RESUMEN
Contemporary data and concepts about the role of symbiogenesis in organization, functioning, and evolution of biosystems at different organizational levels allow to contemplate the forming of a symbiotic approach to solving theoretical and practical problems in biology. According to the author's concept, at the organismic level, the basic unit should be considered as not being an individual, but autocenosis, i.e., a self-regulating system of "host-symbionts" type. Then, democenosis, being a system of autocenoses, would correspond to the population level, and speciocenosis, being a system of democenoses, would correspond to the species level. Within democenoses, not individuals, but autocenoses are subject to natural selection. Different links in trophic chains and webs are not "individuals" or "populations" but auto- and democenoses. However, symbiotic approach does not leave out the population paradigm and should develop in parallel with it. Novel concepts in the field of symbiology are indicative of this point of view.
Asunto(s)
Modelos Biológicos , Simbiosis/fisiología , AnimalesRESUMEN
IFN-gamma is a cytokine with pleiotropic functions that participates in immune and autoimmune responses. The lack of IFN-gamma is known to delay the development of autoimmune diabetes in nonobese diabetic (NOD) mice. Splenocytes from diabetic NOD and IFN-gamma knockout (KO) NOD mice transfer diabetes into NOD recipients equally well. However, adoptive transfer of diabetogenic T cells from NOD mice into NOD.IFN-gamma-KO or NOD mice lacking beta-chain of IFN-gamma receptor (NOD.IFN-gammaRbeta-KO) appeared to be much less efficient. We found that IFN-gamma influences the ability of diabetogenic cells to penetrate pancreatic islets. Tracing in vivo of insulin-specific CD8+ T cells has shown that homing of these cells to the islets of Langerhans was affected by the lack of IFN-gamma. While adhesion of insulin-specific CD8+ cells to microvasculature was normal, the diapedesis was significantly impaired. This effect was reversible by treatment of the animals with rIFN-gamma. Thus, IFN-gamma may, among other effects, influence immune and autoimmune responses by supporting the homing of activated T cells.
Asunto(s)
Movimiento Celular/inmunología , Diabetes Mellitus Tipo 1/inmunología , Interferón gamma/fisiología , Islotes Pancreáticos/inmunología , Subgrupos de Linfocitos T/inmunología , Traslado Adoptivo , Animales , Presentación de Antígeno/genética , Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/patología , Femenino , Inyecciones Intravenosas , Interferón gamma/biosíntesis , Interferón gamma/deficiencia , Interferón gamma/genética , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Transfusión de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Bazo/patología , Bazo/trasplante , Subgrupos de Linfocitos T/patologíaRESUMEN
Genetic analysis of autoimmune insulin-dependent diabetes mellitus (IDDM) has focused on genes controlling immune functions, with little investigation of innate susceptibility determinants expressed at the level of target beta cells. The Alloxan (AL) Resistant (R) Leiter (Lt) mouse strain, closely related to the IDDM-prone nonobese diabetic (NOD)/Lt strain, demonstrates the importance of such determinants. ALR mice are unusual in their high constitutive expression of molecules associated with dissipation of free-radical stress systemically and at the beta-cell level. ALR islets were found to be remarkably resistant to two different combinations of beta-cytotoxic cytokines (IL-1beta, tumor necrosis factor alpha, and IFN-gamma) that destroyed islets from the related NOD and alloxan-susceptible strains. The close MHC relatedness between the NOD and ALR strains (H2-Kd and H2-Ag7 identical) allowed us to examine whether ALR islet cells could survive autoimmune destruction by NOD-derived Kd-restricted diabetogenic cytotoxic T lymphocyte clones (AI4 and the insulin-reactive G9C8 clones). Both clones killed islet cells from all Kd-expressing strains except ALR. ALR resistance to diabetogenic immune systems was determined in vivo by means of adoptive transfer of the G9C8 clone or by chimerizing lethally irradiated ALR or reciprocal (ALR x NOD)F1 recipients with NOD bone marrow. In all in vivo systems, ALR and F1 female recipients of NOD marrow remained IDDM free; in contrast, all of the NOD recipients became diabetic. In conclusion, the ALR mouse presents a unique opportunity to identify dominant IDDM resistance determinants expressed at the beta cell level.
Asunto(s)
Autoinmunidad/inmunología , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/inmunología , Predisposición Genética a la Enfermedad , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/patología , Traslado Adoptivo , Aloxano/farmacología , Animales , Autoinmunidad/genética , Trasplante de Médula Ósea/inmunología , Muerte Celular/efectos de los fármacos , Quimera/genética , Quimera/inmunología , Células Clonales/inmunología , Células Clonales/metabolismo , Ciclofosfamida/farmacología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patología , Femenino , Antígenos de Histocompatibilidad Clase I/análisis , Antígenos de Histocompatibilidad Clase I/inmunología , Insulina/metabolismo , Secreción de Insulina , Interferón gamma/biosíntesis , Interferón gamma/farmacología , Interferón gamma/toxicidad , Interleucina-1/farmacología , Interleucina-1/toxicidad , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos NOD , Ratones Endogámicos , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/toxicidadRESUMEN
Novel single exon genes Abeta4-7 comprising the Abeta6 gene family have been cloned from mouse mutants surviving transplantable metastatic tumors. Their protein coding sequences are similar to H2-Ab cDNA which encodes antigen-binding molecules of antigen presenting cells (APC); their promoters and/or signal sequences are unrelated to Ab sequences but found in other eukaryotic genes. Abeta4(b) protein was demonstrated on macrophages and B cells that are APC. The Abeta6(w302) appears to be an ancient gene ancestral to major histocompatibility complex (MHC) class II beta genes. However, unlike the MHC class II, the Abeta4-7 genes are not involved in skin graft rejection. Despite inbreeding, the Abeta6(w302) locus remains unfixed in several strains of mice. The number of Abeta genes and their alleles varied between individual mice; they do not map into the H2 region but appear to be scattered over the genome. The Abeta6 gene family is molecularly unstable in Abeta6(w302)-positive (but not in Abeta6(w302)-negative) mice which are somatic mosaics for these genes. Biological features of Abeta4-7 genes make them remarkably different from the classical MHC gene system. All available evidence strongly suggests that these genes control susceptibility/resistance to the spread of metastatic tumors.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/genética , Metástasis de la Neoplasia/inmunología , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/mortalidad , Animales , Células Presentadoras de Antígenos , Secuencia de Bases , Segregación Cromosómica , Clonación Molecular , Exones , Variación Genética , Heterocigoto , Prueba de Histocompatibilidad , Intrones , Proteínas de la Membrana , Ratones , Ratones Endogámicos , Ratones Mutantes , Modelos Genéticos , Datos de Secuencia Molecular , Mosaicismo , SobrevivientesRESUMEN
Metastatic tumors escape from immune response and spread in the body; survivors are very rare. Novel single exon genes A beta 4-7 and a pseudogene A beta 8 psi have been cloned from survivors. Their protein coding sequences are similar to MHC class II beta H2-Ab cDNA while their promoter is different from MHC promoters. The A beta 4 protein was demonstrated on macrophages (antigen presenting cells). The A beta gene family is genetically unstable in germ line and somatic cells of survivors. Mutants S-27 and S-87/1 lost the A beta 5s5 and acquired the A beta 6w302 gene; the Ab gene mutated in S-27. The proposed mechanism of resistance is molecular instability of the A beta gene family resulting in somatic mutations and wandering immune responses that destroy the tumor in the survivor.
Asunto(s)
Linfoma/genética , Mutación , Neoplasias Inducidas por Radiación/genética , Animales , Antígenos H-2/genética , Inmunidad Innata , Linfoma/etiología , Ratones , Ratones Mutantes , Metástasis de la NeoplasiaRESUMEN
Vascular endothelial growth/permeability factor (VEG/PF) is expressed in some normal tissues and at high levels in a wide range of tumors. This growth factor is believed to be a key mediator of angiogenesis. Recent reports have shown that VEG/PF mRNA in the normal rat uterus is stimulated by estradiol (E2). In this study, we investigated the expression of VEG/PF in the mammary gland and 7,12-dimethylbenz(a)anthracene (DMBA)-induced, hormone-dependent mammary tumor of the rat model, and also whether VEG/PF is regulated by E2. VEG/PF mRNA from tumor extracts was amplified by RT-PCR with VEG/PF primers and generated two main products which corresponded in size to those expected for VEG/PF 164 and 120. In some cases, a third product corresponding in size to that expected for VEG/PF 188 was also generated. No such PCR products were generated from equal amount of RNA from normal mammary tissue, rat brain, or liver. Using immunocytochemistry, VEG/PF expression was detected in the epithelial cells of the tumors. We developed an ELISA assay to measure VEG/PF protein concentrations and found a 4-fold difference between normal mammary glands (1.3 +/- 0.11 ng/mg protein) and tumors (4.44 +/- 0.66) (P < 0.01). E2 treatment (5 microg/rat, s.c.) of rats 24 h after ovariectomy, greatly enhanced the expression of RT-PCR products in tumors within 2 h, which reached a maximum at 6-8 h but declined by 48 h. VEG/PF concentrations were also increased 8-12 h after E2 injection. When rats were given two injections of aromatase inhibitor 4-hydroxyandrostenedione (4-OHA 10 mg/rat s.c.) 24 h apart, to reduce estrogen concentrations, a low level of RT-PCR products was maintained for at least 96 h. After a single injection of 4-OHA, RT-PCR products remained low until 36 h when an increase occurred corresponding with a rise in plasma E2 levels. Injection of E2 2 h after 4-OHA treatment, caused a rise in RT-PCR products in 6-8 h. However, there was no significant change in VEG/PF concentrations. An increase in VEG/PF protein concentrations followed the increase in mRNA levels by 4-6 h. Thus, it appears that E2 causes a rapid induction of VEG/PF expression in mammary tumors that is similar to that observed in the normal uterus. These findings suggest that one mechanism by which estrogen acts as a mammary tumor promotor is by stimulating VEG/PF, leading to increased tumor angiogenesis and/or permeability of the microvessels to allow tumor cell migration.
Asunto(s)
Factores de Crecimiento Endotelial/metabolismo , Estradiol/farmacología , Linfocinas/metabolismo , Neoplasias Mamarias Animales/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Androstenodiona/análogos & derivados , Androstenodiona/farmacología , Animales , Factores de Crecimiento Endotelial/genética , Inhibidores Enzimáticos/farmacología , Femenino , Inmunohistoquímica , Linfocinas/genética , Glándulas Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/inducido químicamente , Ovariectomía , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The expression of aromatase by breast cancer cells and the role of locally produced estrogen in the stimulation of tumor growth has been controversial. The present study was performed to determine the site of aromatization in human breast cancers, using both immunocytochemistry and in situ hybridization. The functional significance of locally produced estrogens on growth of the tumor was addressed by measuring aromatase activity and a marker of proliferation (PCNA score). In addition, histocultures of some tumors were carried out to investigate whether testosterone aromatization could stimulate tumor proliferation. Of the 19 tumors investigated, 10 (52.6%) showed significant immunoreactivity to antiaromatase antibody in the cytoplasm of tumor epithelial cells and in surrounding stromal cells. The presence of aromatase mRNA detected by ISH was also located in tumor epithelial cells and stromal cell, and the pattern of expression was the same as with immunocytochemistry. In the ten tumors that showed immunoreaction to aromatase, the average aromatase activity measured in cryosections was 286.5 +/- 18.6 (SE) fmol estrogen/mg protein.h, whereas in nine tumors with weak aromatase immunoreaction, the enzyme activity was 154.7 +/- 19.3 (SE) fmol estrogen/mg protein-h (P < 0.05). The mean PCNA score was 33.8 +/- 5.1 (SE)% in strongly stained tumors and 20.8 +/- 2.0 (SE)% in weakly stained tumors (P < 0.05). Aromatase activity level and PCNA score were significantly correlated. In histoculture of four tumors, estradiol increased the incorporation of [3H]-thymidine into DNA. In two of these tumors, aromatase activity was high and [3H]-thymidine incorporation into DNA was also stimulated by testosterone. In the other two tumors that had low aromatase activity, no such stimulation occurred with testosterone. The results indicate that aromatase is expressed mainly in tumor epithelial cells and that sufficient amounts of estrogen are synthesized by the tumor to produce a proliferative response. It is concluded that estrogen synthesis by cancer cells could play a important role in promoting growth in a significant proportion of breast tumors.
Asunto(s)
Aromatasa/biosíntesis , Neoplasias de la Mama/enzimología , Regulación Enzimológica de la Expresión Génica , Biosíntesis de Proteínas , ARN Mensajero/biosíntesis , Transcripción Genética , Secuencia de Bases , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/enzimología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/enzimología , Carcinoma Lobular/patología , Cartilla de ADN , Sondas de ADN , Epitelio/enzimología , Epitelio/patología , Estradiol/biosíntesis , Estrona/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Posmenopausia , Premenopausia , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisisRESUMEN
The effects of aromatase inhibitors 4-hydroxyandrostenedione (4-OHA), CGS 16949A, and CGS 20267, and of the antiestrogen tamoxifen (TAM), were studied on the growth of human breast carcinoma in a nude mouse model. To simulate the postmenopausal breast cancer patient, tumors were formed from inoculates of MCF-7 cells transfected with the human aromatase gene to provide a source of non-ovarian estrogen in ovariectomized mice. Tumor growth was significantly inhibited by all treatments (P < 0.05). Greater reduction in growth occurred in mice treated with TAM combined with aromatase inhibitors than with TAM alone. Tumor progesterone receptor concentrations were unaltered by TAM treatment but were reduced by aromatase inhibitors. Progesterone receptor concentrations correlated with tumor growth. The greatest reduction occurred in tumors of CGS 20267-treated mice in which no progesterone receptors were detected. In the ovariectomized mice used in these studies, uterine weight was maintained by estrogen produced from the tumor. Uterine weight was reduced by aromatase inhibitors but not by TAM treatment. However, there was a significant increase in uterine weight in mice treated with the combination of TAM and 4-OHA. Thus, the agonist effect of TAM was evident when estrogen synthesis was inhibited. The results indicate that aromatase inhibitors have potent effects on mammary tumor growth but lack the estrogenic effects on the uterus observed with TAM. There appeared to be no significant benefit in combining TAM with 4-OHA over 4-OHA treatment alone.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de la Aromatasa , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/enzimología , Androstenodiona/análogos & derivados , Androstenodiona/farmacología , Animales , División Celular/efectos de los fármacos , Fadrozol/farmacología , Femenino , Letrozol , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nitrilos/farmacología , Tamaño de los Órganos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tamoxifeno/farmacología , Triazoles/farmacología , Útero/anatomía & histología , Útero/efectos de los fármacosRESUMEN
The kinetics of [3H]-L-glutamate binding to brain synaptic membranes (SM) and to glutamate-binding proteins (GBP) was determined with agonist and monoclonal antibodies (MAbs). It was revealed, that rat and human brain GBP have individual protein components with M(r) from 14 to 92 kDa. Quisqualate inhibited [3H]-L-glutamate binding to solubilized and to purified 68 kDa protein component. MAbs have the most activity, and NMDA was failure. It has been shown that 68 kDa component antigen determinants are similar to those of bovine, frog and rat brain synaptic membranes. Anti-GBP monoclonal antibodies blocked functional non-NMDA receptors in isolated frog spinal cord. Immunocytochemistry was done on rat and human brain sections. Distribution of quisqualate receptors was determined with light and electron microscopy. Some properties of vertebrate CNS non-NMDA receptors are discussed.
Asunto(s)
Encéfalo/efectos de los fármacos , Ácido Quiscuálico/metabolismo , Receptores de Glutamato/efectos de los fármacos , Adulto , Animales , Anticuerpos Monoclonales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Glutamatos/inmunología , Glutamatos/metabolismo , Humanos , Inmunohistoquímica , Ligandos , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Microscopía Inmunoelectrónica , Unión Proteica/efectos de los fármacos , Rana ridibunda , Ratas , Receptores AMPA , Receptores de Glutamato/metabolismo , Receptores de Glutamato/ultraestructuraRESUMEN
As many as 97 patients with myocardial lesions: congestive and hypertrophic cardiomyopathy (CMP), postmyocarditis CMP (PM CMP), myocarditis (MC), alcoholic heart injury (AHI), coronary heart disease (CHD), vegetodysovarian myocardiodystrophy were examined by means of a complex of the virological tests (for Coxsackie B, Epstein-Barr and hepatitis B viruses) and immunoassays (for antibodies to different components of the myocardium, leukocyte migration inhibition test, antibody-dependent cellular cytotoxicity test, measurements of T and B lymphocytes and their subpopulations, and so forth). Virus infection was shown to be of a role for the onset of acute MC (usually reversible) and congestive CMP. At the same time the autoimmune mechanisms of the lesions were conclusively ascertained in MC associated with heart failure and in PM CMP. In patients with congestive CMP and AHI coupled with heart failure, antibodies to nerve fibers of the myocardium could be demonstrated in the presence of T-lymphocyte deficiency and high titers of antibodies to Epstein-Barr virus. This does not allow excluding myocardial denervation leading to refractory heart failure. Some immunological parameters made use of in the study provide an opportunity of an objective evaluation of the effect glucocorticoid treatment produces on patients suffering from MC and PM CMP.
Asunto(s)
Cardiomiopatías/diagnóstico , Miocarditis/diagnóstico , Virosis/diagnóstico , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Cardiomiopatías/etiología , Cardiomiopatías/inmunología , Cardiomiopatía Alcohólica/diagnóstico , Cardiomiopatía Alcohólica/etiología , Cardiomiopatía Alcohólica/inmunología , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/etiología , Cardiomiopatía Hipertrófica/inmunología , Femenino , Humanos , Inmunidad Celular , Masculino , Miocarditis/etiología , Miocarditis/inmunología , Virosis/complicaciones , Virosis/inmunologíaRESUMEN
Altogether 15 untreated patients aged 16 to 55 with diffuse toxic goiter had morphologically confirmed diagnosis of the presence of antibodies to Coxsackie virus (group B); titers of group A (1:128 and more) were revealed in 3 of them. It indicated recent (not more than 2 yrs.) Coxsackie virus infection. Such titers were absent in the control group (18 healthy persons). Difference in the study and control groups was statistically significant (p less than 0.05). The role of Coxsackie virus in the breakdown of natural tolerance to autologous thyroid tissue was discussed.
Asunto(s)
Infecciones por Coxsackievirus/complicaciones , Enfermedad de Graves/etiología , Adolescente , Adulto , Anticuerpos Antivirales/análisis , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Infecciones por Coxsackievirus/inmunología , Enterovirus Humano B/inmunología , Femenino , Enfermedad de Graves/inmunología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Circulation of a virus similar to human hepatitis A virus by antigenic and some other properties was observed among African green monkeys imported from their natural habitats. In some of the monkeys this virus caused a disease similar to hepatitis A in many features.
Asunto(s)
Hepatitis A/veterinaria , Hepatitis Viral Animal/inmunología , Enfermedades de los Monos/inmunología , Animales , Chlorocebus aethiops , Heces/microbiología , Anticuerpos Antihepatitis/análisis , Hepatitis Viral Animal/microbiología , Hepatitis Viral Animal/patología , Hepatovirus/inmunología , Hepatovirus/aislamiento & purificación , Inmunoglobulina M/análisis , Hígado/microbiología , Hígado/patología , Enfermedades de los Monos/microbiología , Enfermedades de los Monos/patología , Cuarentena , Factores de TiempoRESUMEN
A model of persistent infection with Coxsackie B-3 virus was developed in adult mice with clinical manifestations of the disease and long-term (up to 13 months) excretion of the causative agent. The method of multiple organ cultures was shown to be suitable for isolation of the persisting enterovirus. The presence of persistent infection was confirmed by the detection of IgM antibody in repeated daily examinations of the animals for 4 months. It seems to be expedient to use this model for investigations of the pathogenesis and methods of treatment of persistent Coxsackie B-3 infection in experimental animals.
Asunto(s)
Infecciones por Coxsackievirus/microbiología , Modelos Animales de Enfermedad , Animales , Anticuerpos Antivirales/análisis , Enfermedad Crónica , Infecciones por Coxsackievirus/inmunología , Infecciones por Coxsackievirus/mortalidad , Enterovirus Humano B/inmunología , Enterovirus Humano B/aislamiento & purificación , Ratones , Ratones Endogámicos BALB C , Factores de TiempoRESUMEN
Opposite changes occur in the intensity of UV-fluorescence (UVF) in irradiated (0.1 Gy and 5.0 Gy) HeLa cells. The radiometric study has demonstrated that there is a correlation between the number of tryptophan-containing proteins and UVF intensity in nonirradiated and irradiated (5.0 Gy) cells during culture growth. Such a correlation was absent in cells exposed to 0.1 Gy radiation. Low radiation doses (0.1 Gy) have maximum action on cytoplasm membrane fluorescence. Low-level radiation changes the intensity of the ANS probe fluorescence connected with cell membranes, and the intensity of the cell protein UVF. High radiation doses increase and low doses decrease the probe fluorescence.
Asunto(s)
Supervivencia Celular/efectos de la radiación , Dosis de Radiación , Fluorescencia , Colorantes Fluorescentes , Células HeLa/efectos de la radiación , Humanos , Rayos UltravioletaRESUMEN
The paper presents the results of experimental infection of monkeys with virus-containing specimens from a patient with fecal-oral non-A-non-B hepatitis; the study was aimed at the determination of the possibilities of simulating this infection. Of the 8 monkeys infected with the material containing virus particles of fecal-oral non-A-non-B hepatitis 5 monkeys developed the infection manifested in virus excretion in fecal specimens, a rise in the level of serum aminotransferases, and typical histological lesions of the liver tissue. The infection could also be produced by inoculation of monkeys with virus-containing material from monkey. The above results indicate that the virus isolated from a human suffering from fecal-oral non-A-non-B hepatitis may induce in experimentally infected Macaca fascicularis monkeys a pathological process simulating viral hepatitis.
Asunto(s)
Cercopithecus , Chlorocebus aethiops , Modelos Animales de Enfermedad , Hepatitis C/transmisión , Hepatitis Viral Humana/transmisión , Macaca fascicularis , Macaca , Animales , Anticuerpos Antivirales/análisis , Biopsia con Aguja , Heces/microbiología , Hepatitis A/transmisión , Hepatitis C/microbiología , Hepatitis C/patología , Virus de Hepatitis/inmunología , Hígado/patología , Boca/microbiología , Factores de TiempoRESUMEN
A case of spontaneous hepatitis was detected in experiments aimed at working out the conditions for reproduction of the immunosuppressed state in Macaca fascicularis with the purpose of subsequent infection of these monkeys with non A non B hepatitis virus transmitted by the fecal-oral route. One of 6 monkeys at the 8th day of the experiment was found to have developed an increase in the level of serum aminotransferases which grew progressively reaching high values by day 14. Fecal specimens from this monkey collected on the 5th day and later contained spherical virus-like structures 27 nm in diameter, antigenically identical with hepatitis A (HAV) virus. In the other 5 monkeys, no similar structures were found in fecal specimens throughout the experiment. The monkey with the signs of hepatitis was sacrificed on the 16th day of experiment, i. e. on the 8th day from the onset of hyperenzymemia. Immune electron microscopy of extracts of hepatic tissue and fecal specimens collected from this monkey has revealed 27 nm particles antigenically identical with HAV. The bulk of viral particles from the liver sedimented in cesium chloride buoyant density zone of 1.32 g/cm3, and from fecal specimens in the zone of 1.36 g/cm3. In the liver of this monkey, histological changes were found which are observed in acute hepatitis, and HAV antigen in hepatocyte cytoplasm was detected by the fluorescent antibody technique. It is suggested that the spontaneous disease of this monkey was due to natural infection with HAV which could be provoked by experimental immunosuppression.
Asunto(s)
Hepatitis A/etiología , Inmunosupresores/farmacología , Macaca fascicularis/inmunología , Macaca/inmunología , Alanina Transaminasa/sangre , Animales , Anticuerpos Antivirales/análisis , Aspartato Aminotransferasas/sangre , Ciclofosfamida/administración & dosificación , Heces/microbiología , Hepatitis A/inmunología , Hepatitis A/microbiología , Hepatovirus/inmunología , Hepatovirus/aislamiento & purificación , Hidrocortisona/administración & dosificación , Hígado/microbiología , Factores de Tiempo , Virión/aislamiento & purificaciónRESUMEN
The simplified micromodification of the leukocyte adhesion inhibition (LAI) test has shown that the LAI tests both for lymphocytes and for leukocytes may be equally used as additional methods of diagnostics of the early stages of breast cancer. The detailed study of the kinetics and cellular mechanisms of the method has shown that the LAI reaction belongs to the earliest reactions of T-cellular immunity and is mediated by T-cell lymphokine. The study of sensitivity and specificity of the method revealed that the suggested micromodification of the LAI test may be used in experimental and clinical research for the study of the subpopulation of T-cells-producers of the LAI factor as well as for monitoring of the T-cell immunity in the cancer patients during treatment.