell strains and determined that reduced exogenous growth factors are necessary to sustain proliferation in isolates from high histologic grade KS lesions. This current investigation explored the possibility that there are histologic grade-associated differences in either the qualitative and/or quantitative constitutive release of AIDS-KS growth stimulatory cytokines. Our findings showed that the incorporation of HTLV-II cytokine-rich conditioned media induced both qualitative and significant quantitative cytokine release, suggesting that exogenous growth promoters stimulate constitutive cytokine release. ELISA of our AIDS-KS cell strains demonstrated constitutive release of IL-6 (seven of seven), FGF-2 (five of seven), GM-CSF (three of seven), and IL-1 beta (one of seven). None of our AIDS-KS cell strains constitutively released detectable levels of Onco-M, IL-4, PDGF, TNF-alpha, or TNF-beta. In addition, we report that the method of cytokine result quantitation significantly affects reported cytokine levels. We determined that there was no significant histologic grade-dependent difference in the constitutive release of soluble cytokines by in vitro grown cultures of AIDS-KS cells. The presence of HIV influenced the sera cytokine profiles by elevating IL-6 and decreasing PDGF concentrations of HIV+ individuals relative to HIV- healthy controls. However, the presence of KS was not associated with unique serum cytokine profiles, because no differences were noted in comparisons of HIV+/KS+ versus HIV+/KS- individuals. Our findings suggest that the local environment is key in modulating AIDS-KS cytokine expression and that KS growth-promoting factors function at the local or paracrine, not the systemic, level. In conclusion, our previous results demonstrated a histologic grade-associated difference in the in vitro growth capacity of AIDS-KS cells; with high histologic grade isolates displaying a marked growth advantage during culture in minimally supplemented media. Findings from this current study reveal that although the potential for a constitutive growth loop exists in the high-grade isolates, it is not reflected in the free levels of soluble cytokines secreted into the culture medium.

Acquired Immunodeficiency Syndrome↗

Correlation between AIDS-related Kaposi sarcoma histological grade and in vitro behavior: reduced exogenous growth factor requirements for isolates from high grade lesions.

Kaposi sarcoma, the most common AIDS-associated malignancy, affects 10-30% of all AIDS patients. To date, research into the biological characteristics of AIDS-related Kaposi sarcoma (AIDS-KS) derived cell lines has been based on cultures established from skin explants or pleural effusions/peritoneal fluids. We have established several AIDS-KS lines from biopsy confirmed oral mucosal and epidermal AIDS-KS lesions and have found a correlation between AIDS-KS lesional grade and in vitro cellular growth characteristics. In comparison to epidermal AIDS-KS lesions, mucosal AIDS-KS lesions frequently possessed both a more advanced histologic grade and demonstrated a greater capacity to proliferate in minimal medium. We report the ability of AIDS-KS isolates from high grade lesions to sustain proliferation (greater than 60 population doubling levels) in medium not supplemented with endothelial cell growth supplement and/or cytokine rich conditioned medium. These findings indicate that AIDS-KS cells isolated from high grade lesions have reduced requirements for exogenously provided growth supplements, and suggest that increased autologous cytokine production accompanies AIDS-KS lesional progression.

Acquired Immunodeficiency Syndrome↗

Anomalous intracranial venous drainage mimicking orbital or cavernous arteriovenous fistula.

A 9-year-old child presented with right eye swelling and bluish discoloration over the periorbital region. MR and CT displayed prominent vessels within the orbit and in the facial region, suggesting a carotid-cavernous fistula. Doppler ultrasound indicated the vascular engorgement was not secondary to a proximal arteriovenous shunt. Arteriography with its inherent time sequence image capability prompted the proper diagnosis of bilateral atresia of the sigmoid sinuses.

Arteriovenous Fistula↗

Genetic analysis and molecular phylogeny of simian T-cell lymphotropic virus type I: evidence for independent virus evolution in Asia and Africa.

Type C retroviruses, designated simian T-cell lymphotropic virus type I (STLV-I), have been isolated from several genera of Old World monkeys and apes, but not from New World monkeys and prosimians. To determine the genomic diversity and molecular evolution of STLV-I and to clarify their genetic relationship to human T-cell lymphotropic virus type I (HTLV-I), we enzymatically amplified, then directly sequenced selected regions of the gag, pol, env, and pX genes of STLV-I strains from Asia and Africa. STLV-I strains Si-2, Matsu, and JM86 from Japanese macaques, which exhibited sequence similarities ranging from 98.5 to 99.8% among themselves, diverged by 12.9 to 13.3% from STLV-I strain MM39-83 from a naturally infected rhesus macaque, by 9.7 to 11.2% from STLV-I strains from Africa, and by 8.8 to 11.2% from HTLV-I strains originating in Japan, India, Africa, the Caribbean, the Americas, Polynesia, and Melanesia. By contrast, the interspecies nucleotide sequence similarity among African STLV-I strains from green monkey, yellow baboon, sooty mangabey, and common chimpanzee was remarkably high, ranging from 96.9 to 97.4%, and these STLV-I strains diverged by only 2.2 to 2.8% from HTLV-I strain EL from equatorial Zaire. Phylogenetic trees constructed by using the neighbor-joining and maximum parsimony methods indicated that the Asian STLV-I strains diverged from the common ancestral virus prior to African STLV-I and cosmopolitan and Melanesian HTLV-I strains. Thus, our data are consistent with an archaic presence of STLV-I in Asia, probably predating macaque speciation, with subsequent independent virus evolution in Asia and Africa.

Africa↗

Cultured AIDS-related Kaposi's sarcoma cells retain a proliferative bioenergetic profile but demonstrate reduced cytoprotective capabilities.

Features of AIDS-related Kaposi's sarcoma (AIDS-KS), such as the multifocal presentation at mucosal and epidermal sites subjected to trauma, suggest that AIDS-KS is initially a reactive hyperplasia that subsequently progresses to a neoplasia. It is recognized that there is an association between sustained inflammatory states and the subsequent development of neoplasia (e.g., ulcerative colitis/colonic adenocarcinoma). Furthermore, patients who develop AIDS-KS experience both a constant immune stimulation due to sustained high levels of virus-induced cytokines and, because of a sparing effect on their phagocytic cells, retention of the phagocytic inflammatory response. A component of phagocytic activation is the initiation of the oxidative burst, resulting in the generation of reactive oxygen species (ROS), which can be mutagenic to host cells if released beyond the phagolysosome and not inactivated. Our results demonstrate that cultured AIDS-KS cells possess decreased cytoprotective capabilities. Relative to either dermal fibroblasts, or human microvascular endothelial cells (HMECs), AIDS-KS cells contained significantly lower levels of glutathione, a tripeptide integral in both cytoprotection and maintenance of cellular thiol status. While HMECs increased catalase activity during culture in the cytokine-rich KS milieu (control medium supplemented with conditioned medium from MOT, an HTLV II-infected cell line), AIDS-KS cells demonstrated reduced catalase function under these conditions. Furthermore, HMEC cultures showed an inherent biochemical responsiveness, by increasing catalase activity following exposure to exogenous H2O2. In contrast, the catalase activity of AIDS-KS cells decreased following H2O2 challenge. Our results show that an inherent deficiency in cellular cytoprotection is present in AIDS-KS cells and suggest that oxidant stress may function in the development and progression of AIDS-KS.

Acquired Immunodeficiency Syndrome↗

Lack of evidence for human T cell lymphotrophic virus type I or II infection in patients with systemic lupus erythematosus or rheumatoid arthritis.

OBJECTIVE: Human retroviruses including human immunodeficiency virus (HIV) and human T cell lymphotrophic virus Types I and II (HTLV-I/II) have been associated with forms of connective tissue autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We looked for evidence of HTLV-I/II infection in a large population of SLE, RA, and control patients. METHODS: One hundred fifteen patients with connective tissue autoimmune disease and other rheumatological disorders were screened for antibodies to HTLV-I/II by Western immunoblots (WIB). Due to the transforming characteristic of these retroviruses, the patients' peripheral blood mononuclear cells (PBMNC) were cultured in attempts to establish continuous cell lines. Furthermore, PBMNC culture supernatants were analyzed for reverse transcriptase activity and/or HTLV-I/II gag antigen production. The presence of HTLV-I/II proviral sequences in short term culture and fresh PBMNC was determined by Southern blot analysis and polymerase chain reaction (PCR), respectively. respectively. RESULTS: All 115 patients were HTLV-I/II and HIV seronegative. Seventy-four attempts to establish PBMNC cell lines from 65 patients were unsuccessful with a mean culture survival time of 3.6 (+/- 1.4) months. Reverse transcriptase activity and HTLV-I/II gag antigen production were not detected in 51 and 16 culture supernatants tested, respectively. Cells from 11 patients tested by Southern blot analysis and from 57 patients tested by PCR were negative for HTLV-I/II related sequences. CONCLUSION: Our results failed to establish an association between human retroviruses (HTLV-I/II and HIV) and SLE, RA, or other rheumatological disorders. However, these results do not rule out other exogenous or endogenous retroviruses that may play a role in the initiation and/or promotion of these diseases.

Adolescent↗

Sexual transmission of simian T-lymphotropic virus type I: a model of human T-lymphotropic virus type I infection.

Simian T-lymphotropic virus type-I (STLV-I) seronegative females placed together with seropositive males for breeding purposes were followed from 1984-1990 to determined seroconversion rates by enzyme immunoassay and western immunoblot analysis. Two of 26 females and 1 of 4 males previously negative for antibodies to STLV-I seroconverted during the study period. Statistical analysis of sexual encounters indicated that the probability of a seronegative female testing positive for STLV-I after a sexual encounter with a seropositive male is less than 4%. These data indicate that even though sexual contact is important in the transmission of STLV-I, it may not be an efficient mode of viral infection. These data also suggest that female-to-male transmission of STLV-I occurs, as recently reported for human T-lymphotropic virus type-I (HTLV-I) infection. These results are important because HTLV-I and STLV-I share many features in common including routes of viral transmission. In addition, the difficulty of clearly quantitating the risk of sexual transmission in humans makes the primate animal model a valuable alternative to study the human infection.

Animals↗

Environmental induction of tumor phenotype in a putative Kaposi sarcoma progenitor cell.

Many features of AIDS-related Kaposi sarcoma (AIDS-KS), e.g., multifocal lesional presentation at sites perfused by the microvasculature, suggest that AIDS-KS is initially a hyperplasia that subsequently progresses to a neoplasia. We propose that the unique AIDS environment, which contains high levels of circulating factors such as viral cytokines, is key in initiating the KS lesion. Further, we maintain that due to their physiological function, human microvascular endothelial cells (HMECs) are both likely target cells for the AIDS-related cytokines, and are putative AIDS-KS progenitor cells. Previously, we have shown that as a component of HMEC transition between proliferative and differentiated growth, HMECs modulate their nucleotide and glutathione levels. After attaining contact inhibition, HMECs enter a state of differentiation, which is characterized by cellular entrance into a G0, quiescent growth state, a decrease in cellular bioenergetic profiles, and spontaneous formation of microtubules. In contrast, when cultured in a "KS milieu", HMECs fail to differentiate. Instead, the "KS milieu" cultured cells assume a "growth relaxed" phenotype and demonstrate a lack of contact inhibition, loss of anchorage dependence, and retention of a "proliferative" bioenergetic profile despite culture confluence. Our results imply both that HMECs are responsive to AIDS-related cytokines, and that the local environment is key to instigating a relaxation of cellular growth controls.

AIDS-Related Complex↗

Fusion activity dissociated from replication ability in feline immunodeficiency virus (FIV) in human cells.

Multinucleated-giant-cell formation followed by cell killing was observed after cocultivation of the feline immunodeficiency virus (FIV)-producing feline T-cell line 3201/FIV with various human cells, including T-cell lines carrying human T-cell lymphotropic virus type I (HTLV-I). The susceptibility to giant cell formation varied with the cell lines tested. Cocultivation of irradiated 3201/FIV cells with MT-2 cells resulted in giant cell formation as early as 2 h in culture, with striking resemblance to that induced by human immunodeficiency virus (HIV). MT-4 cells (HTLV-I positive) and H9 cells (HTLV-I negative) were less susceptible than MT-2 to the induction of syncytia. MOLT-4 cells (HTLV-I negative) had intermediate sensitivity to syncytia formation. No syncytia were observed in the monocytic cell line U-937 (HTLV-I negative). Syncytia formation between 3201/FIV and MT-2 cells was inhibited by polyclonal cat anti-FIV antisera but not polyclonal cat anti-feline leukemia virus (FeLV) antisera, goat anti-FeLV, uninfected specific-pathogen-free cat serum, human anti-HTLV-I antisera, or normal human and goat serum. Concentrated cell-free FIV supernatant from 3201/FIV also induced giant cells of MT-2 cells that were indistinguishable from those induced by cocultivation. Giant cells and extensive cell killing associated with giant cell formation declined and disappeared within 10 days. Surviving cells appeared to be of normal size and grew continuously without expressing FIV antigen or releasing infective virus. Although Southern blot analysis using probes specific for FIV could not detect proviral DNA in any of the five human cell lines cocultured with irradiated 3201/FIV cells, the polymerase chain reaction (PCR) technique detected FIV-specific DNA in MOLT-4 cells. DNA from the FIV-PCR positive MOLT-4 cells was PCR negative for endogenous FeLV-specific sequences, indicating that the MOLT-4 cell DNA was not contaminated with DNA from feline cells (i.e., 3201 cells). The FIV-MOLT-4 cells remained PCR positive for FIV after 40 passages, suggesting stable integration in the human cell line. These findings indicate that FIV is capable of forming proviral DNA in human T-lymphoid cells by cocultivation, although this FIV-carrying human cell line failed to produce replication-competent viruses.

Animals↗

Detection of simian T-lymphotropic virus type I using the polymerase chain reaction.

To develop the polymerase chain reaction (PCR) for the detection of simian T-lymphotropic virus type I (STLV-I) infection, cell lines or peripheral-blood mononuclear cells (PBMC) from 2 non-human primate species [African green monkeys (AGM), Cercopithecus aethiops; baboon, Papio cynocephalus] were evaluated for their STLV-I status using oligonucleotide primer pairs and probes specific for the tax and pol gene regions of the closely related human T-lymphotropic virus type I (HTLV-I). These PCR results were compared with serologic (Western blot assay) and viral culture (p24-antigen capture assay) data. PCR products for both gene regions were detected in established baboon, Japanese macaque and rhesus macaque STLV-I-producing cell lines. STLV-I tax and pol products were also detected in PBMC from 4 of 4 infected AGM and 4 of 4 infected baboons, each of which were also Western-blot-positive and p24-antigen-capture-positive. Of the remaining AGM (n = 7) and baboon (n = 1) which were PCR-negative, each was also Western-blot-negative and p24-antigen-capture-negative. Two seronegative and virus-culture-negative AGM were classified as PCR indeterminate with weak reactivity using tax primers. These primer pairs failed to amplify DNA from uninfected human PBMC, an uninfected human lymphoid cell line, a simian immunodeficiency virus macaque (SIVmac251)-infected cell line and a simian-retrovirus-type-D(SRV-D)-infected cell line. HTLV-II-pol-specific primer pairs failed to amplify DNA from STLV-I-infected cell lines and PBMC from STLV-I-infected monkeys. Further, HTLV-I pol and tax primer pairs successfully amplified RNA from HTLV-I- and STLV-I-infected cell lines by reverse transcriptase (RT)-PCR. We have demonstrated excellent specificity in the detection of STLV-I by PCR using these HTLV-I-derived primers and probes. Additionally, our data suggest that the tax and pol gene regions are conserved between HTLV-I and STLV-I strains found among these diverse species of non-human primates.

Animals↗

Osseous regeneration after therapy in patients with head and neck tumors.

Four patients with head and neck tumors were observed by serial computed tomography (CT) during treatment. Osseous regeneration was demonstrated at sites of initial osteolytic destruction in two patients who responded to therapy. This regeneration was observed at 4 and 7 months, respectively, after the start of therapy. No such regeneration could be seen in the other two patients who did not respond to treatment. CT may be useful not only in demonstrating initial osseous invasion, but also in monitoring treatment response.

Adult↗

A monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset.

Anti-double-stranded DNA antibodies are commonly found in the serum of patients with systemic lupus erythematosus (SLE). They are a heterogeneous group of antibodies thought to differ in pathogenicity. The degree of heterogeneity and the structural correlates of pathogenicity, however, remain poorly defined. To address these questions we have been generating anti-idiotypic antibodies to the anti-DNA antibodies found in the serum of SLE patients. In this paper we report the generation and characterization of a new murine monoclonal anti-idiotype, 8.12, that recognizes a subset of anti-DNA antibodies that is present in serum of approximately 50% of patients with SLE. The 8.12 anti-idiotype recognizes uniquely cationic anti-DNA antibodies, all of which express lambda light chains. In murine models of SLE, it has been suggested that cationic anti-DNA antibodies are preferentially deposited in the kidney. It may be, therefore, that 8.12 recognizes a subset of anti-DNA antibodies of particular pathogenic significance.

Antibodies, Anti-Idiotypic↗