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Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of west Africa.

Serological evidence is presented here suggesting that a virus closely related to simian T-lymphotropic virus type III (STLV-III) infects man in Senegal, west Africa, a region where AIDS or AIDS-related diseases have not yet been observed. 25 sera from Senegalese individuals that were positive for antibodies to HTLV-III by enzyme-linked immunosorbent assay were examined for antibodies to HTLV-III and STLV-III by western blotting. Sera from individuals originating from regions where AIDS has been reported, such as the United States and Burundi (central Africa), reacted best with antigens of HTLV-III, although antibodies that cross-reacted with STLV-III p24 were also detected. Conversely, sera originating from Senegalese people reacted better with STLV-III than with HTLV-III. This was exemplified by the absence of reactivity in sera from both monkeys and Senegalese people to p41, an antigen regularly detected by sera from antibody positive individuals originating from central Africa or from the United States. In contrast sera from central Africa or the United States did not react with p32, the putative envelope transmembrane protein of STLV-III that is regularly detected by sera from both monkeys and antibody-positive Senegalese people. These results suggest that certain healthy Senegalese people have been exposed to a virus that is more closely related to STLV-III than to HTLV-III. The existence and study of such virus variants potentially with differential pathogenicity may provide important information for the development of an AIDS virus vaccine.

Africa, Western↗

Immunologic abnormality in a group of Macaca arctoides with high mortality due to atypical mycobacterial and other disease processes.

Of 54 Macaca arctoides, 44 died during the 2.5 years after their assignment to a common cage. Although early deaths were due to trauma, acute gastric dilatation, and shigellosis; latter deaths were the result of a variety of uncommon diseases including atypical mycobacterial disease, malignant lymphoma, protozoan encephalomyelitis, and other necrotizing and inflammatory lesions. Atypical mycobacterial disease due to Mycobacterium avium intracellular serotypes was the most frequent single disease agent recognized (33% [18 macaques]). This disease began in the ileum and large intestine with subsequent systemic involvement. An abnormality of host response to infective agents, in general, was indicated by the unusually high occurrence of this disease, as well as other disease processes. Morphologic evaluation of lymphoid organs revealed decreased cellularity of follicles and decreased numbers of plasma cells in all macaques, whereas T cell-dependent areas varied from hypocellular to hypercellular with 5 macaques with malignant lymphoma. The spontaneous erythrocyte rosette-forming subpopulation of T cells was decreased in peripheral blood, but was increased in lymph nodes containing atypical mycobacterial lesions. Serum immunoglobulin value decreased progressively in diseased macaques. A basic abnormality of T-cell subpopulations controlling other components of host response was suspected. Macrophages from lesions that contain mycobacterial organisms did not phagocytize latex beads normally in vitro, whereas monocytes in the blood of the same macaques were capable of in vitro phagocytosis.

Animals↗

Ultrastructural and histochemical mesangial alterations in Callitrichid IgM nephropathy (primates: platyrrhina).

The ultrastructural and histochemical alterations during different stages of spontaneously occurring IgM nephropathy in Callitrichidae were determined. Callitrichid IgM nephropathy was classified according to the light microscopic sequence of the mesangial lesions in the individual glomeruli. In minimal disease and axial proliferation mesangial cells and mesangial matrix were symmetrically increased, whereas in panmesangial disease matrix deposition exceeded the cellular responses. However, ultrastructural matrix changes such as deposition of electron-dense particles, dilatation of the matrix channel system, and slightly increased collagen fiber expression were present also in minimal disease and axial proliferation. Histochemically collagen I and III phenotypes could only be verified in glomerular sclerosis, at that time accompanied by diminution of collagen IV. The mesangial cellular lesions, in contrast, were very limited. The numerical increase in mesangial cells was associated with increased bleb formation and increased heterolysosome contents, whereas the amount of microfilaments was never increased.

Animals↗

IgM-mesangial nephropathy in callithricids.

Spontaneous IgM-mediated mesangioproliferative nephropathy was detected in 91% of tamarins and marmosets over 6 months old. The disease remains silent for long periods but is progressive. It is responsible for, or is at least related to, the cause of death in 20% of animals. Morphological characteristics are those of mesangial hyperplasia accompanied by subacute to chronic interstitial inflammation. The immunopathological demonstration of early accumulation of IgM within the mesangial cells and matrix, followed by interstitial deposition of C3, suggests that the lesion is mediated by immunological mechanisms.

Animals↗

GDNF: a novel factor with therapeutic potential for neurodegenerative disorders.

The identification of novel factors that promote neuronal survival could have profound effects on developing new therapeutics for neurodegenerative disorders. Glial cell line-derived neurotrophic factor (GDNF) is a novel protein purified and cloned based on its marked ability to promote dopaminergic neuronal function. GDNF, now known to be the first identified member of a family of factors, signals through the previously known receptor tyrosine kinase, Ret. Unlike most ligands for receptor tyrosine kinases, GDNF does not bind and activate Ret directly, but requires the presence of GPI-linked coreceptors. There are several coreceptors with differing affinities for the GDNF family members. The profile of coreceptors in a cell may determine which factor preferentially activates Ret. In vivo differences in localization of the GDNF family members, its coreceptors and Ret suggest this ligand/receptor interaction has extensive and multiple functions in the CNS as well as in peripheral tissues. GDNF promotes survival of several neuronal populations both in vitro and in vivo. Dopaminergic neuronal survival and function are preserved by GDNF in vivo when challenged by the toxins MPTP and 6-hydroxydopamine. Furthermore, GDNF improves the symptoms of pharmacologically induced Parkinson's disease in monkeys. Several motor neuron populations isolated in vitro are also rescued by GDNF. In vivo, GDNF protects these neurons from programmed cell death associated with development and death induced by neuronal transection. These experiments suggest that GDNF may provide significant therapeutic opportunities in several neurodegenerative disorders.

Animals↗

Simian T cell leukemia virus type I-induced malignant adult T cell leukemia-like disease in a naturally infected African green monkey: implication of CD8+ T cell leukemia.

Spontaneous T cell leukemia was found in an African green monkey (Cercopithecus aethiops, AGM) naturally infected with simian T cell leukemia virus type I (STLV-I). The hematological features and the evidence for monoclonal integration of provirus DNA in the leukemic cells revealed that the leukemia was an ATL-like disease. The expression of surface markers on the leukemic cells indicated that they were defined as an activated CD8+ T cell subset. Together with the finding that seven in vitro spontaneously STLV-I-transformed cell lines were CD4-CD8+, it is likely that CD8+ T cells are transformed by STLV-I in AGMs, in contrast with human ATL. Finally, we assessed characteristics of the CD8 chains on these transformed cells. The result indicated that the leukemic cells expressed only the alpha chains but not the beta chains. However, in the case of in vitro-transformed cell lines the expression pattern of the CD8 chains varied in individual monkeys. Thus, STLV-I may preferentially transform CD8+ (both alphaalpha+ and alphabeta+) T cells in AGMs.

Adult↗

Detection of herpesvirus DNA in cottontop tamarins: no association with colitis.

Colitis occurs spontaneously in the cottontop tamarin; it shares similar clinical, endoscopic and histological features with, and has a similar response to treatment as, human ulcerative colitis. An association between human ulcerative colitis and the presence of DNA from multiple herpesviruses (human herpesvirus 6 (HHV-6), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the colon has been described. Intestinal herpesvirus infection may be involved in the pathogenesis of this condition. In a pilot study, coded full thickness colonic specimens from 27 cottontop tamarins were examined for the presence of HHV-6, CMV and EBV DNA using the nested polymerase chain reaction. The sections represented a spectrum of disease activity ranging from histologically normal bowel to severe colitis. A low prevalence of DNA from these viruses was found, which bore no relation to the presence of inflammation. Although these herpesviruses may have a pathogenetic role in human ulcerative colitis, they are not associated with colitis in this animal model.

Animals↗

Treatment of ulcerative colitis in the cottontop tamarin using antibody to tumour necrosis factor alpha.

BACKGROUND: The aetiology and pathophysiology of ulcerative colitis remains unclear; however, there is increasing recognition of the critical role of inflammatory cytokines in the pathogenesis of this disease. Among these, tumour necrosis factor alpha (TNF alpha) seems to play an important role. AIM: To study the effects of an engineered human monoclonal antibody to TNF alpha (CDP571) in the treatment of idiopathic ulcerative colitis in the cottontop tamarin. METHODS: Six cottontop tamarins with confirmed ulcerative colitis received repeated doses of CDP571. Progression of disease was assessed by measuring both body weight and rectal biopsy pathology. RESULTS: All animals showed a rapid improvement in clinical condition and rectal biopsy pathology that was maintained following completion of the therapy. CONCLUSION: These studies indicate the efficacy of selective antibody therapy to TNF alpha for the treatment of ulcerative colitis in a primate and suggest that similar therapy in human could be of value.

Animals↗

Callitrichid IgM-nephropathy--an old age-related disease?

In 185 callitrichids of exactly known age the occurrence of mesangial IgM-deposits and mesangial lesions has been evaluated. Mesangial IgM-deposits were observed already in early infancy, at that time without morphological sequelae. Signs of mesangial lesions were first observed in a 3-months old animal and with a sharp increase of mesangial lesions between 4 months and one year of age all suggesting an onset early in life. In contrast in higher age groups a significant number of animals suffered from glomerulosclerosis without IgM deposits, which could be interpreted as 'old age nephropathy' independent from IgM-nephropathy.

Aging↗

The pathoparasitology of the alimentary tract and pancreas of nonhuman primates: a review.

A review of the literature concerning the gross and histologic lesions associated with protozoal and metazoal parasitism in the alimentary tract and pancreas of nonhuman primates is presented. In addition, the natural history, morphology, life cycle, methods for diagnosis, and potential for zoonotic disease are reviewed briefly for each parasite discussed. The parasite species reviewed in detail are those most common or most likely to produce lesions in the alimentary tract and pancreas of the nonhuman primate host. All parasites, both pathogenic and nonpathogenic, in each major group (protozoa: flagellates, sarcodines, sporozoans, neosporans, and ciliates; and metazoa: trematodes, cestodes, nematodes, acanthocephalans, and pentastomids) that have been reported in the nonhuman primate alimentary tract and pancreas are presented in tables.

Acanthocephala↗

Disseminated encephalitozoonosis in captive, juvenile, cotton-top (Saguinus oedipus) and neonatal emperor (Saguinus imperator) tamarins in North America.

Disseminated encephalitozoonosis was diagnosed in 2 sibling, juvenile, cotton-top tamarins (Saguinus oedipus) and 3 sibling, neonatal, emperor tamarins (S. imperator) by use of histologic examination, histochemical analysis, electron microscopy, and polymerase chain reaction (PCR) analysis with nucleotide sequencing. All tamarins were captive born at zoos in North America and died with no premonitory signs of disease. The main pathologic findings were myocarditis (4/5), hepatitis (3/5), interstitial pneumonia (3/5), skeletal myositis (3/5), meningoencephalitis (2/5), adrenalitis (2/5), tubulointerstitial nephritis (1/5), myelitis (1/5), sympathetic ganglioneuritis (1/5), and retinitis (1/5). Central nervous system lesions were the most prominent findings in cotton-top tamarins. The inflammation was predominantly lymphocytic and suppurative in cotton-top tamarins, whereas emperor tamarins had granulomatous or lymphoplasmacytic lesions. Intralesional periodic acid-Schiff-, gram-, or acid-fast (or all 3)-positive, oval-to-elliptical shaped organisms were found in 1 cotton-top and the 3 emperor tamarins. By electron microscopy, these organisms were consistent with microsporidia of the genus Encephalitozoon. E. cuniculi genotype III was detected by PCR analysis and sequencing in paraffin-embedded brain, lung, and bone marrow specimens from the cotton-top tamarins. Although PCR results were negative for one of the emperor tamarins, their dam was seropositive for E. cuniculi by ELISA and Western blot immunodetection. These findings and recent reports of encephalitozoonosis in tamarins in Europe suggest that E. cuniculi infection may be an emerging disease in callitrichids, causing high neonatal and juvenile mortality in some colonies. The death of 2 less than 1-day-old emperor tamarins from a seropositive dam supports the likelihood of vertical transmission in some of the cases reported here.

Adrenal Glands↗

Detection of Ebola viral antigen by enzyme-linked immunosorbent assay using a novel monoclonal antibody to nucleoprotein.

With the increase in international traffic, the risk of introducing rare but severe infectious diseases like Ebola hemorrhagic fever is increasing all over the world. However, the system for the diagnosis of Ebola virus infection is available in a limited number of countries. In the present study, we developed an Ebola virus antigen-detection enzyme-linked immunosorbent assay (ELISA) system using a novel monoclonal antibody (MAb) to the nucleoprotein (NP). This antibody recognized an epitope defined by a 26-amino-acid stretch near the C terminus of NP. In a sandwich ELISA system with the MAb, as little as 30 ng of purified recombinant NP (rNP) was detected. Although this MAb was prepared by immunization with rNP of subtype Zaire, it also reacted to the corresponding region of NP derived from the Reston and Sudan subtypes. These results suggest that our ELISA system should work with three of four Ebola subtypes. Furthermore, our ELISA system detected the NP in subtype Reston-infected monkey specimens, while the background level in noninfected specimens was very low, suggesting the usefulness of the ELISA for laboratory diagnosis with clinical specimens.

Animals↗

Studies with the baboon endogenous virus and its pseudotype of murine sarcoma virus in marmosets.

Three marmoset species (Saguinus oedipus oedipus, S. fuscicollis, Callithrix jacchus) failed to show evidence of infection or disease following inoculation of baboon endogenous type-C virus (BaEV). Cells infected with a Kirsten murine sarcoma-BaEV pseudotype (MSV[BaEV]) produced a progressive fibrosarcoma in S. o. oedipus and tumors in S. fuscicollis and C. jacchus which regressed. Tumor formation is believed to be due to growth of inoculated, virus-infected cells and not transformation of marmoset cells. S. o. oedipus showed the best serum neutralizing antibody response to BaEV and MSV(BaEV), S. fuscicollis a moderate response and C. jacchus no response.

Animals↗

Rhesus rhadinovirus infection in healthy and SIV-infected macaques at Tulane National Primate Research Center.

Rhesus rhadinovirus (RRV) infection was quantified in peripheral blood mononuclear cells (PBMC) from healthy and simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) at the Tulane National Primate Research Center and in a large collection of simian acquired immunodeficiency syndrome--(SAIDS)-associated lymphomas. Quantification of RRV load was performed by real-time PCR using amplification primers specific for the RRV interleukin-6 homologue (RRV vIL-6). RRV infection was detected infrequently and at low levels in PBMC of randomly selected healthy animals. Examination of longitudinally collected PBMC from 22 SIV-infected animals throughout progression to SAIDS revealed similarly low RRV loads that sometimes increased with advancing disease. RRV infection was detected more frequently in the peripheral blood of SIV-infected animals than in healthy animals. Examination of SAIDS-associated lymphomas showed that RRV is rare within the tumor mass, likely representing infection in an occasional tumor-infiltrating cell or contaminating blood. The results indicate that RRV infection in PBMC is not predictive of, and is apparently not required for, development of lymphoma or hyperplastic lymphadenopathy in SIV-infected animals at TNPRC.

Animals↗

Ampullary carcinoma in a group of aged rhesus macaques (Macaca mulatta).

Ampullary carcinoma was diagnosed in 6 rhesus macaques that ranged in age from 20 to 35 years. Signalment, premonitory signs of disease, and results of clinical biochemical and hematologic analyses varied among animals. Histologically, the neoplastic cells obliterated the ampulla, with regional spread to the duodenum in all 6 animals and to the pancreas in one animal. Two animals had metastases to the lung, and another two had metastases to the pancreoduodenal lymph nodes and liver. One animal had mesocolonic metastasis. Malignant tumors of the ampullary region are rare in domestic animals, and account for less than 5% of all cancers of the digestive tract in humans.

Aging↗

Junin virus infection of Callithrix jacchus: pathologic features.

Infection of Callithrix jacchus, a New World primate, with the prototype strain of Junin virus produced a severe disease. The animals developed multifocal hemorrhages and characteristic microscopic lesions such as meningoencephalitis, interstitial pneumonia, lymphocytic depletion of lymphatic tissue, hepatocytic necrosis, and a variable decrease in bone marrow cellularity. High virus concentrations correlated with lesions, and with the presence of viral antigenic determinants as revealed by immunofluorescent methods. With the exception of central nervous system damage, the morphological features and immunohistochemical and viral findings were similar to those recorded in human Argentine hemorrhagic fever.

Animals↗

Consequences of nigrostriatal denervation on the gamma-aminobutyric acidic neurons of substantia nigra pars reticulata and superior colliculus in parkinsonian syndromes.

To examine the effects of nigrostriatal denervation on the substantia nigra pars reticulata (SNpr), one of the main outputs of the basal ganglia, we used quantitative in situ hybridization to analyze the messenger RNA coding for Mr 67,000 glutamic acid decarboxylase (GAD67 mRNA) in the SNpr neurons from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP), and their respective controls. In MPTP-intoxicated monkeys, the expression of GAD67 mRNA was increased in the SNpr neurons, and the increase was reversed by L-dopa treatment. There were no differences in the level of GAD67 mRNA between PD patients who had been treated with L-dopa and control subjects. Combined with the previously reported increased expression of GAD67 mRNA in the internal segment of the pallidum of MPTP-intoxicated monkeys, these data suggest that the gamma-aminobutyric acid (GABAergic) activity of the output system of the basal ganglia is globally increased by nigrostriatal denervation. We also analyzed the level of GAD67 mRNA expression in the superior colliculus, a structure that receives the inhibitory influence of the GABAergic neurons of the SNpr and that is involved in eye movement control. GAD67 mRNA expression was reduced in both MPTP-intoxicated monkeys, whether or not they received L-dopa therapy, and PD patients, compared to their respective controls. This decrease may result from the hyperactivity of the inhibitory nigrotectal pathway, but also from other influences since it was not corrected by L-dopa therapy. These changes may account for the slight ocular motor and visuospatial cognitive impairment occurring in PD, even after L-dopa therapy.

Animals↗