No evidence for prolonged excretion of polioviruses in persons with residual paralytic poliomyelitis in Ethiopia, Pakistan and Guatemala.

Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.     

THE PRECIPITATION OF CLINICAL POLIOMYELITIS BY INJECTIONS

In records of 1,321 cases of poliomyelitis in the city of Los Angeles in 1948, notation was made as to whether or not the patient had been vaccinated against smallpox or had received an injection of one kind or another in the period preceding the onset of poliomyelitis.In children under 12 years of age, the incidence of poliomyelitis was slightly higher among those who had had recent vaccination or injection than among those who had not, and the incidence of paralysis was slightly greater also. However, the disparities were not considered statistically significant. They were not wide enough to warrant withholding immunization against other serious diseases on the strength of the possibility that in so doing a slight reduction in the incidence of crippling poliomyelitis might be effected.     

Monoclonal antibody protection from age-dependent poliomyelitis: implications regarding the pathogenesis of lactate dehydrogenase-elevating virus.

Over 90% of cyclophosphamide-treated, 6- to 7-month-old C58/M mice developed fatal paralytic disease after infection with a virulent strain of lactate dehydrogenase-elevating virus (LDV), with a mean onset of paralysis of about 16 days. Passive immunization with polyclonal antibodies or with a group of anti-LDV monoclonal antibodies (MAbs) with single-epitope specificity 1 day before or at the time of LDV infection prevented the development of paralytic disease without interfering with the replication of LDV in permissive macrophages, the primary host cells of LDV. In situ hybridization of spinal cord sections with an LDV-specific cDNA probe indicated that the MAb specifically prevented the cytocidal infection of motor neurons by LDV without blocking the infection of smaller nonneuronal cells in the spinal cord. The protective antibodies recognize at least two different epitopes on the glycoprotein of LDV, VP-3. Passive immunizations with other anti-LDV MAbs, which recognize at least three other epitopes on VP-3 of LDV, afforded no protection. In contrast to the protective effect of anti-LDV MAb injection before or at the time of LDV infection, their administration postinfection exerted relatively little protection, though it delayed the appearance of paralytic symptoms. However, repeated injections of MAbs until at least 7 days postinfection also afforded a high degree of protection. The results indicate that protective MAbs may interfere with two stages in the development of LDV-induced paralytic disease. When administered at the time of LDV infection, they prevent the initial infection of spinal cord motor neurons. After this initial event, repeated injections of MAb are required to inhibit the spread of LDV between neurons until the endogenous production of protective anti-LDV antibodies in these mice.     

Role of immunity in age-related resistance to paralysis after murine leukemia virus infection.

Resistance to the paralytic effects of a wild mouse (Cas-Br-M) murine leukemia virus infection develops with age and is complete by 10 days of age in susceptible NFS mice. The possibility that cell-mediated immunity plays a significant role in this resistance was suggested by the observation that treatment of 10-day-old mice with antithymocyte serum rendered them susceptible to paralysis. By comparison, mice rendered incapable of generating a humoral immune response by treatment from birth to 1 month of age with anti-immunoglobulin M serum did not develop paralysis after challenge with virus at day 10. Transfer of unseparated and T-cell-enriched populations of Cas-Br-M murine leukemia virus-immune spleen cells protected neonatally infected NFS recipients from paralysis; transfer of Cas-Br-M murine leukemia virus-immune populations enriched for B cells delayed the onset but did not ultimately protect neonatally infected NFS mice from paralysis. Transfer of naive adult spleen cells had no protective effect in neonatally infected NFS mice. High-level virus replication occurred in the spleens and brains of all mice that developed paralysis regardless of treatment; low-level virus replication in spleen and barely detectable replication in brain occurred in mice that remained clinically normal. These studies suggest that the age-acquired resistance to the paralytic effect of Cas-Br-M murine leukemia virus infection is immunologically mediated and that T cells may play a major role.     

川硬皮肿腿蜂毒液对寄主黄粉虫蛹的影响

为揭示川硬皮肿腿蜂寄生对寄主黄粉虫蛹的调控机制,本文通过自然寄生和毒液注射等方法研究了寄生过程中蜂毒液的作用.结果表明: 对人工注射的蛹,寄主被麻痹的程度与毒液注入量呈正相关,恢复活动情况与毒液注入量呈负相关;当人工注射毒液浓度为0.01 VRE时,黄粉虫表现出可逆的轻微麻痹;当浓度提高到0.2 VRE时,黄粉虫蛹表现出不可逆的完全僵化.单独注射土壤菌液,导致蛹大量死亡并出现大范围的黑化现象,而注射毒液和土壤菌液混合物,蛹的黑化作用发生延缓,且死亡率显著下降.对毒液的抑菌测试表明,毒液对金黄葡萄球菌的抑菌作用显著高于大肠杆菌.在一定温度范围内,随着温度升高毒液麻痹活性显著降低,对大肠杆菌抑菌性显著升高,对金黄葡萄球菌抑菌性显著降低.表明川硬皮肿腿蜂毒液对寄主黄粉虫蛹具有麻痹、抑菌、抑制蜕皮和延缓黑化的作用.     

Botulinum toxin injections as a method for chemically denervating skeletal muscle to test functional hypotheses: a pilot study in Lepomis cyanellus

In this study, we demonstrate that botulinum toxin can be used to chemically denervate muscles to test functional hypotheses. We injected research-grade type A botulinum toxin complex into pectoral fin abductors (abductor superficialis) of green sunfish (Lepomis cyanellus) to determine whether chemical denervation would eliminate the ability of a particular muscle to contribute to overall pectoral fin movements. Reduction of target muscle activity occurred within 8 d of the injection, and paralysis was confirmed using electromyography. No paralysis was seen in the adjacent muscles (abductor profundus) or in positive controls (saline injections). Paralysis occurred more slowly and at lower doses than previously documented for mammals. However, botulinum toxin complex (500 kDa) was used here, whereas previous studies have used purified toxin (150 kDa). Therefore, differences in physiological responses between fish and mammals cannot yet be distinguished from differences caused by the toxin type. However, we note that the toxin complex is less likely to diffuse across muscle fascia (because it is large), which should minimize paralytic effects on adjacent muscles. We suggest that botulinum toxin holds great promise as a chemical denervation agent in functional studies of animal locomotion and feeding behaviors.     

Comparison of the effects of botulinum neurotoxin types A and E at the rat neuromuscular junction

Local blockade of transmitter release was produced by s.c. injection of purified botulinum neurotoxin (NT) types A or E above the tibialis anterior muscle of adult male rats. Extensor digitorum longus nerve-muscle preparation was examined for toxin-induced alterations in single twitch and tetanic tension (in situ) or transmitter release (in vitro). For both single twitch and tetanic tension, muscles treated with type E NT recovered from an initial partial paralysis (induced with 56 mouse LD50) or full paralysis (induced with 565 mouse LD50) by 7 days after NT injection, while those treated with only 5 mouse LD50 of type A remained either fully or partially paralysed through 10 days. Also, miniature end-plate potential frequency and mean quantal content were reduced for a longer period of time and/or to a greater extent for muscles treated with type A NT than for those treated with type E. The present results are consistent with the observed higher specific toxicity (i.p. injections in mice) for type A NT than for type E, although these differences may be exaggerated after s.c. injections. The differences in the paralytic effect between types A and E may be determined by differences in amino acid sequence, which causes type E to dissociate more easily from its site of action and/or be detoxified more rapidly. The clinical implications of these findings are discussed.     

Prevention of infections hepatitis by gamma globulin

Infectious hepatitis, a viral disease, has become increasingly more important in recent years. It is believed that the great increase in reported cases is not due entirely to better reporting, but that there has been an actual increase in the incidence of this disease. The comparatively long incubation period in infectious hepatitis, the high incidence in persons in close contact with patients who have the disease, and the fact that in most instances contact between persons is the mode of spread, makes this disease particularly suitable for the use of an immunizing agent which would be administered after exposure. From the studies reviewed it is apparent that gamma globulin is of value in preventing hepatitis both when administered as mass prophylaxis in an epidemic, and when given to persons in close contact with a person who has the disease. Widespread use of gamma globulin prophylactically among persons who have been in close contact with the occasional patients with infectious hepatitis seen by practicing physicians might often obviate the need for mass immunization. It should be stated that there is little evidence for the effectiveness of gamma globulin in the therapy of infectious hepatitis. In a study in which very large amounts (average dose 45 cc.) of gamma globulin were given very early in the disease, no significant difference was observed between those injected and a control group.     

PREVENTION OF INFECTIOUS HEPATITIS BY GAMMA GLOBULIN

Infectious hepatitis, a viral disease, has become increasingly more important in recent years. It is believed that the great increase in reported cases is not due entirely to better reporting, but that there has been an actual increase in the incidence of this disease. The comparatively long incubation period in infectious hepatitis, the high incidence in persons in close contact with patients who have the disease, and the fact that in most instances contact between persons is the mode of spread, makes this disease particularly suitable for the use of an immunizing agent which would be administered after exposure.From the studies reviewed it is apparent that gamma globulin is of value in preventing hepatitis both when administered as mass prophylaxis in an epidemic, and when given to persons in close contact with a person who has the disease. Widespread use of gamma globulin prophylactically among persons who have been in close contact with the occasional patients with infectious hepatitis seen by practicing physicians might often obviate the need for mass immunization. It should be stated that there is little evidence for the effectiveness of gamma globulin in the therapy of infectious hepatitis. In a study in which very large amounts (average dose 45 cc.) of gamma globulin were given very early in the disease, no significant difference was observed between those injected and a control group.     

Pathogenesis of age dependent paralysis by a temperature sensitive mutant (tsl) of Moloney murine leukemia virus-TB.

The tsl mutant of Moloney murine leukemia virus-TB produces neurological disease leading to fatal hind limb paralysis when inoculated in newborn BALB/c mice. The present study was under taken to assess the role of T and B lymphocytes in age dependent resistance to tsl induced paralysis in BALB/c mice. The adoptive transfer of non-immune splenic unseparated lymphoid cells, T cells and B cells and tsl immune B cells and T cells to newborn BALB/c mice infected with tsl did not prevent the development of paralysis. However, adoptive transfer of immune splenic unseparated lymphoid cells and immune T cells delayed the onset of paralysis by 5 to 10 days as compared to the mice which did not receive the immune lymphocytes. Athymic BALB/c nude mice inoculated with tsl at days 1 and 10 after birth failed to develop the paralytic disease. Transfer of tsl neutralising antibody also delayed the onset of paralysis. Mice (10 days old) treated with cyclophosphamide, cyclosporine A, cortisone acetate and anti-T cell serum when inoculated with tsl also did not develop neurological disease. The results suggest that age related resistance to neurological disease may not be associated with B cell mediated immunity.     

Safety and immunogenicity of ALVAC vCP1452 and recombinant gp160 in newly human immunodeficiency virus type 1-infected patients treated with prolonged highly active antiretroviral therapy

In order to boost immune responses in persons in whom highly active antiretroviral therapy (HAART) was initiated within 120 days of the onset of symptoms of newly acquired human immunodeficiency virus type 1 (HIV-1) infection, we administered vaccines containing a canarypox virus vector, vCP1452, with HIV-1 genes encoding multiple HIV-1 proteins, and recombinant gp160. Fifteen HIV-1-infected subjects who achieved sustained suppression of plasma viremia for at least 2 years were enrolled. While continuing antiretroviral therapy, each subject received at least four intramuscular injections of the vaccines on days 0, 30, 90, and 180. Adverse events were mild, with the most common being transient tenderness at the vCP1452 injection site. Of the 14 patients who completed vaccination, 13 had significant increases in anti-gp120 or anti-p24 antibody titers, and 9 had transient augmentation of their T-cell proliferation responses to gp160 and/or p24. HIV-1-specific CD8(+) T cells were quantified using an intracellular gamma interferon staining assay. Among 11 patients who had increased CD8(+) T-cell responses, seven had responses to more than one HIV-1 antigen. In summary, vaccination with vCP1452 and recombinant gp160 appears safe and immunogenic in newly HIV-1-infected patients on HAART.     

Huntington disease in Georgia: age at onset.

Age at onset of motor symptoms was collected on 611 persons affected with Huntington disease (HD) among 3,201 persons "at risk" in 108 kindreds. Life-table estimates correcting for truncated intervals of observation (censoring) produced a median age at onset 5 years older than the observed mean. Risk estimates of HD onset for persons at risk, as calculated by life-table methods, were significantly higher for older ages than were estimates based on the observed distribution of onsets. Age-specific incidence was found to be highest at age 35-64 years, a considerably older age interval than suggested by previous estimates. The offspring of affected males had significantly younger onset than did offspring of affected females, and a trend suggesting and excess of paternal descent among juvenile-onset cases was present. Life-table analysis is contrasted with analyses of (a) the observed distribution of age at onset and (b) remote cohorts age 63 or older at the time of data collection. The implications for risk prediction, genetic counseling, and genetic analysis of HD are discussed.     

Plasmodium berghei: inhibition by splenectomy of a paralyzing syndrome in infected rats

In recent attempts to isolate the factor causing paralysis in rats infected with a mousepassed KBG 173 strain of Plasmodium berghei Splenectomy was employed. The effects of Splenectomy on the paralyzing syndrome are discussed in the present report. Paralysis was inhibited in rats splenectomized prior to inoculation. Serial bloodpassaging of the strain in the splenectomized host however, apparently enhanced its virulence. Spleen-intact rats used as controls exhibited a marked increase in incidence of paralysis. Rats splenectomized a day before paralysis became evident were paralyzed significantly more frequently than those splenectomized a day earlier, indicating the apparent requirement of an incubation period for the expression of the paralytic effect. The enhanced virulence did not appear to be related to the level of parasitemia of the splenectomized rats used as donors. The spleen appears to provide the optimal conditions required for the elaboration of the paralyzing factor.     

Mechanism of Injury-Provoked Poliomyelitis

Skeletal muscle injury is known to predispose its sufferers to neurological complications of concurrent poliovirus infections. This phenomenon, labeled “provocation poliomyelitis,” continues to cause numerous cases of childhood paralysis due to the administration of unnecessary injections to children in areas where poliovirus is endemic. Recently, it has been reported that intramuscular injections may also increase the likelihood of vaccine-associated paralytic poliomyelitis in recipients of live attenuated poliovirus vaccines. We have studied this important risk factor for paralytic polio in an animal system for poliomyelitis and have determined the pathogenic mechanism linking intramuscular injections and provocation poliomyelitis. Skeletal muscle injury induces retrograde axonal transport of poliovirus and thereby facilitates viral invasion of the central nervous system and the progression of spinal cord damage. The pathogenic mechanism of provocation poliomyelitis may differ from that of polio acquired in the absence of predisposing factors.     

Correlation of HLA-Cw*06 allele frequency with some clinical features of psoriasis vulgaris in the population of northern Poland

Psoriasis is a common skin disease with a genetic background and significant human leukocyte antigen (HLA) associations. HLA-Cw6 is the most frequently described association, particularly with psoriasis of the early onset type. Few studies of its correlation with various psoriasis clinical phenotypes and severity of the disease have been published so far; none in the Polish population. In this study 78 patients with psoriasis vulgaris were evaluated clinically and subdivided according to the age of onset and the type of psoriasis. A system of disease severity evaluation was applied to each patient. All patients and the control group (70 unrelated persons) were typed for HLA-Cw*06. The results show that Cw*06 allele frequency was higher in psoriatics than in the control group. Our investigation confirms that the Cw*06 allele is positively associated with psoriasis vulgaris of the early onset type, with a positive family history and its more severe form.     

Bronchogenic carcinoma in San Diego County; relation of mortality rates to findings in mass chest x-ray survey

Nearly half the population of San Diego County was examined by chest x-ray for bronchogenic carcinoma. The disease was correctly diagnosed in 20 persons, of whom 17 died. Twenty-four others in whom it was not detected in survey films died of the disease in the following two years. Of the 20 cases found, 16 were in men, all more than 54 years of age, and of the 24 who died after "negative" classification, 20 were men over 40. The death rate for men over 40 years of age from bronchogenic carcinoma is about one in a thousand. Because of the frequently rapid progress of the disease after onset, and the poor prognosis after the appearance of symptoms, x-ray examination every six months for men over 40 should be considered.     

Speed, Sex, Gay Men, and HIV: Ecological and Community Perspectives

Fifteen years into the HIV/AIDS epidemic, a great deal is now known about the different populations impacted by the disease, including those affected directly or indirectly by drug use. Anthropology has played a critical role in assisting with this task by identifying hidden populations, developing new methodological approaches, and targeting outreach efforts. In spite of this considerable body of ethnographic knowledge, men who have sex with other men (i.e., MSM, or gay and bisexual men) who use drugs have not received the same research attention as other drug users, despite the fact that they represent nearly one-fifth of AIDS cases in the U.S. with injection drug histories. In response to the alarming increase in HIV seroprevalence among this population, this ethnographic project provides preliminary data about those who are at dual risk for HIV through both homosexual behavior and injection drug use.     

The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Macaque Species

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction.     

The presence of specific antigen-reactive cells during the induction, recovery, and resistance phases of experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) is an induced disorder in which an autoimmune response specific for myelin basic protein (BP) results in neural tissue destruction and acute paralysis. Lewis rats rapidly recover from induced paralysis and do not display any clinical manifestations of EAE following a second BP injection. The object of this study was to determine if immunologic recognition of encephalitogenic fragments of the BP molecule occurs during the induction, recovery, and resistance phases of EAE. Paralysis was induced in Lewis rats by a single injection of BP in complete Freund's adjuvant (CFA). The results indicate that macrophage migration inhibition in the presence of encephalitogenic BP fragments containing amino acid residues 43–88 and 68–88 is detectable during the paralytic stage of EAE, and also following recovery from clinical neurologic impairment. Although rats which had recovered were resistant to secondary BP-induced paralysis, macrophage migration inhibition in the presence of BP, or its encephalitogenic fragments, was detected after the second BP-CFA challenge. In order to assess humoral immunologic recognition, levels of serum antibody specific for the 43–88 BP fragment were determined. Specific antibody was not detected during the paralytic episode, but appeared upon recovery. Specific antibody was also detected following the secondary BP-CFA challenge. These data indicate that antigen-sensitive cells are present during the induction, recovery, and resistance phases of EAE in the Lewis rat. The mechanism which controls the activity of these cells in vivo has not been established.     

Work with youth--the basis of educational programs aimed at the prevention of HIV infection

During the recent 10 years, 1987-1997, syphilis morbidity was found to increase 60-fold in Omsk Province. In 1997 adolescents constituted 6.0% in the structure of persons who contacted the disease. In this year more than 500 adolescent using drugs were registered in the region. The introduction of drugs by injection was practiced by 9.6% of the adolescents. The program aimed mainly at changing the behavior of young people with orientation on the choice of a healthy mode of life and theirs information about risk factors associated with sex transmitted diseases particularly HIV infection is discussed.