Disease in macacus monkeys inoculated with ECHO viruses.
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Gross and microscopic features closely resembling those found in Menetrier's disease in man are described in a 20-month-old rhesus monkey. The gastric lining was characterized by greatly enlarged rugae caused by mucosal hypertrophy and hyperplasia along with outfolding of the muscularis mucosa and the submucosa. The mucosa and submucosa were infiltrated with inflammatory cells, mainly lymphocytes and plasma cells.
The brains of 21 rhesus monkeys inoculated with SIVMAC251 were examined after intervals ranging from 3 to 27 months and compared with five uninoculated controls. Eighteen animals became infected and individually exhibited several distinct patterns of disease. Nine (50%) had largely intramural leptomeningeal venous infiltrates (LMVI) without multinucleate giant cells (MGC) or foamy macrophages. Three (17%) had only MGC lesions, involving the cerebral parenchyma. One had both patterns and five (33%) neither. The controls had sparse and tiny LMVI only, similar to three inoculated animals that did not become infected. Immunohistochemistry showed the predominance of T and B lymphocytes in LMVI and choroid plexus mononuclear lesions but a predominance of macrophages over lymphocytes in the MGC lesions. Specific disease patterns differed in their association with the humoral immune response. Animals with LMVI were all hypergammaglobulinaemic when killed compared to pre-inoculation levels, and the size of the change in serum immunoglobulin concentration was positively correlated with a quantitative index of LMVI density. Furthermore, their post-mortem lymph node histology was hyperplastic. In contrast, animals found at autopsy to have MGC brain lesions were hypogammaglobulinaemic compared to preinoculation. The results are consistent with two phases in SIV-associated disease: one characterized by LMVI and hypergammaglobulinaemia and another featuring MGC and hypogammaglobulinaemia.
In this study the long term effects of vasectomy on serum lipid profile, in vitro platelet aggregability and the risk of developing acute myocardial infarction have been elucidated in a monkey model. Four groups were made viz. (I) atherogenic diet fed vasectomised, (II) atherogenic diet fed control, (III) stock diet fed vasectomised and (IV) stock diet fed control. The respective diets were fed for first 6 months and then half of the atherogenic and stock diet fed monkeys were bilaterally vasectomised. The remaining monkeys were sham-vasectomised. At the end of one year, norepinephrine infusion was given to all the monkeys each day for 2 hrs, for 3 consecutive days and animals sacrificed after 96 hrs. Although serum lipids were not altered following vasectomy, platelet aggregation response was significantly enhanced in atherogenic diet fed animals. ECG changes were suggestive of acute myocardial ischaemia in 4 monkeys, 2 each from gp. I and II. Histopathology of heart revealed patchy myocardial necrosis and haemorrhage only in one monkey of gp. I, while others had fuchsinorrhagia indicating ischaemic change. These findings are in contrast to those seen in vasectomised human subjects.
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Twelve rhesus and one pig-tailed macaque have been monitored for 28-41 months following experimental infection with 10(4) TCID of SIV/SMM. Twelve of the 13 animals became virus positive and seroconverted within 3 to 6 weeks of exposure; the remaining animal seroconverted at 6 months, but has remained virus negative. Six of the 13 animals (46%) died between 14 and 28 months post-infection, following prolonged clinical disease characterized by chronic diarrhea and weight loss, peripheral lymphadenopathy and hemogram abnormalities. Histologic findings ranged from prominent follicular hyperplasia to severe lymphoid depletion, with lymphoid tissues often showing an infiltrate of syncytial giant cells. One animal had intestinal cryptosporidiosis and two had brain lesions comparable to those seen in AIDS encephalopathy in humans. Three of the remaining seven animals have an ARC-like disease and are showing gradual deterioration of their clinical condition. These animals, as well as animals that died, had progressive decreases in CD4+ cells and CD4+/CD8+ cell ratios. These observations further document the marked clinical, pathologic and immunologic similarities between human AIDS and the SIV-infected macaque model.
The present study was designed to comparatively investigate 34 beta-hemolytic streptococci isolated from infected pigs and monkeys from various islands in Indonesia. According to the serological and biochemical data, all 34 isolates were Lancefield's serological group C streptococci and could be identified as Streptococcus equi subsp. zooepidemicus. Of the 34 group C streptococci investigated, 28 grew on solid media in large, mucoid colonies, in fluid media at a uniform turbidity, and in soft agar in diffuse colonies. A decapsulation test with a hyaluronidase-producing Staphylococcus aureus strain revealed the hyaluronic acid nature of the capsular material. The remaining six streptococci grew on solid media in small, nonmucoid colonies, in fluid media as sediment with clear supernatant, and in soft agar in compact colonies. Determination of surface hydrophobicity by salt aggregation revealed a hydrophilic surface for the encapsulated bacteria and a hydrophobic surface for the unencapsulated group C streptococci. To further analyze the epidemiological relationships, all 34 mucoid and nonmucoid isolates from pigs and monkeys were subjected to protein and DNA fingerprinting. The latter was performed by pulsed-field gel electrophoresis. The protein profiles of all 34 isolates and the DNA profiles of 32 isolates appeared to be identical, with the DNA profiles of 2 isolates being closely related, indicating that a single virulent clone is responsible for this disease outbreak in Indonesia.
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Rhesus monkeys that were maintained on a diet containing low, yet adequate, amounts of vitamins C and E and in which linoleate and linolenate represented 1.4% and 0.08% of the total caloric intake, respectively, developed liver fibrosis after consuming alcohol (mean, 2.6 g kg(-1) d[-1]) over a period of 3 years. In the liver, several polyunsaturated fatty acids including 18:2n6, 20:4n6, and 22:6n3 decreased compared with dietary controls, and similar findings were also observed in plasma lipoproteins and erythrocytes. The amount of alcohol consumed correlated positively with plasma lipid peroxidation products, 4-hydroxynonenal (4-HNE) and 8-isoprostane F2alpha, and negatively with 20:4n6 and 22:6n3 levels. These findings imply that alcoholics who also have a marginal intake of essential fatty acids and antioxidants in their diets may be at an increased risk of developing liver disease.
The oviducts of two grivet monkeys and three marmosets, all sexually mature animals, were inoculated with Mycoplasma genitalium at laparotomy. The mycoplasma was not recovered from the grivet monkeys, nor from the oviducts of the marmosets although it was isolated intermittently from the vagina of two of the latter animals up to 4-6 weeks after inoculation. In contrast, all of the animals developed antibody to M. genitalium measured by a micro-immunofluorescence technique. It developed rapidly in the grivet monkeys but slowly in the marmosets, being detected first about 1 month after inoculation with a maximal response by 2 months. Furthermore, despite an absence of vaginal discharge or cytological response, all the animals developed a moderate to severe endosalpingitis characterized by the infiltration of acute inflammatory cells into the tubal epithelium, together with a lumenal exudate and adhesions between the mucosal folds. The changes are similar to those produced by Chlamydia trachomatis in simian models and naturally in women.
The T-cell tropic retrovirus of macaque monkeys STLV-III has morphologic, growth, and antigenic properties indicating that it is related to HTLV-III/LAV, the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Four of six rhesus monkeys died within 160 days of STLV-III inoculation with a wasting syndrome, opportunistic infections, a primary retroviral encephalitis, and immunologic abnormalities including a decrease in T4+ peripheral blood lymphocytes. These data show that an immunodeficiency syndrome can be produced experimentally in a nonhuman primate by an agent from the HTLV-III/LAV group of retroviruses. The STLV-III-macaque system will thus provide a useful model for the study of antiviral agents and vaccine development for human AIDS.
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Four patterns of structural alterations were found in lymph nodes (LNs) from rhesus monkeys 17 to 34 months after infection with simian immunodeficiency virus (SIV-mac251). SIV p27gag antigen and viral particles were localized either between the processes of follicular dendritic cells (FDCs) or in the cytoplasm of macrophages. In hyperplastic follicles, enlarged germinal centres contained numerous Ki67+ proliferating centroblasts which were rather rare in light zones occupied by the CD23+ FDC network. Involuted follicles contained a small number of Ki67+ centroblasts and the CD23 labelling was limited to a very small apical zone. A correlation was found between the morphological characteristics of the follicles (hyperplasia-involution) and the level of expression of the vascular cell adhesion molecule 1 (VCAM1) on FDCs. A gradient in VCAM1 intensity with no expression in the subcapsular-intermediary sinuses, low membrane labelling in the mantle and strong expression in the FDC network was observed. IL1 alpha+ and IL6+ (interleukin) cells (lymphocytes and macrophages) were detected in the mantle, the interfollicular area and the medulla of LNs. Expression of the tumour necrosis factor alpha and ultrastructural markers of interferon alpha production were found in a few FDC and macrophages. Our findings indicate a close relationship between the morphofunctional properties of FDC and the LN structure in SIV infection.