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Biomedical subjects

G A Hashim

Publications and source records attributed to G A Hashim.

At least 109 records · Page 6Linked to original sources
PubMed1980

Diagnosis, stage, and prognosis of lung carcinoma by preoperative assay of lung tumor antigen-sensitive T lymphocytes.

Levels of circulating T lymphocytes sensitized to human lung tumor--associated antigens (LTA) were determined by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. These levels were correlated with detection, pathological tumor stage, and postassay survival of patients with lung carcinoma. Peripheral blood lymphocytes (PBLs), from patients found to have lung cancer, were incubated with LTA and produced increased AgARFC compared to PBLs incubated without LTA. Significant levels of LTA-sensitive T cells were found in preoperative PBLs of 80% of patients with Stage I disease (8/10, p < 0.0005), 60% of those with Stage II disease (3/5, p < 0.025), and 46% of those with Stage III primary lung cancer (12/26, p < 0.01), compared with 11% of patients with either benign lung lesions (2/12) or lung metastases (0/6) of nonpulmonary malignant tumors (by chi square analysis). Postoperative survival correlated significantly with preoperative levels of LTA-sensitive T cells by AgARFC assay within Stage I lung cancer (r = 0.807, p < 0.0005). Stage I + II (r = 0.689, p < 0.001), and Stage III (r = 0.657, p < 0.001, not treated with chemotherapy). Preoperative PBL from patients with Stage I + II lung cancer were more frequently sensitized to LTA in the AgARFC assay than from patients with nonpulmonary carcinomas (0/22) or cigarette smokers (1/7) without pulmonary lesions (p < 0.0005). These findings demonstrate a high rate of detection of early, resectable lung carcinomas by preoperative AgARFC assay of PBL sensitized to LTA, and a significant correlation of LTA-sensitive T cell levels with tumor stage and patient survival. The AgARFC assay may be of prognostic as well as diagnostic value in the evaluation of patients with lung carcinoma.

Antigens, Neoplasm↗
PubMed1980

The kinetics of T lymphocyte subpopulations in guinea-pigs sensitized with allogeneic transplantation antigens.

The kinetics of specifically sensitized T lymphocytes in the circulation and lymphoid tissues of guinea-pigs immunized with allogeneic transplantation antigens or with synthetic peptide sequence known to induce delayed-type hypersensitivity were documented by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. The results show that immunologically functional cells sensitized to a particular antigen do not remain in the circulation when the antigenic source has been withdrawn. These cells become sequestered in lymphoid tissue and may be recalled into the circulation shortly after the de novo administration of sensitizing antigen. The detection of antigen-sensitive T cells in the circulation was indicative of the presence of and failure to detect these cells and their eventual appearance in lymphoid tissues was related to depletion of the antigenic source.

Animals↗
PubMed1980

The protective effect of methyl prednisolone on the machine-preserved kidney.

Fifty cadaveric transplants were reviewed to determine whether graft failure was related to the method of preservation. Twenty-eight transplants were preserved by a combination of cold storage and perfusion with cryoprecipitated plasma. Twenty-two transplants were preserved by continuous perfusion with Plasmanate. The perfusate of 14 plasma-perfused kidneys contained 1.0 g of methyl prednisolone, whereas the Plasmanate contained only 100 mg hydrocortisone. Fourteen plasma-perfused kidneys functioned immediately (Group I), and 14 showed delayed function. Seventeen of 22 Plasmanate kidneys (Group III) functioned immediately. Of the Group I kidneys, 13 of 14 functioned for three to eight months, and eight (57%) are still functioning after two years vs. only three of 14 (21%) in Group II. Eleven of the 14 long-term surviving grafts were pretreated with methyl prednisolone. Only nine of the Plasmanate kidneys (39%) lasted more than three months; five (22%) survived more than 12 months. None of the Plasmanate-perfused kidneys that failed to function immediately lasted three months. It is concluded that immediate restoration of renal function after transplantation is a favorable sign for long-term graft survival. The addition of methyl prednisolone to the perfusate may enhance the survival of kidney allografts.

Graft Survival↗
PubMed1979

Circulating breast tumour antigen-sensitive T lymphocytes in early breast cancer and high risk benign breast disease.

Levels of circulating T lymphocytes sensitized to breast tumour associated antigens (BTA) were correlated with pathological tumour stage or benign histopathology in preoperative studies of 180 patients by the antigen-stimulated active rosette-forming T cell (AgARFC) assay. Incubation of lymphocytes with allogeneic BTA extracts produced increased AgARFC compared with incubation without BTA. Significant levels of BTA-sensitive T cells were found in 78 per cent of breast cancer patients compared with 23 per cent of patients with benign disease (P less than 0.0005, by X2). Over 93 per cent of stage I cancer patients responded to BTA, compared with 69 per cent of stage II patients (P less than 0.025) and 59 per cent of stages III-IV patients (P less than 0.005). Twenty-nine per cent of 42 patients with fibrocystic disease were positive to BTA in contrast to 8 per cent of 25 patients with fibroadenomas. This was a 3.6-fold higher incidence of BTA-sensitive T cells associated with fibrocystic disease than with fibroadenomas, which was in agreement with the increased breast cancer risk rate associated with fibrocystic disease. These findings suggest that the AgARFC assay may detect early malignant change in fibrocystic disease. The AgARFC assay was found to reliably detect early invasive carcinoma.

Adenocarcinoma↗
PubMed1978

Molecular bases for the difference in the potency of myelin basic protein from different species in Lewis rats.

The results of this study define the chemical bases for the difference in the encephalitogenic potency reported for the bovine and guinea pig myelin basic proteins. Studies with synthetic peptides showed that the sequence of peptide S53, H-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-OH, which is native to the guinea pig basic protein, is the minimum amino acid sequence necessary for inducing EAE in Lewis rats. The results of this study further showed that specific sequence modifications rendered the native bovine sequence highly encephalitogenic.

Amino Acid Sequence↗
PubMed1978

Myelin basic protein-stimulated rosette-forming T cells in multiple sclerosis.

A subpopulation of T lymphocytes sensitized to human myelin basic protein in peripheral blood of patients with multiple sclerosis, central nervous system (CNS) tumors, and cerebrovascular accidents was demonstrated by the antigen-stimulated, rosette-forming T-cell assay. A significant increase in the percent of active rosette-forming T cells was detected after in vitro exposure of peripheral blood lymphocytes to human myelin basic protein but not to histones. In contrast, peripheral blood lymphocytes from healthy controls and from patients with benign and malignant breast diseases were unresponsive to stimulation by either antigen. These results demonstrate a functionally active T-lymphocyte subpopulation sensitized to myelin basic protein in patients with multiple sclerosis and in patients with certain other CNS diseases.

Adult↗
PubMed1978

Cell-mediated immunity to donor antigens in renal allograft recipients.

The antigen-stimulated active rosette-forming T-cell (AgARFC) assay was adapted for the preoperative study of 21 consecutive kidney transplants (17 cadaver donors and four living related donors; five retransplants). Recipient peripheral blood lymphocytes were incubated for 15 minutes with donor histocompatibility antigens preparaed by sonication of donor peripheral blood or splenic lymphocytes. Recipient presensitization to donor antigens was expressed as the difference between active rosette formation in the presence (%AgARFC) and in the absence (%ARFC) of donor antigens. This antigen-induced difference is rosette formation (%AgARFC - %ARFC) for all patients ranged from - 7.0% to 24.2%. Of those patients with pretransplant sensitization greater than 6.3% (group I: mean, 13.2 +/- 3.0; n = 7), 71% had severe acute rejection requiring dialysis within the first 2 weeks of transplantation. In contrast, none of the patients with pretransplant values below 6.3% (group II: mean, -0.8 +/- 1.0; n = 14) had rejection requiring dialysis within the first 2 weeks. Group I patients had 43% graft survival at 1 month and 14% survival at 2 months, whereas group II had 86% graft survival at 1 month and 71% at 2 months. The AgARFC assay provided a rapid means of measuring recipient T-cell presensitization to donor alloantigens, which was correlated with the accelerated rejection of renal allografts.

Antigen-Antibody Reactions↗
PubMed1977

Experimental allergic encephalomyelitis in Lewis rats: chemical synthesis of disease-inducing determinant.

Two amino acid sequences from the same regions of guinea pig and bovine myelin basic protein which induce experimental allergic encephalomyelitis in Lewis rats were synthesized. The sequences of these two regions may be defined by residues 69 to 84 of the bovine basic protein. The encephalitogenic sequence from guinea pig basic protein (peptide S49), H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gin-Arg-Pro-Gin-Asp-Glu-Asn-OH, is a much more potent encephalitogen than that of H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH (peptide S8) found in the bovine protein. The primary structures of the two determinants are similar; however, a Gly-His deletion from the guinea pig sequence is noted. Study of the encephalitogenicity of peptide S49, peptide S8, and the parent proteins suggests that the difference in the encephalitogenic potency of the parent proteins in Lewis rats is due to a natural modification in the primary structure of their respective encephalitogenic determinants.

Amino Acid Sequence↗
PubMed1977

A new assay for T-cell mediated immunity to transplantation antigens.

The kinetics of circulating antigen sensitive T-cells were studied in Hartley strain guinea pig recipients of Shorthair strain first- and second-set skin allografts. Peripheral blood donor antigen sensitive T-cells (AST) were quantitated by the antigen-stimulated active rosette-forming T-cell (AgARFC) assay by incubating lymphocytes in the presence and in the absence of soluble transplantation antigens. The number of circulating AST/cu mm rose to maximum levels (1,165 +/- 272 SEM) by day 3 and fell sharply before first-set graft rejection (453 +/- 117 SEM) on day 7 after transplant. In contrast, there were no detectable antigen-sensitive cells when lymphocytes from both recipient and control guinea pigs were stimulated with soluble recipient-strain antigen. Significant numbers (212 +/- 159 SEM) of circulating AST remained through day 68 after first-set grafts. Following placement of sencon-set allografts on day 73, the AST disappeared from the circulation for 2.5 days and then rose to peak levels (825 +/- 167 SEM) in circulating AST (579 +/- 327 SEM) preceded rejection of second-set skin allografts. When control guinea pigs were immunized with a single dose of soluble donor antigens, a progressive increase in circulating AST (579 +/- 327 SEM) was found through day 17 after sensitization without the fall associated with graft rejection. The antigen-stimulated, rosette-forming T-cell assay may prove useful in the detection of cellular presensitization and in the monitoring of graft rejection in clinical transplantation.

Animals↗
PubMed1976

Suppression and reversal of allergic encephalomyelitis in guinea pigs with a non-encephalitogenic analogue of the tryptophan region of the myelin basic protein.

The administration of synthetic peptide S42 leads to suppression and reversal of experimental allergic encephalomyelitis (EAE) induced in guinea pigs by myelin basic protein. Peptide S42 contains a linear sequence of 21 amino acid residues, H-Phe-Ser-Trp-Gln-Lys-Phe-Ser-Trp-Gln-Lys-Phe-Ser-Trp-Gln-Lys-Phe-Ser-Trp-Gln-Lys-Gly-OH, made up of four repeating unit sequences of H-Phe-Ser-Trp-Gln-Lys-OH in addition to a C-terminal glycine. Injected at relatively high doses, peptide S42 is non-encephalitogenic. It induces delayed-type hypersensitivity which is not followed by EAE, and elicits delayed-type hypersensitivity responses in peptide S42, encephalitogenic trytophan peptide, or BP-challenged animals for either of the three antigens. The repeating unit sequence of peptide S42 is analogous to the encephalitogenic tryptophan region of the BP molecules . The sequence homology is responsible for cellular recognition of this antigen by the skin test assay and suggests in vivo interaction between peptide S42 and EAE-inducing cells leading to suppression and reversal of disease.

Animals↗