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Biomedical subjects

G A Cabral

Publications and source records attributed to G A Cabral.

At least 55 records · Page 3Linked to original sources
PubMed1986

Delta 9-tetrahydrocannabinol decreases alpha/beta interferon response to herpes simplex virus type 2 in the B6C3F1 mouse.

This study was undertaken to determine the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on polyinosinic:polycytidylic acid [poly(I):poly(C)]-induced, and on herpes simplex virus type 2 (HSV-2)-induced, alpha/beta interferon in the B6C3F1 mouse. Animals were administered delta 9-THC, or the diluent, intraperitoneally for 4 consecutive days or at various time intervals prior to administration of the interferon inducer. Poly(I):poly(C) or HSV-2 was injected intravenously on Day 4. Animals receiving poly(I):poly(C) and treated with delta 9-THC at doses ranging from 5 to 100 mg/kg exhibited significantly lower titers of interferon than mice given poly(I):poly(C) and the diluent. Diminished interferon titers occurred in HSV-2-infected animals treated with delta 9-THC in doses exceeding 15 mg/kg when compared to virus-infected animals given the diluent. This suppression of early interferon persisted through 24 hr.

Animals↗
PubMed1986

Effect of delta 9-tetrahydrocannabinol on herpes simplex virus type 2 vaginal infection in the guinea pig.

The present investigation was undertaken to determine whether delta 9-tetrahydrocannabinol (delta 9-THC) decreases host resistance to herpes simplex virus type 2 vaginal infection in the guinea pig. The guinea pig was selected as the host since it has been shown to express a spectrum of primary herpes genitalis which is similar to that in humans. Animals were administered delta 9-THC or vehicle intraperitoneally on Days 1-4, 8-11, and 15-18. Herpes simplex virus was introduced intravaginally on Day 2. Host resistance to virus infection was assessed by comparing frequency and severity of lesions, virus shedding, and animal mortalities. Virus-infected animals treated with drug at doses of 4 and 10 mg/kg exhibited significantly greater severity of genital disease during the 30-day period of study when compared to virus-inoculated vehicle controls. A direct relationship was noted between dose of delta 9-THC and cumulative mortalities on Day 14 following primary infection. These results indicate that delta 9-THC decreases host resistance to herpes simplex virus type 2 vaginal infection in the guinea pig.

Animals↗
PubMed1985

delta-9-Tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in the B6C3F1 mouse.

The effect of delta-9-tetrahydrocannabinol (Delta-9-THC) on host resistance to herpes simplex virus type 2 (HSV-2) vaginal infection in the B6C3F1 mouse was determined. Animals were given Delta-9-THC or vehicle on days -1 to 2, or cyclophosphamide on day -1 or on days -1 to 2. HSV-2 was introduced intravaginally on day 0. Host resistance to virus infection was assessed by comparing frequency and severity of lesions, virus shedding and mortalities. Replicate groups of animals were bled on days 5, 8, 10, 14 and 21 post-viral inoculation to allow for screening for viraemia and for definition of the effect of Delta-9-THC on the humoral response. Animals were also employed for determination of delayed hypersensitivity responses (DHR). Virus-infected animals treated with 100 mg/kg Delta-9-THC exhibited greater severity of herpes genitalis, higher mortalities and higher mean titres of virus shed from the vagina. Suppression of the humoral response to HSV-2 occurred in animals treated with this dose of drug when compared to virus-infected vehicle controls. A delay in the onset of the DHR to HSV-2 was observed in animals receiving 100 mg/kg Delta-9-THC when compared with those receiving vehicle. These results indicate that Delta-9-THC decreases host resistance to HSV-2 vaginal infection in the B6C3F1 mouse. This decreased resistance is associated with suppression of the immune response to primary infection with HSV-2.

Animals↗
PubMed1983

A herpesvirus antigen in human premalignant and malignant cervical biopsies and explants.

Cervical biopsies and explant cultures from patients with squamous metaplasia, various grades of dysplasia, carcinoma in situ (CIS), and invasive squamous cell carcinoma were screened for VP143, an early nonstructural polypeptide of herpes simplex virus type 2 (HSV-2), VP143 was identified in 31% of biopsies exhibiting severe dysplasia, 29% with CIS, and 41% with invasive squamous cell carcinoma. Similar results were obtained when explants derived from these biopsies were examined for VP143. The expression of the protein persisted in passaged subcultures in four of five invasive carcinomas which originally contained VP143. Staining for VP157, the major capsid protein of HSV-2, was absent. Furthermore, virus structures were not seen by electron microscopy and infectious virus was not isolated from cell cultures inoculated with biopsy extracts. These results suggest that VP143 was expressed in the premalignant and malignant cervical cells in the absence of productive viral infection. Thus, a fragment of the HSV-2 genome was retained within the cells, the expression of which resulted in the production of VP143.

Antigens, Viral↗
PubMed1982

Expression of herpes simplex virus type 2 antigens in premalignant and malignant human vulvar cells.

Vulvar biopsies and explants from patients with vulvitis, hyperkeratosis, condyloma acuminatum, severe dysplasia, and squamous cell carcinoma were screened for herpes simplex virus type 2 (HSV-2) antigens. Immunoperoxidase staining for VP143, an early nonstructural polypeptide of HSV-2, was identified within three biopsies exhibiting severe dysplasia, three of seven with carcinoma in situ, and one of three with invasive squamous cell carcinoma. Similar staining for VP143 was observed in derived explants. Staining for VP119, the major envelope glycoproteins of HSV-2, was identified within tissues which were positive for VP143. Both proteins were expressed in the absence of staining for virus capsid proteins, detection of virus structures by electron microscopy, and isolation of infectious virus by co-cultivation, indicating that only a fragment of the virus genome was expressed. Neither VP143 nor VP119 was identified in biopsies exhibiting vulvitis, hyperkeratosis, or condyloma acuminatum. These data indicate a close relationship between HSV-2 and vulvar neoplasia.

Adult↗
PubMed1981

Microscopic examination of the intracellular fate of infectious herpes simplex virus DNA.

The intracellular fate of 3H-labeled exogenous herpes simplex virus type 2 DNA following the exposure of recipient cells to selected DNA facilitators and the ultrastructural changes which ensued in transfected cultures were examined. In most cases, electron microscopic radioautography demonstrated that exogenous DNA reached the nucleus within 1 h postinoculation. At later time periods, enlargement of nuclei and margination of chromatin were noted. Cells treated with polyornithine differed significantly from those treated with other facilitators in that large cytoplasmic accumulations of labeled material associated with electron-dense, membrane-bound bodies persisted after 1 h postinoculation. In contrast, labeled DNA released by intact virions was detected in the nucleus as early as 20 min postinfection (p.i.), and progeny virus was evident by 8 h p.i. These results suggest that the efficiency of each facilitator is related to the rapidity with which exogenous DNA penetrates the recipient cell, traverses the cytoplasm, and the amount of DNA which is finally associated with the nuclear compartment.

Alkaloids↗
PubMed1981

Nuclear changes in hepatocytes of patients with non-A, non-B hepatitis.

Experimental non-A, non-B hepatitis infection has been shown to produce two distinct ultrastructural changes in chimpanzees: intranuclear particles and intracytoplasmic tubular structures. We report our observations of intranuclear particles in humans with acute non-A, non-B hepatitis. These particles appear to be specific for at least one type of non-A, non-B hepatitis.

Adult↗
PubMed1980

Ultrastructural characterization of an early, nonstructural polypeptide of herpes simplex virus type 1.

An immunoperoxidase procedure was employed to study the expression of a large-molecular-weight, virus-induced polypeptide (VP175; molecular weight, 175,000) at the light and electron microscopic levels in Vero cells infected with herpes simplex virus type 1 or with tsB2, a DNA-negative, temperature-sensitive mutant of herpes simplex virus type 1. In cells infected with herpes simplex virus type 1 and in cells infected with tsB2 at the permissive temperature (34 degrees C), VP175 was found within the nucleus. The protein was detected as early as 2 h postinfection and, by 3 h postinfection, was generally distributed in a marginated pattern contiguous with, and extending from, the inner lamella of the nuclear membrane. At 6 h postinfection, protein accumulations were dispersed throughout the nucleus, and, by 9 h postinfection, these accumulations tended to be localized in a marginated pattern near the nuclear membrane. It was also noted that, at 9 h postinfection, under permissive conditions, VP175 was not found in association with nucleocapsids or enveloped particles. In contrast, in cells infected with tsB2 at the nonpermissive temperature (39 degrees C) and harvested at 6 or 9 h postinfection, accumulations of VP175 were identified not only within the nucleus, but also within the cytoplasm in the form of annular or globular aggregates. These aggregates consisted of a granular matrix and were not bound by membranes.

Animals↗
PubMed1978

Cellular and humoral immunity in guinea pigs to two major polypeptides derived from hepatitis B surface antigen.

Guinea pigs immunized with hepatitis B surface antigen (HBsAg), types adw, adr and ayw, and with two major polypeptides derived from HBsAg/adw developed cell-mediated immunity as determined by the macrophage migration inhibition assay. Peritoneal exudate cells from animals immunized with a 22000- or a 25000-mol. wt. polypeptide derived from HBsAg/adw showed significant migration inhibition after challenge with either polypeptide or with purified HBsAg. Significant inhibition of macrophage migration was not observed when polypeptide-sensitized cells were challenged with normal human serum or with normal human liver extract. Similarly, a cell-mediated immune response was not observed in peritoneal exudate cells from animals sensitized to normal human serum or normal human liver extract which were challenged with either of the polypeptides. The humoral immune response to either of the polypeptides, as measured by radioimmunoassay, was substantially lower than that observed in animals immunized with intact particles. This apparent difference between cellular and humoral responses suggests that the macrophage migration assay is a sensitive indicator of the immunogenicity of the smaller mol. wt. HBsAg-derived polypeptides in guinea pigs.

Animals↗
PubMed1978

Coxsackievirus aggregates in muscle cells of a polymyositis patient.

Muscle biopsy specimens of a patient with polymyositis showed crystalline structures resembling picornavirus aggregates within muscle cells. The patient's serum reacted in an indirect immunofluorescence assay with autologous muscle cells. A strongly positive immunofluorescence staining was also noted when a section of muscle tissue was reacted with coxsackievirus A9 antiserum, and a weakly positive reaction was noted with coxsackievirus B2 antiserum. No staining was observed after treatment with antiserum to poliovirus type 1 or echovirus types 11 and 22.

Aged↗
PubMed1977

Experimental carcinoma of liver in macaque monkeys exposed to diethylnitrosamine and hepatitis B virus.

The effects of treatments with diethylnitrosamine (DENA) and hepatitis B virus (HBV) on macaque monkeys were investigated by virus serology and by light and electron microscopy. The experimental groups comprised 43 newborn or juvenile cynomolgus and rhesus monkeys of both sexes. HBV neither had a carcinogenic effect nor increased the oncogenic effect of DENA. However, HBV given to juvenile primates before treatment with DENA resulted in subsequent gross and microscopic alterations consistent with mild hepatitis and postnecrotic cirrhosis; multifocal liver carcinoma apparently developed within these cirrhotic nodules. The pathologic findings in the experimental animals were strikingly similar to those observed in liver cancer patients.

Animals↗
PubMed1976

Electron microscope studies of temperature-sensitive mutants of herpes simplex virus type 2.

Nine temperature-sensitive mutants of herpes simplex virus type 2 representing eight complementation groups were assigned to two classes as a consequence of the virion forms and virus-specific cellular alterations observed in thin sections of mutant-infected human embryonic lung cells grown at the nonpermissive temperature. Mutants in class A, one DNA- and one DNA +, failed to synthesize detectable virus particles. Mutants in class B, 4DNA- and 3DNA+, produced moderate to large numbers of empty nucleocapsids. Dense-cored nucleocapsids were not observed in thin sections of cells infected with any of the nine mutants at this temperature. Virus-specific cellular alterations consisted primarily of margination of chromating and nulcear membrane thickening and duplication.

Capsid↗
PubMed1975

Cell-mediated immunity in guinea pigs to subunits derived from hepatitis B surface antigen.

Guinea pigs immunized wit- hepatitis B surface antigen (HBSAg), types adw and ayw, and with two polypeptides (400,000 and 24,000 molecular weight) developed cell-mediated immunity (CMI), as determined by radioimmunoassay. Peritoneal exudate (PE) cells from guinea pigs immunized with the 40,000-molecular-weight polypeptide migrated poorly (30 to 88% inhibition) after challenge with the immunizing subunit or with purified HBSAg, type gdw or ayw. Response of the same PE cells to the 24,000-molecular-weight subunit was significantly reduced. Similar but less striking evidence for CMI was observed was PE cells derived from guinea pigs inoculated with purified type-specific HBSAg or with the 24,000-molecular-weight polypeptide. Humoral responses were predictable and showed a reasonable degree of correlation with the CMI response. PE cells from control animals inoculated with normal human serum or polyacrylamide gel were not inhibited after challenge with purified preparations of HBSAg or with the 400,000-molecular-weight polypeptide, but did show CMI with their respective immunogens. In addition, PE cells from guinea pigs inoculated with normal human serum were inhibited from migrating after challenge with the 24,000-molecular-weight subunit, suggesting that the latter may contain an antigenic determinant related to a human serum protein.

Animals↗
PubMed1975

Humoral and cellular immunity in guinea pigs to polypeptides derived from HBsAg-containing particles.

Recent studies in this laboratory have shown that purified HBsAg contains at least 7-9 polypeptide subunits ranging in molecular weight (MW) from 18,000 to 120,000; at least three of these are associated with carbohydrates. In addition, two glycosphingolipids have been extracted which are structurally similar to the blood group antigenic substance. The glycoproteins and glycolipids are of particular interest since it has been reported that carbohydrate is associated with the antigenic activity of HBsAg. Antisera to these subunits have been produced in guinea pigs. These results stimulated further 'in vivo' investigations into the possible development of a subunit vaccine which would exclude genes of a viral or cellular nature and would not be infectious. Guinea pigs were immunized with HBsAg, subtypes adw and ayw, and with two polypeptides (40,000 MW and 24,000 MW) in complete Freund's adjuvant. Control animals were inoculated with normal human serum or with polyacrylamide gel. Animals were boostered on day 14 and tested on day 30 for the development of cell-mediated immunity (CMI) by the macrophage inhibition assay, and for humoral immunity by PHA and RIA. Migration of peritoneal exudate (PE) cells was inhibited 30-88% in guinea pigs immunized with the 40,000-MW polypeptide when challenged with purified HGsAg, subtype adw or ayw, or with the 40,000-MW preparation, but the results were inconclusive with the 24,000-MW subunit. Similar evidence of CMI was observed with PE cells derived from guinea pigs inoculated with purified subtype-specific HBsAg or with the 24,000-MW polypeptide. Humoral responses were predictable, and showed a reasonable degree of correlation with the CMI response. Control animals failed to respond to challenge with purified preparations of HBsAg or the 40,000-MW polypeptide, but did show CMI with their respective immunogens and - in the case of guinea pigs inoculated with normal human serum - with the 24,000-MW subunit, suggesting that the latter may contain an antigenic determinant related to a human serum protein.

Animals↗