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Biomedical subjects

H L Lucia

Publications and source records attributed to H L Lucia.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effect of cyclosporin A immunosuppression on primary lymphotropic herpesvirus infection in the guinea pig.

Female guinea pigs pretreated for 2 days with cyclosporin A (CsA), were then inoculated intranasally (IN) or intraperitoneally (IP) with a lymphotropic herpesvirus (GPHLV) and followed by 4 additional daily doses of CsA. Immunosuppressed animals did not show lymphocytosis and virus infectivity titers in their spleen, cervical lymph node and blood mononuclear cells were lower than those of oil-treated controls. While IN-inoculated CsA-treated animals expressed higher virus infectivity titer in their lungs compared to oil-treated controls, this difference was not seen in the IP-inoculated groups. At histopathology, lymphoid depletion was seen in all CsA-treated animals, but lymphocytic interstitial pneumonia was observed only in the lungs of IN-inoculated CsA-treated guinea pigs. Thus, CsA immunosuppression altered the pathogenesis of primary GPHLV infection with some notable differences attributed to the route of virus inoculation.

Administration, Intranasal↗
PubMed1987

Effects of cyclosporine on chronic cytomegalovirus infection in the guinea pig.

Following establishment of chronic guinea pig cytomegalovirus (GPCMV) infection, animals received by gavage either cyclosporine (CS), 20-33 mg/kg, or drug vehicle daily for 28 days. At sacrifice the frequency of CMV isolation from tissues of GPCMV-infected animals was 20% for the immunosuppressed group versus 12% for controls (difference, NS). GPCMV isolation rates from lymphoid tissues (thymus, spleen, cervical lymph nodes) of experimental animals was 7 of 69 (10%) vs. 0 of 42 (0%) from controls (p less than 0.05). Although CS immunosuppression was associated with increased rates of GPCMV isolation from lymphoid tissues of chronically infected animals, it was not accompanied by detectable systemic disease.

Animals↗
PubMed1986

Effects of cyclosporine and cortisone on the pathogenesis of primary infection with cytomegalovirus in the guinea pig.

Effects of the immunosuppressive agents cyclosporine (CsA) and cortisone on the pathogenesis of primary infections with cytomegalovirus (CMV) were investigated in the guinea pig model. All animals received 10(4) 50% tissue culture infectious doses of virulent salivary gland-passaged guinea pig CMV (GPCMV) subcutaneously on day 0. Oral CsA (20 mg/kg per day) and/or subcutaneous cortisone (10 mg/kg per day) were administered until the animals were killed on day 14. Untreated controls developed lymphocytosis, and GPCMV was isolated from 19.4% of cocultivated tissues. Animals treated with CsA alone developed lymphopenia, and GPCMV was isolated from 53% of their tissues, including 16 of 16 lungs. Histopathology showed widespread viral inclusions and minimal inflammatory response to GPCMV in CsA-treated animals. Guinea pigs treated with either cortisone or CsA/cortisone did not develop lymphopenia, and their rates of isolation of GPCMV were significantly lower than those of CsA-treated animals.

Animals↗
PubMed1985

Pulmonary macrophage function during experimental cytomegalovirus interstitial pneumonia.

Since cytomegalovirus (CMV) infections may alter host defense against a variety of pathogens, phagocytosis, oxygen uptake, and H2O2 release by pulmonary macrophages obtained from guinea pigs with acute CMV interstitial pneumonia were evaluated. Experimental animals were inoculated subcutaneously on day zero with 10(7.5) 50% tissue culture infective doses of virulent guinea pig CMV. Control animals received an uninfected salivary gland suspension. The animals were sacrificed on day 7; the tissues were cocultivated for virus isolation, and the lungs were lavaged to obtain pulmonary macrophages. CMV was isolated from buffy coat cells (96%), bone marrow cells (71%), whole lungs (77%), pulmonary macrophages (60%), and pulmonary granulocytes (49%). There was no significant difference between groups at sacrifice in the total number of macrophages obtained by pulmonary lavage or in the phagocytic activity of the macrophages in vitro. However, in CMV-infected animals, the maximum rates of O2 consumption in response to the soluble stimulus, phorbol myristate acetate, and the particulate stimulus, Staphylococcus aureus, were 47 and 55%, respectively, of the rates in uninfected controls. Total macrophage O2 consumption in CMV-infected animals was 32 and 37%, respectively, of control values in response to the same stimuli. In CMV-infected animals, the maximum rates of H2O2 release were 22% of those in simultaneous controls for both stimuli, and total H2O2 release was 30 and 25%, respectively, of that in controls in response to these stimuli. Such alterations in macrophage oxidative function may contribute to superinfection during CMV pneumonia.

Acute Disease↗
PubMed1985

The placenta as a site of cytomegalovirus infection in guinea pigs.

The development of cytomegalovirus (CMV) infection in the placenta was studied in Hartley guinea pigs inoculated at midgestation, and its role in determining the outcome of fetal CMV infection was assessed. A hematogenous spread of CMV from the mother to the placenta occurred early during the course of the infection. However, the virus remained present in placental tissues long after CMV had been cleared from maternal blood (i.e., 3 and 4 weeks postinoculation). At that time, the virus was able to replicate in placental tissues in the presence of specific maternal antibodies. Viral nucleocapsids were seen within nuclei of trophoblastic cells, and virions were present surrounding infected cells. In addition, typical CMV-induced histopathological lesions bearing CMV antigens were consistently localized at the transitional zone between the capillarized labyrinth and the noncapillarized interlobium. Whenever CMV infection of the fetus occurred, virus was isolated from the associated placenta. Among placental-fetal units with CMV-infected placentas, only 27% of the fetuses were found to be infected. In addition, there was a delay in the establishment of the infection in the fetus in relation to the placenta, although frequencies of virus isolation in placental and fetal tissues peaked at 3 weeks after CMV inoculation. These results suggest that during primary CMV infection of pregnant guinea pigs, the placenta not only serves as a reservoir for CMV but also acts to limit transmission of the virus to the fetus.

Animals↗
PubMed1985

Effects of cyclosporine on the pathogenesis of primary cytomegalovirus infection in the guinea pig.

The effects of cyclosporin A (CsA) upon the pathogenesis of primary cytomegalovirus (CMV) infection were investigated. Hartley and strain 2 guinea pigs were inoculated subcutaneously on day 0 with 10(4) TCD50 of virulent, salivary-gland-passaged guinea pig CMV and received oral CsA (20 mg/kg/day) for 14 days. CMV-infected, CsA-treated animals lost approximately 20% of their total body weight in 14 days and had more than twice the rate of CMV isolation from internal organs when compared with untreated controls, despite similar rates of viremia. Internal organs of CsA-treated animals demonstrated widespread viral inclusions and minimal inflammatory response to the presence of CMV-infected cells. The mean change in peripheral blood lymphocyte values for CMV-infected, CsA-treated Hartley guinea pigs was -2,867 +/- 2,955 (mean +/- SD) lymphocytes/microliters as compared to +10,933 +/- 7,583 in CMV-infected, untreated controls (p less than 0.01). In the guinea pig model, CsA administration had adverse effects upon the pathogenesis of primary CMV infection.

Animals↗
PubMed1985

Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs.

Hartley guinea pigs infected with guinea pig cytomegalovirus (GP-CMV) develop a mononucleosis syndrome during primary infection that is similar to that seen in immunocompetent humans. In the present study this animal model of human disease was used to investigate the sequential changes in the lymph nodes during the course of primary GP-CMV infection. Infectious virus could be isolated from the nodes up to eight weeks after inoculation. When compared with nodes of control animals, the nodes of GP-CMV-infected animals were found to be enlarged up to a year after infection. During the first ten days of infection, histologic changes due to virus proliferation and immune stimulation of the paracortical areas of the lymph node, in a diffuse hyperplasia pattern, were noted. Although typical cytomegalovirus inclusions were seen only rarely, many cells demonstrated intranuclear staining using an avidin-biotin immunoglucose-oxidase histochemical reaction for GP-CMV. During late acute and chronic infection, the lymph nodes showed immune stimulation of the germinal centers, in the pattern of follicular hyperplasia. Specific histologic changes related to active virus proliferation were not seen after the early acute phase.

Acute Disease↗
PubMed1984

A histochemical method for demonstrating papilloma virus infection in paraffin-embedded tissue.

In order to study the location of cells infected with human papilloma virus in paraffin-embedded tissues, the authors developed the following stain. Tissue sections were digested overnight with 0.01% deoxyribonuclease and then stained using the Feulgen stain with a light green counterstain. Cellular DNA was degraded, but viral DNA was not. Thus infected cells retained magneta nuclei, while uninfected cells stained a homogenous green. The stain was positive in 5/5 plantar warts, 7/8 verruca vulgaris, 2/2 laryngeal papilloma, and 18/20 condylomata accuminata. As a comparison, the indirect immunoperoxidase method on the same tissues stained 5/5 plantar warts, 6/8 verruca vulgaris, 0/2 laryngeal warts, and 2/20 condylomata accuminata. The presence of virus was confirmed by electron microscopic examination on one of the sections. Molluscum contageosum infected tissue also stained positively, but tissues infected with cytomegalovirus and herpes simplex virus did not. The only nonviral positive staining occurred with smears of sperm. The reasons for these results are discussed.

Animals↗
PubMed1984

Vaccination against transplacental cytomegalovirus transmission: vaccine reactivation and efficacy in guinea pigs.

The guinea-pig model of cytomegalovirus (CMV) infection was used in continuing studies of experimental CMV vaccines for prevention of congenital CMV infection. Low-passage guinea-pig cytomegalovirus (GPCMV) vaccine, which has been shown to be effective in preventing transplacental CMV transmission, was tested for reactivation during pregnancy. In Hartley strain guinea pigs intraperitoneally given 10(5.5) 50% tissue culture infective doses (TCID50) of low-passage vaccine, 27 (41%) of 66 throat swabs obtained during subsequent pregnancies showed CMV, in contrast to 28 (24%) of 115 throat swabs obtained from nonpregnant control animals. High-passage GPCMV vaccine (approximately 5 X 10(3) TCID50) did not cause acute viremia, detectable generalized infection, or GPCMV reactivation during subsequent pregnancies. Immune pregnant animals and their fetuses were protected against generalized CMV infection when challenged with virulent GPCMV. In contrast, nonimmune pregnant controls developed generalized maternal, placental, and fetal infection. Experimental low-dose, high-passage GPCMV vaccine can protect against transplacental CMV transmission without apparent vaccine reactivation during pregnancy.

Animals↗
PubMed1984

Effect of acyclovir and phosphonoformate on cytomegalovirus infection in guinea pigs.

Adult Hartley guinea pigs infected with guinea pig cytomegalovirus (CMV) develop a mononucleosis syndrome with a brief viremia, splenomegaly, lymphadenopathy, and peripheral lymphocytosis with circulating atypical lymphocytes. The present study used this experimental model to evaluate in vivo the therapeutic efficacy of acyclovir (ACV) and phosphonoformate (PFA) during CMV infection. Guinea pigs were treated with ACV or PFA from day 3 to day 7 postinoculation. The course of the mononucleosis syndrome and the spread of virus in various tissues were similar in drug- and sham-treated infected guinea pigs. Infected animals treated with ACV or PFA developed disseminated CMV disease with severe interstitial pneumonia, whereas sham-treated infected and drug-treated noninfected animals did not. In addition, mortality rates in infected animals treated with ACV were significantly higher than those in sham-treated animals. Furthermore, the normal lymphoproliferative response to CMV infection appeared to be reduced in ACV-treated as compared to sham-treated animals, with fewer peripheral lymphocytes, less lymphoid tissue in the spleen and lymph nodes, and less mononuclear inflammation around the inclusion-containing cells of the liver and salivary gland. These results show that ACV and PFA are not useful in the treatment of CMV infection in guinea pigs but instead may have harmful effects.

Acyclovir↗
PubMed1983

Enhancement of cytomegalovirus infection during pregnancy in guinea pig.

The effects of pregnancy on primary acute and chronic persistent infection with cytomegalovirus (CMV) were examined in the guinea pig model. Pregnant guinea pigs developed a more severe acute CMV infection than did nonpregnant animals. High death rate, pronounced splenomegaly, interstitial pneumonia, and necrosis with inclusions in various tissues were observed only in pregnant animals. Acutely infected pregnant animals also differed from nonpregnant animals by the absence of tissue inflammation and by a delay in the peripheral lymphoproliferative response. During persistent infection, salivary gland virus titers were significantly higher in pregnant animals than in nonpregnant guinea pigs. These results indicate that during acute guinea pig CMV infection, virus clearance and recovery from clinical disease are altered in the pregnant host. Furthermore, enhancement of persistent chronic guinea pig CMV infection occurs in the salivary glands during pregnancy.

Animals↗
PubMed1983

Effect of phosphonoformate on symptomatic genital herpes simplex virus type 2 infection of guinea pigs.

Using a guinea pig model of genital herpes simplex virus (HSV) type 2 infection, phosphonoformate treatment initiated after the onset of symptoms had a therapeutic effect on the outcome of disease. Severity of disease, viral shedding, and HSV-induced cellular changes in vaginal cytology were significantly reduced in drug-treated animals as compared to sham-treated animals, although virus was readily detected in the nervous system of animals from both groups. The percentage of animals harboring latent virus in their dorsal root ganglia was approximately the same in both drug-treated and sham-treated animals. No drug toxicity was found.

Animals↗
PubMed1982

Effect of acyclovir on genital infection with herpes simplex virus types 1 and 2 in the guinea pig.

The pathogenesis of genital infection with three different strains of herpes simplex virus type 1 (HSV-1) and three strains of herpes simplex virus type 2 (HSV-2) was compared in the guinea pig. Strain differences in severity of clinical disease and mortality were noted. HSV-1 strains generally produced milder disease than HSV-2. Both HSV-1 and HSV-2 infections resulted in acute and chronic changes in the cervix. Virus recovery during latent infection was more frequently obtained from the spinal cord in HSV-1-infected animals and from lumbosacral ganglia in HSV-2-infected animals. Systemic treatment with acyclovir, after the onset of clinical disease, had minimal, if any, effect on genital infection with HSV-1 (NYU-78), but similar treatment of HSV-2 (WT-186) infection resulted in decreased lesion scores, paralysis, and mortality during acute infection. A reduction in virus isolations from lumbosacral ganglia was noted during both acute and latent infection with HSV-2 (WT-186) in the acyclovir-treated groups.

Acyclovir↗
PubMed1982

Effects of vaccination on cytomegalovirus-associated interstitial pneumonia in strain 2 guinea pigs.

The pathogenesis and prevention of generalized infection and interstitial pneumonia due to cytomegalovirus (CMV) in inbred strain 2 guinea pigs were investigated. Eighteen animals inoculated with approximately 10(7) 50% tissue culture infective doses of virulent salivary gland-passaged guinea pig CMV (GPCMV-SG) developed generalized, viremic CMV infections, and 44% of the animals died. Most (68%) cocultivated tissues showed CMV infection, including lungs, which demonstrated severe bilateral interstitial pneumonia. Guinea pigs inoculated with live tissue culture-passaged GPCMV (GPCMV-TC) vaccine developed mild, nonlethal, generalized CMV infections and minimal histopathologic changes in infected tissues, including lungs. After challenge of 19 GPCMV-TC-vaccinated animals with GPCMV-SG, viremia was detectable in two (11%); CMV was detected in 15% of cocultivated tissues and rarely in lungs. Although vaccinated animals showed histologic evidence of interstitial pneumonia after challenge, none died. Strain 2 guinea pigs are useful for studies of pathogenesis and prevention of generalized CMV infection, particularly CMV-associated interstitial pneumonia.

Animals↗
PubMed1982

Effect of acyclovir on genital herpes in guinea pigs.

The chemotherapeutic efficacy of acyclovir was evaluated in guniea pigs that were inoculated intravaginally with herpes simplex virus type 2 (HSV-2). Acyclovir was administered systemically (50 mg/kg of body weight per day ip) beginning three days after inoculation and continuing for 10-11 days. Treatment with acyclovir reduced the incidence of paralysis of the hind limbs, mortality, and the severity and duration of genital lesions but had little effect on the excretion of virus from the genital tract. Recovery of HSV-2 from neural tissues of infected animals during latent infection was less frequent in acyclovir-treated animals than in untreated ones. These data suggest that acyclovir may be a promising drug for altering the severity of clinical genital herpes in humans during acute infection and reducing the incidence of viral latency following primary infection.

Acyclovir↗
PubMed1982

Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs.

The virologic and histologic characteristics of congenital cytomegalovirus infection (CMV) were defined in 65 neonatal guinea pigs born from 27 mothers infected pregnancy. Infectious virus or tissue lesions were present in 54% of the neonates tested. Guinea pig CMV was detected most often in the salivary glands (72%) and spleen (33%) of infected guinea pigs. Less frequently, virus was also detected in the brain, lung, pancreas and liver. Tissue lesions were most frequently observed in the brain and kidney, but also occurred in the salivary glands, liver, pancreas, thymus and spleen. The histopathology was identical to that observed in infants with congenital CMV infection. Infectious virus and histopathology were present in newborn guinea pigs born from mothers infected at any time during gestation. Newborns from mothers infected during early stages of gestation and virus present most frequently in the salivary glands, whereas offspring of mothers infected in late pregnancy had virus present in several tissues. Acute maternal guinea pig CMV infection produced generalized CMV infection of the offspring which was followed by persistent infection in neonatal salivary glands. Lesions remained present in several neonatal tissues including the brain. The long term consequences of such lesions in affected guinea pigs remain to be determined. The results of the study emphasize the similarities between human congenital CMV infection and congenital guinea pig CMV infection, thereby underlining the utility of this animal model as a means of understanding human congenital CMV infection.

Animals↗
PubMed1981

Cytomegalovirus-induced mononucleosis in guinea pigs.

The effects of cytomegalovirus (CMV) infection on hematopoietic and lymphoid tissues were studied in guinea pigs. Blood parameters, histopathology, and virus distribution in the bone marrow, spleen, lymph nodes, and thymus were assessed during primary nonlethal acute and chronic guinea pig CMV infection. Transient hematological changes comparable to those seen in human CMV mononucleosis were observed during acute infection. These included anemia and leukocytosis with atypical lymphocytes. Splenomegaly and stimulation of spleen and lymph node T- and B-cell areas were also noted. These changes occurred at the peak of virus recovery from all tissues tested, as well as from macrophages and B- and T- cell-enriched spleen subpopulations. Virus was cleared rapidly from blood and bone marrow; blood counts, spleen size, and histology returned to normal within 1 month after virus inoculation. However, guinea pigs failed to eliminate the virus completely from lymphoid tissues, since virus persisted in splenic macrophage and B-lymphocyte-enriched populations during chronic infection. The data suggest that CMV-infected mononuclear cells play a role in the establishment of generalized acute infection and virus persistence.

Animals↗