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Biomedical subjects

A J Pinto

Publications and source records attributed to A J Pinto.

10 recordsLinked to original sources
PubMed1993

Characterization of murine Caraparu Bunyavirus liver infection and immunomodulator-mediated antiviral protection.

A rapid, peripheral disease model utilizing the Bunyavirus, Caraparu, was established in mice for the evaluation of antiviral therapy with immunomodulators. 4-6-week-old B6C3F1 female mice, inoculated intraperitoneally with virus, developed coagulative liver necrosis and died between 4-6 days after infection. This Caraparu disease model was relatively resistant to treatment with immunomodulators, such as ABMP, Ampligen, alpha-interferon (IFN-alpha) or beta-interferon (IFN-beta). However, a significant increase in median survival time (MST) was consistently observed upon treatment with gamma-interferon (IFN-gamma). The nucleoside analog--ribavirin--was highly effective against Caraparu virus in repeated treatment schedules begun on either day -1, day 0, or day +1 of infection. Ribavirin gave little protection when initiation of treatment was delayed until day +2. However, combined treatment with IFN-gamma, starting on day 0 and ribavirin starting on day +2, significantly reduced mortality.

Adjuvants, Immunologic↗
PubMed1993

Evaluation of pulmonary systemic blood flow using ECG gated acquisition.

We propose a functional parametric analysis method using ECG-gated 99mTc-labeled red blood cell (RBC) imaging for detection and characterization of periodic variations in local blood activity in the lungs during cardiac cycle. We validated in animal experiments that such count variations correlate with cyclical pulmonary blood flow and may be used for evaluation of systemic-to-pulmonary shunts. Clinical studies were performed in 48 patients. After labeling the RBC pool with 99mTc, ECG-gated gamma camera images of both lung fields were acquired and processed to obtain Fourier transforms of time/activity functions in selected regions. The first harmonic parametric images of amplitude and phase were derived. There was an excellent correlation (r = 0.92) between activity variations and pulsatile flow measured by our method with that obtained by the thermodilution method in dog experiments (n = 10) after implantation of a systemic-to-pulmonary shunt. Patient studies showed the technique to be sensitive in detecting and quantifying abnormal systemic-to-pulmonary blood flow. Lung pulsatile flow can thus be noninvasively measured from functional parametric phase and amplitude images; the technique may be useful for detecting and quantifying abnormal systemic-to-pulmonary blood flow in man.

Animals↗
PubMed1992

Biologic response modifiers as antivirals in immunosuppressed hosts.

A wide variety of immunomodulators/biologic response modifiers (BRM) have been demonstrated to provide broad spectrum antiviral activity against both RNA and DNA viruses in several animal species. Dramatic decreases in mortality, reduced virus titers in tissues, and reduced histopathology can be produced. The antivirally effective agents include microbially derived materials, polyanions, cytokines, and chemically diverse small molecular weight chemicals. Antiviral efficacy with BRM treatment has been shown in numerous kinds of immunosuppression, emphasizing the potential for BRM treatment in immunocompromised patients. The greatest protective effects are observed with prophylactic or early therapeutic treatment. BRMs act indirectly, most likely by activating cells and/or inducing antiviral mediators early in the course of viral pathogenesis. In general, viral specific immune responses in BRM-treated and infected mice are absent or similar to those in untreated mice. Because BRMs are pleiotropic in their immunomodulatory effects, it has been difficult to establish whether one cell type or mediator is critical for the broad spectrum antiviral activity. Interferon appears to be critical for some small molecular weight synthetic compounds, but does not appear to explain all the antiviral activity of certain large molecular weight polyanions. Whether there is a unified antiviral mechanism among different BRMs remains to be determined.

Adjuvants, Immunologic↗
PubMed1991

Selective depletion of liver and splenic macrophages using liposomes encapsulating the drug dichloromethylene diphosphonate: effects on antimicrobial resistance.

The current results provide direct evidence for a role of tissue macrophages (M phi) in natural immunity and support the use of immunomodulators to enhance antiviral resistance in immunocompromised individuals. In this study, macrophages (M phi) in the spleen and liver were eliminated by intravenous (i.v.) injection of the drug dichloromethylene diphosphonate (DMDP) encapsulated in liposomes. The effect of this depletion system on peritoneal M phi, peripheral blood leukocytes, splenic natural killer (NK) activity, and natural and immunomodulator-induced host resistance was then assessed. Barrier-maintained CD-1 female mice were inoculated i.v. either with DMDP liposomes, free liposomes (containing no DMDP), or saline on day -2 or on days -3 and -1 before cell population analysis or infection. Single or double treatment with DMDP liposomes had no effect on peritoneal M phi as indicated by no changes in total number, differential counts, or ectoenzyme patterns. Double treatment with DMDP liposomes caused a marked leukocytosis in blood, primarily of lymphocytes and polymorphonuclear leukocytes (PMN), and a transient depression of spontaneous and interferon-inducible splenic NK activity. The effects on host resistance to i.v. infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) indicated that i.v. treatment with DMDP liposomes significantly reduced natural resistance to these microorganisms as evidenced by increased mortality and decreased median survival time. When DMDP liposomes-treated mice were given the immunomodulator maleic anhydride divinyl ether copolymer (MVE-2) intraperitoneally the day before infection with HSV-2, the immunosuppressive effect of DMDP liposomes treatment was significantly reversed.

Adjuvants, Immunologic↗
PubMed1991

Ventilation and perfusion display in a single image.

A new method of ventilation and perfusion display onto a single image is presented. From the data on regions of interest of the lungs, three-dimensional histograms are created, containing as parameters X and Y for the position of the pixels, Z for the perfusion and colour for local ventilation. The perfusion value is supplied by sets of curves having Z proportional to the local perfusion count rate. Ventilation modulates colour. Four perspective views of the histogram are simultaneously displayed to allow visualization of the entire organ. Information about the normal ranges for both ventilation and perfusion is also provided in the histograms.

Adult↗
PubMed1991

Sequential determination of immunocytochemical estrogen receptor and nuclear DNA content in fine needle biopsies from breast carcinoma.

The application of fine needle biopsy as a tool for early detection of breast cancer is becoming extensive, therefore parameters reported to be associated with prognosis should be standardized in this material. We propose the sequential determination of estrogen receptor (ER) status and DNA ploidy on the same smear obtained from a fine needle biopsy of a breast carcinoma, since both parameters seem to reflect properties associated with tumor behaviour and biological aggressiveness. Fifty fine-needle biopsies were investigated for presence of ER by the monoclonal antibody D75 followed by DNA content quantification using Feulgen-DNA cytophotometry. Overall, 66% of the tumors showed immunoreactivity for ER and 66% were classified as aneuploid. Forty-one percent of the aneuploid tumors were negative for ER, while only 7% of the diploid tumors showed no immunoreaction (p less than 0.05). The significant association between absence of immunocytochemical ER and DNA aneuploidy on the same fine-needle smear is consistent with data obtained through other methods previously reported using much larger tissue samples.

Adult↗
PubMed1990

Comparative therapeutic efficacy of recombinant interferons-alpha, -beta, and -gamma against alphatogavirus, bunyavirus, flavivirus, and herpesvirus infections.

Recombinant (r) preparations of interferons (IFN)-alpha, -beta, and -gamma were shown to protect mice against experimental virus infections with herpes simplex virus type 2 (HSV-2), and with three RNA-containing viruses from different families: Banzi, a flavivirus; Semliki Forest virus (SFV), an alphatogavirus; and Caraparu, a bunyavirus. The antiviral effects of the three different types of IFN were different with each virus. HSV-2 was the most sensitive virus, followed by SFV. Against Banzi virus, IFN-gamma was only effective when given both before and after infection. Against Caraparu virus, only IFN-gamma had a significant effect. These results suggest that IFN therapy might be valuable in human infections with these viruses, but that the correct choice of IFN and dose regimen is likely to be important.

Alphavirus↗
PubMed1988

Comparative study of various immunomodulators for macrophage and natural killer cell activation and antiviral efficacy against exotic RNA viruses.

Several immunomodulators were compared for immunomodulatory and antiviral activity in B6C3F1 female mice. Our results demonstrate that murine recombinant gamma interferon (rIFN-G), human recombinant alpha A/D interferon (rIFN-A), ampligen (a polyribonucleotide) and CL246,738 modulate nonspecific immunity and are effective antiviral agents in vivo. Administration of each of these agents 1 day before cell harvest induced high levels of splenic natural killer (NK) cell activity against YAC-1 target cells. rIFN-G was also a potent activator of peritoneal macrophages (M phi), as evidenced by high levels of antitumor activity and changes in ectoenzyme phenotype that is characteristic of tumoricidal M phi. rIFN-A, ampligen and CL246,738 induced moderate to low levels of M phi activation by these criteria. In vivo protection experiments showed that repeated therapeutic treatment with rIFN-A protected mice against i.p. infection with Venezuelan equine encephalitis (an alpha togavirus, VEE), Banzi (a flavivirus) and herpes simplex virus type 2 (HSV-2). Similar treatment with rIFN-G was effective against VEE and HSV-2, but ineffective against Banzi virus. A single prophylactic i.p. dose of ampligen 1 day before virus challenge was very effective against Banzi virus, moderately effective against HSV-2, and ineffective against VEE and Caraparu (a bunyavirus) infection. A single prophylactic oral dose of CL246,738 provided almost complete protection of mice against VEE, Banzi, and HSV-2, and also increased the mean survival time for Caraparu infected mice. Collectively, these results indicate that rIFN-A, r-IFN-G, ampligen and CL246,738 may be useful in prophylactic or early therapeutic treatment of several serious virus infections. Since these agents stimulate NK cells and M phi, their antiviral activity may result, in part, from the alterations they induce in the natural immune system.

Adjuvants, Immunologic↗
PubMedDate not supplied

Intrinsic resistance to herpes simplex virus type 1 infection in liver Kupffer cells and peritoneal macrophages from normal and immunomodulator-treated mice.

In contrast with other macrophage (MO) populations, there is little information on the antiviral resistance in vitro of isolated liver MO (Kupffer cells, KC). We have demonstrated that the KC exhibits marked intrinsic resistance to infection in vitro with herpes simplex virus type 1 (HSV-1). Liver and peritoneal MO (PMO) were harvested from untreated mice (naive), from mice treated with drug vehicle, or from mice treated with either a synthetic nonspecific immunomodulator, maleic anhydride divinyl ether copolymer (MVE-2), or with MO colony-stimulating factor-1 (CSF-1). The studies revealed that resident KC, isolated by two different methods, are equally as nonpermissive for infection with HSV-1 as are resident PMO. When infected with HSV-1, resident KC showed no cytopathic effect, and no infectious virus was produced. Intravenous (i.v.) treatment of mice with MVE-2 (50 mg/kg 3 days before cell harvest) increased the number of KC recovered. However, neither i.v. treatment with MVE-2 nor CSF-1 (20,000 U daily for 4 days) had any pronounced effect on the permissiveness of KC or PMO to infection with HSV-1. These data support a role for KC in host antiviral resistance, and indicate that KC intrinsic antiviral resistance is maintained during immunotherapy with MVE-2 or CSF-1.

Adjuvants, Immunologic↗