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Biomedical subjects

A Ghaffar

Publications and source records attributed to A Ghaffar.

At least 55 records · Page 3Linked to original sources
PubMed1991

Phosphonylmethoxyalkyl purine and pyrimidine derivatives for treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS.

Murine acquired immunodeficiency syndrome (MAIDS) was induced in C57BL/6 mice following infection with the LP-BM5 retrovirus complex. Infected mice developed splenomegaly, lymphadenopathy and loss of B- and T-cell functions 100 days after virus inoculation. Mice with AIDS were highly susceptible to opportunistic murine cytomegalovirus (MCMV) and herpes simplex virus (HSV-1) infections. The therapeutic activities of two phosphonylmethoxyalkyl derivatives, 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (S)-1-(3-hydroxy-2-phosphonylmethoxy-propyl)cytosine (HPMPC), were evaluated in MAIDS immunosuppressed mice infected with MCMV or HSV-1. MCMV infection resulted in extensive viral replication in lung, liver and spleen and death occurred five to twelve days post-infection. Treatment with either HPMPC or ganciclovir (DHPG) reduced mortality and viral replication in target organs; however, HPMPC was as effective as DHPG at one-fifth the DHPG dose. Moreover, when a single dose (100 mg/kg) of HPMPC was administered 24 h prior to MCMV infection, it suppressed virus replication at seven and 14 days post-infection, thus resulting in a significant prolongation of life. PMEA was effective against opportunistic HSV-1 infections, but appeared to be less effective than HPMPC against MCMV infections. These results indicate that MAIDS can be used as a model for evaluating antivirals in an immunocompromised host, and suggest that both PMEA and HPMPC may be useful in the treatment of opportunistic CMV and HSV-1 infections.

Adenine↗
PubMed1989

Metallothionein immunoreactivity in the liver and kidney of copper injected rats.

Adult male rats were injected intraperitoneally with copper sulphate in physiological saline (3 mg copper/kg body wt). Metallothionein-I (MT-I) levels in liver, kidney, plasma and red blood cells were measured by radioimmunoassay (RIA), prior to the injection and after 7, 16 and 24 h. Copper and zinc levels in liver and kidneys were also monitored. Concentrations of MT-I in liver and kidneys showed a rapid increase and remained elevated for 24 h. Copper concentrations also increased in both tissues but zinc levels remained constant in the kidney and rose only slightly in the liver. MT-I levels increased gradually in plasma but decreased in the red blood cells. Immunochemistry of liver and kidney, using the direct peroxidase technique with antiserum to rat MT-I, revealed an increase in staining in both tissues after copper administration, consistent with the RIA results. The change in distribution of immunoreactive material with time after copper injection indicates a role for MT in the sequestration and excretion of copper in acutely loaded animals.

Animals↗
PubMed1985

Resistance of helper T lymphocytes to cyclophosphamide.

The effect of cyclophosphamide (Cy) on helper T lymphocytes using an adoptive transfer approach in athymic nude mice was investigated. The results indicated that Cy, at a dose (100 mg/kg) which virtually abolished anti-sheep erythrocyte (SRBC) antibody plaque forming cell (PFC) response of Balb/c mice, did not alter significantly the capacity of their splenic T cells to restore the anti-SRBC PFC response of nude mice. This resistance of T helper cells was observed in unimmunized mice and in mice injected with SRBC two days prior to Cy administration. It has been concluded that both resting and antigen stimulated T helper cells responsible for reconstituting anti-SRBC response of nude mice are resistant to Cy.

Animals↗
PubMed1982

Selective action of alkylating agents against cells participating in suppression of antibody responses.

The effect of several alkylating agents on the induction and expression of specific suppressor cell activity induced by supraoptimal immunization (SOI) with (4 x 10(9) ) SRBC was studied. Splenocytes taken 8-28 days after SOI and transferred to normal syngeneic recipients together with optimal dose of (3 x 10(8) ) SRBC caused 70-90% suppression. By contrast splenocytes harvested 2 days after SOI did not exert a significant suppressive effect. Treatment of donor mice with 30 mg/kg BCNU, CCNU, or MeCCNU, 8 mg/kg Melphalan or as much as 200 mg/kg Cy 2 days before SOI uniformly had no effect on the subsequent development of suppressor cells. By contrast, different drugs had diverse effects when injected after SOI: both BCNU and Cy injected 2 days post SOI alleviated suppression, whereas CCNU, MeCCNU and Melphalan injected 2 days post SOI were without effect. Another diversity between BCNU and Cy was noticed when the administration of drugs was delayed further. While Cy alleviated suppression 12 days post SOI, BCNU was ineffective at this time. Dose response and time course studies revealed that the effect of Cy was most severe when injected 2 days post SOI and gradually diminished with the passage of time after SOI. These results have been discussed in the light of the current concepts of multiple cell participation in the induction and expression of suppressor cell function.

Alkylating Agents↗
PubMed1981

Splenic alterations during mammary tumorigenesis: diverse effects on different immune parameters.

An evaluation of various parameters of the immune system was undertaken in Balb/c mice transplanted with a syngeneic mammary adenocarcinoma. Increasing tumor burdens resulted in a depression of some cell mediated immune functions. In contrast, an augmentation of humoral responses was observed in tumor-bearing mice. A defect in the immunoregulatory mechanism did not appear to be responsible for the elevated humoral response as revealed in suppressor cell experiments. However, flow cytometric analysis of T and B lymphocyte levels in the spleens of mice with mammary tumors indicated that the numbers of Thy 1.2 positive cells were greatly diminished while there was only a slight increase in the proportion of cells bearing surface immunoglobulin. These splenic alterations accompanying tumor growth might be responsible for the altered immune responses observed in tumor-bearing animals.

Adenocarcinoma↗
PubMed1980

Erythrocytes as carriers of chemotherapeutic agents for targeting the reticuloendothelial system.

The object of this work was to define a model using hypotonically loaded erythrocytes as a vehicle to target drugs to the reticuloendothelial system (RES). The optimum hemolytic event was found to occur at 100 mOsm/kg using a 0.5-min exposure at 0 degrees C. Approximately one third of the total volume of the cells could be replaced with hypotonic drug solutions under these conditions. Although cytosine-beta-D-arabinofuranoside, ara C, is membrane permeable and could not be entrapped in the erythrocytes, phosphorylation of this nucleoside antimetabolite enabled it to be loaded efficiently. Actinomycin D could be loaded and retained within the cells at 0 degrees C, but 90% of this loaded drug leaked out of the erythrocytes in 1 min at 37 degrees C. Actinomycin D-DNA complexes, however, could be loaded and retained for longer periods. In this case, 50% of the DNA-bound drug was retained in the cells for one hour at 37 degrees C. It was found that the glycopeptide antitumor antibiotic, bleomycin, could be entrapped and retained in the cells without appreciable leakage. It was possible to load a human therapeutic dose of this drug in 1-2 ml of packed cells. Furthermore, it was demonstrated that bleomycin entrapped in erythrocytes was significantly more effective than the same dose of free drug in suppressing the phagocytic function of the RES in Balb/C and C3H mice. The rationale is discussed for the possible use of these drugs, entrapped in erythrocytes, for the production of RES blockade in the treatment of disorders in man.

Antineoplastic Agents↗
PubMed1979

Suppressor activity of splenocytes from mice treated with Ecteinascidia turbinata extract.

Extracts of a marine tunicate, Ecteinascidia turbinata (Ete) were previously shown to be capable of suppressing humoral and cellular immune responses in vivo and in vitro. In the present work we have examined the mechanisms of suppression in Ete-treated DBA/2 and BALB/c mice. Treatment with Ete resulted in a significant splenomegaly accompanied by a diminished response to mitogenic stimulation, reaching coincident maxima of effect at days 4 to 6. Spleen size and blastogenic reaction returned to normal at 12 to 21 days. Cells from enlarged spleens inhibited blastogenic responses of normal splenocytes to Con A. Marker studies indicated that the suppressor activity was exerted by cells possessing T lymphocyte characteristics.

Animals↗
PubMed1978

Immunomodulation by Corynebacterium parvum. 1. Variable effects on anti-sheep erythrocyte antibody responses.

Corynebacterium parvum injected i.p. 1--16 days prior to i.p. antigen inoculation virtually abolished both IgM and IgG primary responses to 1 X 10(8) SRBC. The suppression was significantly marked at antigen doses ranging from 1 X 10(6)--1 X 10(9) SRBC but not at 5 X 10(9) SRBC. As little as 56 microgram C. parvum caused a marked suppression of the response to 1 X 10(8) SRBC. In secondary responses C. parvum given either one day before priming with 1 X 10(8) SRBC or one day before secondary challenge caused a dramatic suppression of both IgM and IgG PFC responses. In contrast with i.p. injected C. parvum, i.v. injection of the vaccine enhanced immune responses to i.p. or i.v. injected SRBC. Similarly C. parvum injected i.p. prior to i.v. immunization resulted in an augmented anti-SRBC response. An enhancement of anti-SRBC response was also noted when C. parvum was injected i.p. on the day of i.p. immunization. The suppressed responses in C. parvum injected animals could be explained partly by the reduced splenic localization of the antigen.

Animals↗