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Biomedical subjects

C R Rinaldo

Publications and source records attributed to C R Rinaldo.

At least 127 records · Page 7Linked to original sources

Human polymorphonuclear leukocyte interaction with cyclosporine A.

The effects of cyclosporin A (cyA) on human polymorphonuclear leukocyte function, including phagocytosis, its associated metabolic burst, bacterial killing, and chemotaxis, were evaluated. Both Pseudomonas aeruginosa and Staphylococcus aureus were used as test particles. Polymorphonuclear leukocytes incubated in 10 and 50 micrograms of cyA per ml behaved normally with respect to phagocytosis and hexose monophosphate shunt activity at both high (10:1) and low (2:1) S. aureus/leukocyte ratios. With a small bacterial inoculum, killing of S. aureus was slightly impaired at early times only in the presence of 50 micrograms of cyA per ml. Phagocytosis and killing of P. aeruginosa with both large and small bacterial inocula were unaffected by cyA. Chemotaxis was within normal limits under all conditions. In addition, polymorphonuclear leukocytes from four renal transplant recipients receiving both cyA and prednisone demonstrated normal metabolic bursts and bacterial killing with both small and large inocula of S. aureus.

Blood Bactericidal Activity↗

Alteration of immunoregulatory mechanisms during cytomegalovirus mononucleosis: effect of in vitro culture on lymphocyte blastogenesis to viral antigens.

Immunoregulation of lymphocyte blastogenesis was studied in 13 patients with acute-phase cytomegalovirus (CMV) mononucleosis and 9 of these patients during the convalescent phase of the illness. Peripheral blood mononuclear leukocytes from acute-phase patients displayed depressed uptake of [3H-]thymidine in response to the lectin-mitogen concanavalin A (Con A) and immune-specific viral antigens (CMV, herpes simplex virus (HSV), mumps virus) compared with convalescent patients or normal donors. Removal of plastic-adherent cells from the patients' samples resulted in further depression of lymphocyte blastogenesis to Con A and CMV and HSV antigens, suggesting a helper function for the predominantly monocytic, adherent cell population in this response. Preliminary culture of mononuclear leukocytes from acute-phase patients for 18 hr at 37 degrees C resulted in significantly enhanced blastogenesis to Con A. In sharp contrast, lymphocyte blastogenesis to viral antigens was not significantly enhanced after preculture. These results suggest that different mechanisms are operative in immunoregulation of lymphocyte recognition responses to the polyclonal activator Con A and immune-specific viral antigens during human CMV infection.

Acute Disease↗

Lymphocyte subsets and natural killer cell responses during cytomegalovirus mononucleosis.

Cell-mediated immunity in seven patients with cytomegalovirus mononucleosis was assessed by monoclonal antibody to lymphocyte subsets, lymphocyte blastogenesis, and natural killer cell activity. The patients had decreased ratios of helper (Leu 3a) to suppressor-cytotoxic (Leu 2a) T cells as compared with normal donors. Leu 2a+ T cells from the patients were uniquely sensitive to overnight culturing, which resulted in a 2.6-fold increase in the helper/suppressor cell ratio and the appearance of an unusual third Leu 1+ 2a- 3a- T cell subset. This correlated directly with enhanced blastogenesis to concanavalin A after preculture. Base-line and interferon-boosted natural killer cell responses versus K562 cell targets during cytomegalovirus mononucleosis did not differ from those of normal donors. This suggests that certain cellular immune functions are depressed during cytomegalovirus mononucleosis in correlation with the emergence of a culture-sensitive subset of suppressor T cells. In contrast, cytotoxic lymphocytes appear to function normally and may aid in the resolution of the illness.

Adult↗

Natural killer cell activity in renal transplant recipients receiving cyclosporine.

Normal subjects (n = 11) had a mean circulating natural killer (NK) cell activity of 188 lytic units per 10(7) peripheral mononuclear blood leukocytes. This activity was significantly enhanced by in vitro incubation with 500 U of alpha-interferon (+207 lytic units). The mean NK activity of renal transplant recipients on azathioprine (n = 17) or on cyclosporine (n = 17) studied at various times after transplantation was significantly decreased, as was the ability of interferon to enhance NK activity. In the cyclosporine group, interferon could not enhance NK titers 1 to 6 weeks after transplantation when the patients were on the highest doses of cyclosporine (mean, 1,002 mg/day) or when they were viremic for cytomegalovirus. After 18 weeks, when the patients received 546 mg/day or when viremia was no longer detected, the ability of interferon to enhance NK activity was more normal. Cyclosporine and cytomegalovirus infection may have a greater effect on the action of interferon on NK activity than on the NK titer per se. This defect may diminish the reserve of NK cells and contribute to post-transplant immunosuppression.

Adult↗

Characterization of herpes simplex virus persistence in a human T lymphoblastoid cell line.

Persistent, dynamic-state infection with herpes simplex virus (HSV) type 1 has been maintained in human T lymphoblastoid (CEM) cells for many months after initial infection with the wild-type virus (HSV0) (input virus/cell multiplicity of 1.0). Persistently infected cells grew as well as uninfected cells, except during occasional periods of crisis (increased viral replication and cytopathic effect). Cells could survive the crisis when they were maintained for twice the usual time interval (8 to 10 rather than 4 to 5 days) before subculture. Interferon was not detectable in the cultures. HSV0 was compared with HSVp1, a small plaque-forming isolate from persistently infected CEM cells. Primary infection of CEM cells with HSV0 at a low input multiplicity (0.01) led to abortive replication, whereas infection with HSVp1 at the same multiplicity resulted in either rapidly lytic or persistent infection depending upon the time interval of subculture. Approximately 55% of plaque-purified clones of HSVp1, as compared with only 5% of HSV0 clones, displayed temperature-sensitive growth in Vero cells. Defective interfering virus was not detectable in uncloned HSVp1 by interference assay. Persistently infected cultures "cured" by treatment with HSV antiserum or incubation at 39 degrees C were resistant to reinfection with HSV but permissive for vesicular stomatitis virus replication, suggesting that these treatments modulated a shift from the dynamic-state of the static-state, latent infection. These studies provide a model for characterization of HSV persistence and latency in a highly differentiated human cell line.

Antibodies, Viral↗

Mechanisms of immunosuppression in cytomegaloviral mononucleosis.

During acute cytomegaloviral (CMV) mononucleosis, mononuclear leukocytes displayed diminished responsiveness to certain mitogens. Responses to phytohemagglutinin were normal in patients with community-acquired CMV illness but were reduced in patients with transfusion-associated infection. Both groups were hyporesponsive to pokeweek mitogen and concanavalin A. Cells from convalescent CMV mononucleosis patients responded as well as cells from normal donors to the three mitogens. Preculture of cells from patients with acute CMV mononucleosis for up to seven days before addition of concanavalin A greatly enhanced the blastogenic response to that mitogen. The effect was increased further by depletion of adherent cells after preculture for seven days and could be markedly reduced by the addition of fresh, autologous adherent cells to the precultured nonadherent cells. Suppressor activity was not observed in the serum of patients with acute CMV mononucleosis. These studies suggest that mitogen hyporesponsiveness in CMV mononucleosis may be mediated by suppressor cells included among the plastic-adherent mononuclear leukocyte population.

Adolescent↗

The ultrastructural morphologic features of Pittsburgh pneumonia agent.

The fine structure of "Pittsburgh Pneumonia Agent" (PPA) was studied in infected human lung, guinea pig omentum, yolk sac membrane, Vero cell culture, and after cultivation of the organism on buffered charcoal yeast extract agar. The organism is a prokaryotic cell with the general features of a gram-negative bacillus. PPA is ultrastructurally distinctive because of an unusually thick, electron-dense band present within the periplasmic space adjacent to the outer membrane of the cell wall. This band, presumably a mucopeptide (peptidoglycan) layer, was seen in about 95% of organisms in human lung but less frequently under certain conditions of laboratory infection or cultivation. Future studies are required to determine whether this ultrastructural dimorphism of PPA is related to variation in other properties of this bacterium, eg, gram-variability, acid-fastness, colony morphology, and virulence.

Animals↗

Opportunistic lung infection due to "Pittsburgh Pneumonia Agent".

Eight immunosuppressed patients had pneumonia due to Pittsburgh Pneumonia Agent (PPA), a gram-negative, weakly acid-fast bacterium cultivatable only in embryonated eggs and guinea pigs and distinct from Legionella pneumophila. The diagnosis was established by isolation of the agent from lung or visualization of the organism in lung tissue. The clinical presentations, radiographic abnormalities and pathology were not specific. The most consistent feature associated with the disease was the recent institution of daily high-dose corticosteriod therapy in all patients. Five of the eight patients died despite broad-spectrum antibiotic and antituberculous therapy. Anti-microbial activity against PPA was demonstrated for sulfamethoxazole combined with trimethoprim, for rifampin and for erythromycin with an egg-protection assay. Serologic studies with an indirect fluorescent-antibody technic suggested that seroconversion or high titers may be a sensitive test for PPA disease. PPA appears to be a newly recognized cause of life-threatening bacterial pneumonia in immunosupressed patients.

Adrenal Cortex Hormones↗

New bacterial agent of pneumonia isolated from renal-transplant recipients.

A gram-negative, weakly acid-fast bacillus has been isolated in embryonated eggs and in guineapigs from lung tissue of two renal-transplant recipients with acute purulent pneumonia. Culture of infected lung tissue and subculture of the egg isolate on artificial media, including media for legionnaires' disease bacterium (Legionella pneumophila), failed to produce growth. Ultrastructural analysis showed that the organism is a prokaryote with a cell-wall structure typical of a gram-negative bacillus but different from that of L. pneumophila. In both patients serum antibody to both isolates developed in high titre. In its microbiological, tinctorial, and ultrastructural characteristics this bacterium differs sufficiently from L. pneumophila and other pulmonary pathogens to indicate that it may be a new agent of bacterial pneumonia.

Acute Disease↗

Immune response to herpesvirus antigens in adults with acute cytomegaloviral mononucleosis.

The immune response of eight patients with mononucleosis caused by cytomegalovirus (CMV) was measured early in their illness--when virus was present in their urine and/or blood--and subsequently during convalescence. Levels of CMV-specific antibody rose early in the illness, but the proliferative response of mononuclear cells to CMV antigen did not reach the level characteristic of CMV-immune donors until several months later. The production of interferon by mononuclear cells in response to CMV antigen was also low early in the illness. Although these patients had prior immunity to herpes simplex virus and varicella-zoster virus, their mononuclear cells responded poorly to antigens prepared from these viruses. The proliferative response to these antigens returned to normal in parallel with the development of a normal response to CMV. It is suggested that acute CMV mononucleosis suppresses the proliferative response of human mononuclear cells.

Antibodies, Viral↗

Persistent infection of human lymphoid and myeloid cell lines with herpes simplex virus.

Herpes simplex virus (HSV) type 1 replicated and persisted in human T, B, and myeloid cell lines with different patterns of viral replication and various effects on cell growth. T cell line CEM supported the replication of HSV for over 400 days without detectable differences in cell growth as compared with uninfected cells. HSV persisted in B cell line NC37 and myeloid cell line K562 for up to 222 and 374 days, respectively, but led to a significant decrease in the number of viable cells by 7 weeks of infection. The average number of cells producing infectious virus was very low in these cell lines (range, 0.5 to 2.7+) compared with a larger proportion of cells exhibiting HSV antigens by immunofluorescence (range, 24 to 58%). In contrast, null cell line LAZ 221 failed to replicate HSV even though the viral infection led to a cessation of cell growth.

B-Lymphocytes↗

Resistance of visna virus to interferon.

Visna is a slow infection of sheep caused by a retrovirus. The persistence of virus despite the immune response of the host is best explained by restricted genetic expression of the virus and consequently prolonged periods of residence inside cells. The purpose of this investigation was to determine whether the restriction in genetic expression of visna virus is mediated by interferon. Sheep interferon induced by polyriboinosinic-polyribocytidylic acid in fetal lambs inhibited the growth of herpes simplex virus, vesicular stomatitis virus, and vaccinia virus, but even highly concentrated interferon did not affect the replication of visna virus in sheep choroid plexus cells. The same results were obtained whether the effects of interferon were assessed in single of multiple cycles of growth and when interferon was added at later times in the growth cycle of the virus. This unusual resistance of visna virus to interferon suggests that restriction of viral expression by the host is probably not mediated in this way.

Animals↗

Replication of herpes simplex virus and cytomegalovirus in human leukocytes.

Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection.

Antibodies, Viral↗

Interaction of cytomegalovirus with leukocytes from patients with mononucleosis due to cytomegalovirus.

Cytomegalovirus (CMV) was isolated from hemic cells from seven of seven patients with acute CMV mononucleosis and from one of six patients with mononucleosis during convalescence. CMV was isolated from the mononuclear leukocyte fraction, the polymorphonuclear leukocyte fraction, or both cell fractions. Virus was not detected in washed erythrocytes, plasma, or leukocyte lysates. Mononuclear leukocytes from patients with acute CMV mononucleosis displayed an elevated level of incorporation of [3H]thymidine on the day of donation compared with that in cells from convalescent patients or normal donors. Responses to pokeweed mitogen and concanavalin A were significantly lower in patients with CMV mononucleosis than in normal donors. There were no significant differences among the acute, convalescent, and normal donor groups in response to phytohemagglutinin or in the one-way mixed leukocyte reaction. These findings suggest that in patients with CMV mononucleosis virus infects and may persist within peripheral blood leukocytes and that the lymphocytes of these patients are selectively hyporesponsive to certain mitogens.

Adult↗

Use of interferon in cytomegalovirus infections in man.

Human CMV is relatively sensitive to the antiviral effects of interferon in vitro. No controlled studies of interferon in human CMV infections have been reported. On the basis of case reports published to date, its usefulness in CMV infections of newborns or transplant recipients is unclear. Double-blind, placebo-controlled studies of interferon prophylaxis against CMV infections in renal transplant recipients are currently underway.

Adult↗

Fetal and adult bovine interferon production during bovine viral diarrhea virus infection.

Levels of interferon in adult bovine serum and in fetal bovine serum and tissues were examined during the course of transplacental bovine viral diarrhea virus infection. The cows produced circulating interferon between 2 and 9 days after viral inoculation, with mean peak levels in the serum on day 4. Interferon could be routinely detected in fetal tissues (e.g., thymus, spleen, and kidney) between days 4 and 21 after viral inoculation of the cows at 149 to 150 days of gestation (mid-second trimester) and in fetal serum from day 13 through day 21. Interferon was also detectable in the serum and tissues of fetuses from dams infected at day 95 of gestation (the beginning of the second trimester). In general, no differences were found between the ability of the adult and fetus to produce interferon. Fetal lamb kidney cells were more sensitive to the antiviral effects of bovine interferon than were fetal bovine kidney cells. The antiviral substance from the fetal and adult animals was characterized as interferon by standard criteria.

Age Factors↗