[Pain fluctuations in Parkinson's disease].

OBJECTIVE: To specify the character of pain syndromes and determine their relationship with main symptoms of ON and OFF periods in patients with complications of long-term treatment with levodopa medications. MATERIAL AND METHODS: Authors examined 40 patients with Parkinson's disease (27 women and 13 men), mean age 69.2±8 years (from 62 to 85 years), illness duration 9.2±1.2 years (from 7 to 11 years), duration of treatment with levodopa 6.9±1.2 years (from 5 to 9 years). The severity of disease course, character and intensity of pain syndrome were assessed. RESULTS AND CONCLUSION: We described pain syndromes that had differences in the pathogenesis and localization. Adjustment of the antiparkinsonian treatment resulted in the decrease in their severity. Motor fluctuations and drug-induced dyskinesia that was accompanied by pain sensations were the most frequent signs of Parkinson's disease during its progression. The pain syndrome was related to main symptoms of the ON and OFF period in patients with complications of long-term treatment with levodopa. The pain fluctuations had both nociceptive and central neuropathic pain phenotypes.

Inbreeding, heterozygosity, and lymphoma risk among the baboons (Papio hamadryas) of Sukhumi, USSR.

This paper describes the spread of lymphoma through a baboon (Papio hamadryas) colony in the Institute of Experimental Pathology and Therapy at Sukhumi, USSR. In the late 1960s, Soviet scientists inoculated 12 baboons with cells from hospitalized human leukemia patients, causing the death of a total of 135 animals between 1967 and 1978. The death rate from lymphoma averages almost 12 baboons per year in the Sukhumi colony. Genetic investigations of these baboons revealed the following: 1) Six blood protein markers out of 16 systems (38%) tested were polymorphic; 2) the average inbreeding coefficient for the entire colony (N = 1,226) was 0.027 (exclusion of baboons with F values equal to 0.0 raised the mean inbreeding coefficient to 0.096); 3) no relationship between inbreeding and risk of lymphoma was noted; and 4) there was an apparent association between both PGM loci and the incidence of lymphoma at the 0.005 levels of significance. This association was further supported by the significantly lower incidence of PGM2 (2-1) genotype in baboons with high anti-VCA-HVP titers.

Lymphocyte sensitization detected in lymphomatous hamadryas baboons by the macrophage electrophoretic mobility assay.

Peripheral blood lymphocytes from lymphomatous or control Papio hamadryas monkeys were incubated in the presence of KCl-extracted proteins prepared from allogeneic lymphomatous or normal lymph nodes and from a spontaneous baboon hepatoma. Only the lymphomatous baboon lymphocyte-lymphoma antigen interaction product(s) significantly reduced the anodic electrophoretic mobility of guinea pig macrophages.

Immunophenotypical characteristics of permanent cultures of lymphoid cells from Papio hamadryas and Macaca arctoides.

Immunophenotypical characteristics of primate cells were studied by enzyme immunoassay and flow cytofluorometry using a panel of monoclonal antibodies to human B- and T-lymphocyte antigens. Specific features of immunophenotype of cultured cells were detected. Simian lymphoid cultures consist of a mixture of B- and T-cells with mosaic antigenic structure expressing markers of B and T cell specificity.

Neutralizing antibodies to simian papovavirus SA12 in Old World primates in laboratory colonies: high prevalence in baboons.

Sera from 517 laboratory-housed nonhuman primates representing five genera and from 13 laboratory workers were examined for the presence of neutralizing antibodies to SA12 virus. The antibody prevalences were as follows: baboons, 66%; patas and vervet monkeys, 24%; macaques, 8%, and chimpanzees, 2%. The serum of one laboratory worker had antibodies. These results suggest that SA12 virus is a common infection of nonhuman primates in laboratory colonies, especially baboons.

Increased antibody responses to Herpes virus papio (HVP) antigens in pre-lymphomatous baboons (Papio hamadryas) of the Sukhumi high lymphoma stock.

Antibody responses to Herpes virus papio (HVP) antigens were studied in 21 pre-lymphoma baboons (which subsequently died of malignant lymphoma), 21 paired controls, i.e. age-, sex- and population-matched healthy baboons, and 185 randomly selected healthy baboons of the same population. The sera were all collected at the same time and were tested blind in the fixed-cell indirect immunofluorescence test against HVP viral capsid antigen (VCA)-positive, early antigen (EA)-positive cell targets before and after absorption with HVP. Eleven of the pre-lymphoma sera were anti-EA-positive whereas none of the paired controls contained anti-EA. Anti-VCA titers of pre-lymphoma sera were higher than those of paired controls in thirteen cases. Only in four cases were anti-VCA titers of pre-lymphoma sera lower than those of paired controls. Qualitatively, the same results were obtained when anti-VCA and anti-EA titers of pre-lymphoma sera were compared with respective mean population values. The differences between pre-lymphoma group and control groups, especially in the case of anti-EA, were statistically highly significant. Thus, elevated anti-HVP titers in healthy baboons of the Sukhumi lymphoma-prone stock can be considered as a marker of high risk for development of malignant lymphoma.

Proteins and glycoproteins of monkey and human platelets. Comparison by high resolution two-dimensional gel electrophoresis.

1. The protein and glycoprotein composition of the blood platelets of six primate species have been compared by high resolution two-dimensional polyacrylamide gel electrophoresis. 2. Only minor differences have been observed in the protein patterns of all six species. 3. The glycopeptide patterns of the monkey platelets five species) were rather uniform, but clearly different from the human pattern.

Antibodies reacting with human T-lymphotropic retrovirus (HTLV-I) or related antigens in lymphomatous and healthy hamadryas baboons.

The sera of lymphomatous and healthy hamadryas baboons of the main, lymphoma-prone Sukhumi stock were tested for antibodies reacting with HTLV-I antigens in the indirect immunofluorescence test. Antibodies of this specificity were found in all but one of 58 lymphomatous baboons and in 45% of 177 healthy ones. The prevalence of HTLV-I reactive antibodies in lymphoma-free baboon populations (including 118 Sukhumi "forest" stock animals and 195 baboons imported in 3 groups from Ethiopia) was consistently lower (5-8%). The specificity of baboon antibodies reacting with HTLV-I or a related agent is supported by the following evidence: Concordant reactivity pattern of baboon sera with several HTLV-I-positive and-negative human cell lines; elimination of baboon sera anti-HTLV reactivity by absorption with purified HTLV-I, but not by other retroviruses; significant correlation between immunofluorescence titers of baboon sera and their reactivity in enzyme-linked immunosorbent assay with purified HTLV-I; competition of baboon anti-HTLV with monoclonal antibodies GIN-14 for binding of the epitope on p19HTLV-I. The prevalence of anti-HTLV positives in the main Sukhumi stock increased by age, reaching its maximum (approx. 80%) at 5-15 years, and showed no significant sex-related variation. The level of anti-HTLV antibodies in lymphomatous baboons and in age-, sex- and population-matched healthy ones did not differ. However, in pre-lymphoma sera these antibodies reached significantly higher levels than in sera of lymphomatous baboons (obtained in the terminal stage) or of matched, healthy controls.

Immunological investigation of the prelymphoma period in baboons of the Sukhumi monkey stock.

In the "pre-lymphoma" period, some high-risk baboons develop changes in their immunity which is expressed, in particular, in the imbalnace of T-lymphocyte subpopulations, that is, increase in the number of cells of T gamma subpopulation which are carriers of suppressive functions in man. As a reflection of immunological disturbances, increase in the level of antibodies against HVP, apparently as a result of HVP activation, is observed in baboons in the "pre-lymphoma" period.

Continuous lymphoblastoid suspension cultures from cells of haematopoietic organs of baboons with malignant lymphoma--biological characterization and biological properties of the herpes virus associated with culture cells.

The continuous lymphoblastoid cell lines KMPG-1 and SPG-2 producing baboon herpes virus (HVP) with morphological signs of herpes viruses have been established from haematopoietic organs of lymphomatous baboons. As distinct from H.simplex type I and II viruses HVP is not pathogenic for laboratory rodents. According to its physico-chemical and immunological properties HVP is related to the Epstein-Barr virus.

Isolation of a primate type-C virus from a lymphomatous baboon.

A type-C RNA virus has been isolated from various tissues of a lymphomatous baboon (sp. P hamadryas). Virus isolations were made by co-cultivating baboon cells from the inguinal and mesenteric lymph nodes, testes, kidneys and spleen with cells of canine or human origin. The isolated virus grew in canine, bat, rhesus, and human cells but not in cells of mouse, rat, cat or rabbit origin. The baboon isolate resemble a type-C virus when infected cells were examined by thin section in the electron microscope. In addition, the virus was capable of providing helper function by rescuing and transmitting the Moloney and Kirsten sarcoma virus genome from non-productively transformed cells. Antibody directed against the RD114 virus reverse transcriptase was very effective in inhibiting the baboon virus polymerase while while anti-mouse and woolly type-C virus polymerase antibodies had no significant inhibitory activity. Further analysis by immunodiffusion and competitive radioimmune assay revealed a close immunological relationship between this virus, RD114 and another type-C virus isolated from the placenta of a different species of baboon. Finally, three different classes of interspecies antigenic determinants have been demonstrated in mammalian type-C virus isolated from the placenta of a different species of baboon. Finally, three different classes of interspecies antigenic determinants have been demonstrated in mammalian type-C viruses.

Prevalence of antibodies to soluble antigen of Epstein-Barr virus-producing cells (P3HR-1) in the sera of hamadryas baboons of the high lymphoma incidence stock.

Soluble antigen of P3HR-1 cells (SA-P3HR-1) was identified in indirect double immunodiffusion enhanced with tannic acid using serum of a nasopharyngeal carcinoma patient containing high-titer antibodies to Epstein-Barr virus (EBV) antigens. SA-P3HR-1 was nonidentical to soluble antigen of Raji cells. Human and baboon sera containing antibodies to all the known antigen of EBV and HVP respectively were anti-SA-3HR-1-positive. Human and baboon sera containing antibodies to all the known antigens of EBV and herpesvirus Papio (HVP) were also anti-SA-P3HR-1-negative. Prevalence of anti-SA-P3HR-1 was very high in two groups of the high-lymphoma incidence stock of hamadryas baboons of the Sukhumi monkey colony. 54% (15 of 28) and 38% (13 of 34) of clinically lymphomatous and clinical normal monkeys, respectively, were anti-SA-P3HR-1-positive.. Only 1 of 30 normal baboons studied, living in the forest and having no contacts with the baboons in the main stock of the Sukhumi monkey colony, was anti-SA-P3HR-1-positive (3%).

Antibody responses to Herpesvirus papio antigens in baboons with lymphoma.

An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were not age- or sex-related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did not indicate a disease-related role for either of these viruses.

Morphological characteristics of malignant T-cell lymphomas in baboons.

Fifteen cases of generalized peripheral T-cell non-Hodgkin's lymphoma in baboons were phenotyped immunologically and morphologically. Using the updated Kiel classification the cases included low-grade and high-grade lymphomas and low-grade lymphomas that had transformed into high-grade lymphomas. In the low-grade group there were seven cases of lymphocytic type, partly corresponding to chronic lymphocytic leukaemia of T type and to T-zone lymphoma in man. In addition there were four cases of prolymphocytic-lymphocytic type, which show large nodules ("proliferation centres") and which have no equivalent in the Kiel classification. In four cases there was a progression to an immunoblastic lymphoma and in one case to a large cell anaplastic lymphoma. In addition, three cases of large cell anaplastic lymphoma without a low-grade component were found. Both the immunoblastic lymphomas and the large cell anaplastic lymphomas corresponded well with the same types in the Kiel classification. The cases of large cell anaplastic lymphoma were also CD30 positive. Most of these lymphomas were CD4 positive, but there were rare cases that were either CD8 positive, showed both CD4 and CD8 positivity or had lost both antigens. Antigens associated with cell activation were often revealed. All but one baboon had antibodies in the blood against the retrovirus STLV-1 (simian T-cell leukaemia virus 1), which is very similar to human T-cell leukaemia virus 1 (HTLV-1) in man. Despite this virological resemblance, the morphology of these T-cell lymphomas does not resemble that of the HTLV-1-positive Japanese T-cell lymphomas but is like that of the HTLV-1-negative European cases.

The establishment of continuous lymphoblastoid suspension cell cultures from hematopoietic organs of baboon (Papio hamadryas) with malignant lymphoma.

Two continuous suspension lymphoblastoid cell cultures designated as SPG-1 and KMPG-1 have been established from the bone marrow and spleen cells of the hamadryas baboon no. 9386 with malignant lymphoma. Virus particles morphologically characterized as herpes-like have been revealed in KMPH-1 and SPG-1 cultures in 2-10% of cells. The paper describes the establishment of these suspension cultures.

Transmission of human leukaemia to nonhuman primates.

The experiments described show that inoculation of two monkey species, M. arctoides and P. hamadryas, with human leukaemic blood or its filtrates causes a viral disease with the characteristics of malignant lymphoma of mixed type. The disease was passed in subsequent passages. The virus was isolated and identified as an oncornavirus of C-type by its characteristic morphological appearance and buoyant density (1.16 g/cm3 in sucrose and 1.21 g/cm3 in caesium chloride), and by the presence of 60-70S RNA and RNA-dependent DNA polymerase. There is some evidence that it differs immunologically from other known oncornaviruses of mammals including primates. It is postulated that both horizontal and vertical transmission of this oncornavirus can occur.

Continuous lymphoblastoid suspension cultures from cells of haematopoietic organs of baboons with malignant lymphoma. Report III: Immunological studies.

Lymphoblastoid cultures established from haematopoietic organs of baboons with lymphoma belong to the B-cell type. Cytoplasmic antigen is revealed in 2--6% of suspension culture cells established from lymphomatous baboons by indirect immunofluorescence reaction using serum from human Burkitt's lymphoma patients with antibody titer to capsid antigen of Epstein-Barr virus 1: 320. There is a correlation between the number of antigen-containing cells in these cultures and the number of cells in which herpes virus is revealed electron microscopically. Sera of baboons with lymphoma contain high titers of antibodies to Epstein-Barr (EBV) virus. Specific differences between antigens being produced in cultures by HBV (herpes virus of baboon) and EBV (Epstein-Barr virus) are minimal, that indicates their immunologic similarity.

Genetics of primate lymphomas in a baboon (Papio hamadryas) colony of Sukhumi, USSR.

A lymphoma outbreak occurred at the Sukhumi Center in the Late 1960's, when 12 baboons were inoculated with blood from human leukemia patients. Out of a total of 3219 animals, 218 contracted lymphoma and died. This outbreak appears to be primarily horizontal in transmission. Genetic investigations reveal that: (1) inbreeding does not increase risk of lymphoma; (2) there is a weak association between the PGM2 locus and lymphoma; (3) based upon path analysis, there is evidence of a significant transmissible component (genetic predisposition) passed from the parental to the next generation.

Baboon T cell lymphomas expressing the B cell-associated surface proteins CD40 and Bgp95.

Papio hamadryas baboons in the Sukhumi colony develop enzootic outbreaks of malignant lymphomas with an incidence of about 1.5% per year among adults of the high-risk stock. We investigated the surface phenotypes of cells from normal and lymphomatous animals using antibodies against human lymphocyte antigens. We found that more than 80% of the lymphomas that developed during the last 3 years were characterized histologically to be of the peripheral T cell type. Generally, the lymphomatous cells also expressed high levels of MHC class II DR protein, CD18 (LFA-1 beta chain), and CD45RO. Surprisingly, these cells also expressed on their surface two proteins previously characterized as being relatively B cell-restricted: CD40 and Bgp95. These proteins were never found on the peripheral blood T cells from normal animals. The expression of these two gene products was confirmed by RNA blotting and immunoprecipitation. In most cases, the two B cell-associated proteins were expressed on the predominant T cell subsets; we found both B cell proteins on CD4+, CD8+ as well as on the CD4/8 double-positive cells when these subsets were expressed at high levels. About 90% of these animals are seropositive for Herpesvirus papio and human T cell leukemia virus-1 (HTLV-1) before developing outright lymphomas. In all of the lymphoma samples, HTLV-1 tax DNA sequences were detected by PCR amplification. Whether or not HTLV-1 or the Herpesvirus papio gene products influence the surface expression of CD40 and Bgp95 remains to be determined.