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1.
Exp Oncol ; 37(1): 23-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25804227

ABSTRACT

AIM: To evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphthal-NU, 2-chloroethylnitrosourea compounds with substituted naphthalimide in the pre-clinical studies. MATERIALS AND METHODS: In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo anti-tumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlich's carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4(+), CD8(+) and CD25(+) cells in treated mouse were also examined. RESULTS: Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4(+) and CD8(+) T cells and down regulate CD4(+)CD25(+) regulatory T cells. CONCLUSION: Overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Ethylnitrosourea/analogs & derivatives , Naphthalimides/chemistry , Naphthalimides/therapeutic use , Neoplasms/drug therapy , Animals , CD4 Antigens/analysis , CD8 Antigens/analysis , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/pathology , Cell Line, Tumor , Ethylnitrosourea/chemistry , Ethylnitrosourea/therapeutic use , Humans , Interleukin-2 Receptor alpha Subunit/analysis , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Male , Mice , Neoplasms/pathology , Sarcoma 180/drug therapy , Sarcoma 180/pathology
2.
Mol Immunol ; 59(2): 119-27, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24607970

ABSTRACT

Tumor-associated macrophages (TAMs) are preferentially M2 skewed and promote tumor growth, angiogenesis, invasion, and/or metastasis. In this study, we have analyzed the in vitro immunomodulatory potential of a non-toxic neem leaf glycoprotein (NLGP) in reprogramming Stage III supraglottic laryngeal tumor cell lysate (SLTCL) induced M2 TAMs to their classical anti-tumor shape (M1). Data generated from this study support that NLGP is effective in preventing the SLTCL induced generation (CD68(+)CD206(+)IL-10(high) to CD68(+)CD206(-)IL-10(low) TAMs) and functions (NO(low) to NO(high), MHC-I(low) to MHC-I(high), CD80(low) to CD80(high)) of pro-tumorous M2 macrophages, which in turn associated with sustained anti-tumor effector functions by promoting cytotoxic T cell activities and suppressing regulatory T cells. Furthermore, our data also suggest that NLGP prevents M2 skewness of TAMs by downregulating phosphorylation of targeted STAT3.


Subject(s)
Azadirachta/chemistry , Glycoproteins/pharmacology , Immune Evasion/drug effects , Immunologic Factors/pharmacology , Laryngeal Neoplasms/immunology , Macrophages/drug effects , Plant Leaves/chemistry , STAT3 Transcription Factor/metabolism , Cell Line, Tumor , Down-Regulation/drug effects , Humans , Interleukin-10/biosynthesis , Interleukin-12/biosynthesis , Macrophages/immunology , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/biosynthesis , Phosphorylation , Plant Extracts/pharmacology , RNA Interference , RNA, Small Interfering , STAT3 Transcription Factor/genetics , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Regulatory/immunology
4.
Pathobiology ; 64(3): 131-5, 1996.
Article in English | MEDLINE | ID: mdl-8910921

ABSTRACT

A recent study suggested that a significant portion of the oligoclonal IgG found in multiple sclerosis (MS) cerebrospinal fluid may be removed by absorption with simian virus 5 (SV5). We have now evaluated the proliferative responses to SV5 generated by peripheral blood mononuclear cells from normal adult subjects and from patients with MS. Positive responses were detected in 16 of 16 subjects in each group. The magnitude of the response was not significantly different in the two groups. There was no correlation between the level of response and the presence or absence of HLA-DR2. No cross-reactivity with SV5 was demonstrated by panels of human T cell clones directed against myelin basic protein or measles virus. More than 60% of normal individuals between 10 and 16 years of age also generated positive T cell proliferative responses to SV5, while fewer than 25% of subjects below the age of 6 generated positive responses. Intermediate percentages of positive responders were detected in subjects 6-9 years of age. We conclude that the adult human population has been widely exposed to this organism and that initial exposure generally occurs in the early to middle school-age years.


Subject(s)
Multiple Sclerosis/immunology , Respirovirus/classification , Respirovirus/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Lymphocyte Activation/immunology , Viral Proteins/immunology
5.
AIDS ; 5(7): 797-803, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1892587

ABSTRACT

The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag, pol, and env) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.


Subject(s)
HIV Seropositivity/cerebrospinal fluid , HIV-1/isolation & purification , Nervous System Diseases/cerebrospinal fluid , Polymerase Chain Reaction , RNA, Viral/cerebrospinal fluid , Adult , Base Sequence , Cohort Studies , Deoxyribonucleotides , Female , HIV Seropositivity/complications , HIV Seropositivity/epidemiology , Homosexuality , Humans , Male , Middle Aged , Molecular Sequence Data , Nervous System Diseases/complications , Prospective Studies
6.
J Med Virol ; 33(2): 106-13, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1711092

ABSTRACT

The CSF/serum immune response to HIV 1 was studied in 24 patients admitted for investigation. The level of antibody to HIV-1 and specificity of oligoclonal IgG were determined in blood and cerebrospinal fluid (CSF). The majority of patients demonstrated elevated levels of intrathecal IgG synthesis, with levels of HIV-1-specific antibody frequently being significantly higher in CSF than in serum. In 16 of 21 patients the CSF/serum antibody ratio indicated active intrathecal synthesis. Oligoclonal banding was present in CSF from all 24 patients. Immunoprinting of serum and CSF demonstrated antigenic specificity (p24, gp 160, RT) of the clonal antibodies in all of 12 patients though the patterns of reactivity in CSF did not necessarily correspond with that of serum. Although a specific association of particular patterns with HIV CNS disease was not found we feel that these markers should be included in longitudinal studies of HIV-related diseases of the CNS. The specificity of oligoclonal antibodies, both in CSF and in serum was demonstrated, and this specificity may be a useful marker for longitudinal studies in HIV-1 antibody-positive asymptomatic patients.


Subject(s)
AIDS Dementia Complex/immunology , Acquired Immunodeficiency Syndrome/immunology , HIV Antibodies/biosynthesis , HIV-1/immunology , Immunoglobulin G/biosynthesis , Immunoglobulins/biosynthesis , AIDS Dementia Complex/complications , Acquired Immunodeficiency Syndrome/complications , Adult , Epitopes , Female , HIV Antibodies/cerebrospinal fluid , HIV Antigens/immunology , Humans , Immunoglobulin G/cerebrospinal fluid , Immunoglobulins/cerebrospinal fluid , Injections, Spinal , Male , Oligoclonal Bands
8.
J Gen Virol ; 68 ( Pt 11): 2769-80, 1987 Nov.
Article in English | MEDLINE | ID: mdl-2445904

ABSTRACT

Hybridomas secreting monoclonal antibodies to simian virus 5 (SV5) were obtained following immunization of mice with purified preparations of a human isolate (LN) of SV5. Immune precipitation studies showed that these monoclonal antibodies had specificities for the haemagglutinin-neuraminidase (HN), fusion (F), nucleo-, matrix and phospho- (P) proteins of SV5. By use of a radioimmune competition assay the monoclonal antibodies to the HN protein were assigned to four groups, members of which recognized different antigenic sites on the protein. All the anti-HN antibodies and the anti-F antibody neutralized virus infectivity. The 54 monoclonal antibodies obtained were used to determine whether there were antigenic differences between five human, two canine and one simian isolate of SV5. Although most of the monoclonal antibodies reacted with all isolates, a few did reveal antigenic differences in the HN, F and P proteins. Furthermore, analysis by SDS-PAGE showed that while the electrophoretic mobilities of most of the virus polypeptides of these isolates were similar some differences could be detected. In particular the P protein showed the most marked mobility differences between the human, canine and simian isolates. Slight differences in the mobility of the F1 glycoprotein could also be visualized.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Viral/analysis , Respirovirus/immunology , Animals , Antibody Specificity , Dogs/microbiology , Epitopes , HN Protein , Haplorhini/microbiology , Humans , Molecular Weight , Neutralization Tests , Respirovirus/classification , Viral Envelope Proteins/immunology , Viral Proteins/immunology
9.
Nature ; 327(6119): 244-7, 1987.
Article in English | MEDLINE | ID: mdl-3553964

ABSTRACT

Multiple sclerosis is a demyelinating disease of the central nervous system and although there is little doubt that an infectious agent (or agents) is involved it has not been possible to demonstrate this unequivocally by any direct relationship to a given agent. Here we show that a significant proportion of patients with multiple sclerosis have antibodies against the paramyxovirus SV5 (simian virus 5) in their cerebrospinal fluid and in some of these such antibodies form a major proportion of the total immunoglobulin content. Further, we have been able to demonstrate that the oligoclonal bands displayed on electrophoresis of the cerebrospinal fluid of these patients can be removed by prior absorption with SV5 virus antigen.


Subject(s)
Antibodies, Viral/cerebrospinal fluid , Multiple Sclerosis/immunology , Paramyxoviridae/immunology , Antigens, Viral , Centrifugation , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique , Humans , Immunoglobulins/cerebrospinal fluid , Immunosorbent Techniques , Measles virus/immunology
10.
J Gen Virol ; 66 ( Pt 10): 2103-10, 1985 Oct.
Article in English | MEDLINE | ID: mdl-2995550

ABSTRACT

The fluorescent antibody technique using both monoclonal and specific polyclonal virus antibodies was applied to investigate the nature of the inclusions seen in the abnormal osteoclasts associated with Paget's bone disease. The results show that antigens of measles virus, simian virus 5 (SV5) and human parainfluenza virus type 3 (PF3) could be detected in the osteoclasts but not in control bone cells. Measles and SV5 nucleoprotein (NP) and haemagglutinin-neuraminidase (HN) antigens were apparently present in all the cases of Paget's disease examined, whereas PF3 NP and HN antigens were present only in some of the cases. These investigations suggest that paramyxoviruses may play a role in the aetiology of the bone disease.


Subject(s)
Antigens, Viral/analysis , Osteitis Deformans/immunology , Osteoclasts/immunology , Paramyxoviridae/immunology , Antibodies, Monoclonal , Antibodies, Viral , Fluorescent Antibody Technique , Hemagglutinins, Viral/analysis , Humans , Measles virus/immunology , Mumps virus/immunology , Neuraminidase/analysis , Nucleoproteins/analysis , Osteitis Deformans/microbiology , Osteoclasts/microbiology , Parainfluenza Virus 3, Human/immunology , Respiratory Syncytial Viruses/immunology , Viral Proteins/analysis
11.
J Neuroimmunol ; 9(1-2): 99-108, 1985 Jul.
Article in English | MEDLINE | ID: mdl-3891785

ABSTRACT

A monoclonal antibody against simian virus (SV5) HN glycoprotein which specifically neutralises the virus cross-reacts in immunofluorescence with an antigen in the cytoplasm of Purkinje cells of adult rat brain. After fixation in acetic acid-ethanol a cross-reaction is also seen with a myelin component. Cross-reaction of this antibody with human brain was also observed on section using immunofluorescence and in tissue extracts using ELISA and radioimmune assays. Monoclonal antibodies against other viruses, against another epitope on the same virus polypeptide and against another SV5 polypeptide of the same isotype were all negative in these tests.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Viral/immunology , Antigens/immunology , Brain/immunology , Animals , Cross Reactions , Fluorescent Antibody Technique , Humans , Paramyxoviridae/immunology , Rats
12.
J Gen Virol ; 65 ( Pt 11): 1881-8, 1984 Nov.
Article in English | MEDLINE | ID: mdl-6389770

ABSTRACT

Human bone marrow cells derived from multiple sclerosis (MS) and control patients were screened for a number of virus antigens by the fluorescent antibody technique using monoclonal antibodies. The results showed that antigens of the paramyxovirus, simian virus 5, were present in about 60% of MS and 25% of control bone marrows. About 25% of the MS and 50% of control bone marrows were found to contain nucleoprotein antigen of the human parainfluenza types 1 and 3. These experiments demonstrated that paramyxoviruses can persist in human tissues possibly in a defective or repressed state.


Subject(s)
Bone Marrow/microbiology , Multiple Sclerosis/microbiology , Paramyxoviridae/isolation & purification , Animals , Antibodies, Monoclonal , Antigens, Viral/analysis , Cells, Cultured , Chlorocebus aethiops , Fluorescent Antibody Technique , Humans , Kidney
13.
J Gen Virol ; 65 ( Pt 8): 1295-303, 1984 Aug.
Article in English | MEDLINE | ID: mdl-6205118

ABSTRACT

Simian virus 5 (SV5) isolates derived after co-cultivation of human bone marrow aspirates of multiple sclerosis (MS) patients were shown by immunoprecipitation, cross-neutralization and haemagglutination inhibition techniques to be similar antigenically but not identical to the prototype strain. Analyses of human sera (MS and control) showed that about 20% contained neutralizing antibodies to SV5 and immunoprecipitated the specific SV5 HN polypeptide. A competition assay using a specific SV5 monoclonal antibody confirmed that a human serum containing such neutralizing activity also blocked a specific SV5 epitope whereas another human serum with demonstrable antibodies to the related human parainfluenza virus type 2 did not block this epitope. These tests therefore suggested that SV5 can infect humans. However, there was no indication, on the basis of these tests, of any aetiological relationship of the SV5 infection to the induction of MS.


Subject(s)
Multiple Sclerosis/microbiology , Paramyxoviridae/classification , Respirovirus/immunology , Antibodies, Viral/immunology , Antigens, Viral/analysis , Antigens, Viral/immunology , Bone Marrow/microbiology , Cross Reactions , Epitopes , Humans , Molecular Weight , Paramyxoviridae/immunology
14.
J Gen Virol ; 64 (Pt 9): 2069-72, 1983 Sep.
Article in English | MEDLINE | ID: mdl-6193248

ABSTRACT

Monoclonal antibodies to the haemagglutinin-neuraminidase (HN), fusion (F), polymerase and nucleocapsid polypeptides of Newcastle disease virus were prepared. Two epitopes were recognized on the HN polypeptide: one was associated with inhibition of haemagglutination and poor neutralization and the other with good neutralization and no inhibition of haemagglutination. The most effective neutralizing antibody was that produced against the F polypeptide. The poorer neutralization associated with the antibody against the HN epitope was augmented by antiglobulin or complement. The monoclonal antibodies that inhibited haemagglutination also inhibited neuraminidase activity when fetuin but not neuraminyl lactose was the substrate.


Subject(s)
Antibodies, Monoclonal/analysis , Antibodies, Viral/analysis , Newcastle disease virus/immunology , Epitopes/analysis , Hemagglutination, Viral , Neuraminidase/immunology , Neutralization Tests , Peptides/immunology
15.
J Gen Virol ; 64 (Pt 8): 1663-72, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6192203

ABSTRACT

Monoclonal antibodies against the major glycoprotein (HN) and the nucleoprotein (NP) of paramyxovirus SV5 and human paramyxovirus (PF) type 3 have been obtained. Two different epitopes have been detected on the SV5 HN polypeptide, one being specific to SV5 and the other also cross-reacting with PF-2 HN polypeptide. Monoclonal antibody against SV5 NP polypeptide also reacted with PF-2 NP polypeptide. Similar epitopes showing both specific and group cross-reactions were detected with PF-3 HN and NP monoclonal antibodies against PF-3 and Sendai viruses. No cross-reactions were detected between these two groups of paramyxoviruses.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Viral/immunology , Paramyxoviridae/immunology , Viral Proteins/immunology , Cross Reactions , Epitopes/immunology , Fluorescent Antibody Technique , HN Protein , Hybridomas , Neutralization Tests , Nucleoproteins/immunology , Precipitin Tests , Radioimmunoassay
16.
J Gen Virol ; 60(Pt 1): 177-83, 1982 May.
Article in English | MEDLINE | ID: mdl-6178797

ABSTRACT

Using the technique of immune precipitation of [35S]methionine-labelled infected cell polypeptides followed by SDS-polyacrylamide gel electrophoresis and autoradiography it has been shown that SV5 and a closely related isolate are both antigenically related to human parainfluenza virus type 2. Limited cross-reactions were also demonstrated between parainfluenza virus types 1 and 3 by this method and the apparent molecular weights of the major structural components of human parainfluenza virus types 2 and 3 have been deduced.


Subject(s)
Antigens, Viral/immunology , Paramyxoviridae/immunology , Respirovirus/immunology , Cross Reactions , Epitopes , Glycoproteins/immunology , Nucleoproteins/immunology , Parainfluenza Virus 1, Human/immunology , Parainfluenza Virus 2, Human/immunology , Precipitin Tests , Viral Proteins/immunology
18.
Lancet ; 2(8086): 387-91, 1978 Aug 19.
Article in English | MEDLINE | ID: mdl-79758

ABSTRACT

Bone-marrow aspirates from 5 patients with recent episodes of multiple sclerosis (M.S.) contained increased numbers of plasma cells, and aspirates from 3 of these patients contained atypical reticulum cells. When bone-marrow from 4 of the patients was inoculated into cell cultures a cytopathic effect (C.P.E.) was observed, and this effect could be serially passaged to further cultures. The C.P.E. was not observed when ether-treated extracts of cells showing C.P.E. were used for passage or when the passage material was filtered through a 100 nm filter. Appearance of C.P.E. was delayed in cultures inoculated with 220 nm filtrates of inoculum was passed through filters of greater pore size. No C.P.E. was observed after culture of bone-marrow aspirated from each of 7 patients under clinical investigation for disorders other than M.S.


Subject(s)
Bone Marrow/microbiology , Distemper Virus, Canine/isolation & purification , Multiple Sclerosis/microbiology , Adult , Animals , Bone Marrow/pathology , Cell Count , Cells, Cultured , Cytopathogenic Effect, Viral , Cytoplasm/ultrastructure , Dogs , Female , Humans , Male , Microscopy, Electron , Mononuclear Phagocyte System/pathology , Multiple Sclerosis/pathology , Neutralization Tests , Plasma Cells/pathology , Rabbits , Reticulocytes/pathology , Swine
19.
Lancet ; 2(7989): 761-5, 1976 Oct 09.
Article in English | MEDLINE | ID: mdl-61441

ABSTRACT

Mice were inoculated with human sarcoid tissue homogenates or with a first or a second passage homogenate of mouse tissue (including 0.2 mum membrane filtrates) originating from the inoculation of human sarcoid, Crohn's disease, or control tissue homogenates. Epithelioid and giant cell granulomas were present in the footpads and/or viscera of some of the mice given homogenates originating from each sarcoid or Crohn's disease tissue 15 months after inoculation but were not present in mice given control homogenates. Among mice given homogenates originating from human sarcoidosis, granulomas were present in many organs and tissues; in contrast, a pattern of selective dissemination of visceral granulomas was found among mice given homogenates originating from Crohn's disease. This differential distribution of visceral granulomas also followed the inoculation of 0.2 mum membrane filtrates. Granulomatous responses at Kveim test sites in the ear 9-17 months after inoculation of homogenatesoriginating from human sarcoidosis or Crohn's disease were confined to mice showing granulomas in footpads of viscera. The ability of the transmissible agents to induce granulomas in mice was destroyed when sarcoid or Crohn's tissues were autoclaved or when sarcoid homogenates were stored at -20degreesC for 1 week or exposed to 60Co irradiation (2.5 MR).


Subject(s)
Crohn Disease/microbiology , Sarcoidosis/microbiology , Animals , Crohn Disease/etiology , Ear , Female , Granuloma/etiology , Granuloma/pathology , Guinea Pigs , Hindlimb , Humans , Kveim Test , Lung Diseases/etiology , Lung Diseases/pathology , Mice , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/pathogenicity , Refrigeration , Sarcoidosis/etiology , Splenic Diseases/etiology , Splenic Diseases/pathology , Time Factors , Tissue Extracts , Viruses/isolation & purification
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