PubMed Health⌕ Search

Biomedical subjects

D M Strong

Publications and source records attributed to D M Strong.

At least 55 records · Page 3Linked to original sources
PubMed1983

Seminal fluid excretion of cytomegalovirus related to immunosuppression in homosexual men.

Seminal fluid samples from 84 Danish homosexual men were successfully cultured to determine the prevalence of cytomegalovirus excretion. Ten (15%) out of 66 men positive for the antibody were found to be excreting the virus. Although the proportion excreting was inversely related to age (p less than 0.01), three men aged over 30 and with many years of homosexual experience excreted the virus. In addition, a 50 year old man with Kaposi's sarcoma excreted the virus. A further study of the ratio of T cell helpers to suppressors in the men aged over 30 and a series of age matched non-excreting homosexual control or heterosexual men showed that those excreting cytomegalovirus in their seminal fluid had statistically lower ratios (all less than 0.77) than the controls (p less than 0.05). Excretion of cytomegalovirus may be related to re-emergence of latent infection in immunosuppressed homosexual men.

Adolescent↗
PubMed1983

Genetic linkage and HLA association in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Twenty-eight families of patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency were studied to evaluate the specific HLA linkage relationship and HLA antigen association to the 21-OH deficiency gene. Genotype assignment, based on hormonal studies (ACTH stimulation) and HLA genotyping, correlated very well (p less than 0.01) in 23 unaffected sibs of children with 21-OH deficiency further supporting the genetic linkage of the 21-OH deficiency gene to the HLA complex. One family was informative for the placement of the 21-OH deficiency gene outside the HLA complex on the HLA-DR locus side. In this family HLA-A, B, C, DR, MT, MB, and glyoxylase typing and mixed lymphocyte culture was performed. An association of 21-OH deficiency and the HLA-A3 antigen was noted in the 28 families. This association is not secondary to the association of the 21-OH deficiency gene with HLA-BW47.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Cyclic AMP as a mediator of prostaglandin E-induced suppression of human natural killer cell activity.

The role of cyclic AMP in mediating the prostaglandin (PG) E2-induced suppression of natural killer (NK) cell function was studied. Highly purified preparations of human large granular lymphocytes (LGL; which have been shown to be closely associated with human NK activity) and T lymphocytes were obtained by using Percoll gradients. Basal cyclic AMP was similar in both cell populations. With LGL, PGE2 (but not PGF2 alpha) suppressed NK activity (75%) and enhanced cellular cycle AMP (600%). In contrast, in small, high density T lymphocytes, PGE2 caused very small increases in cyclic AMP (20%). Phosphodiesterase inhibitors (PDEI) such as isobutyl methylxanthine and theophylline also increased cyclic AMP and suppressed NK activity in LGL. The effect of PGE2 and PDEI, in combination on cellular cyclic AMP and NK activity, was greater than the effect of each agent alone. Finally, exogenous derivatives of cyclic AMP also suppressed NK activity. These results indicate that in LGL, increased cellular cyclic AMP mediates the action of PGE2 on the suppression of NK activity.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Cell surface antigen expression in newborn cord blood lymphocytes infected with HTLV.

Human T cell lymphocyte lines, established from lymphoid tissues from patients with adult T cell malignancies infected with the human T cell lymphoma virus (HTLV), were used in co-culture experiments to infect newborn cord blood lymphocytes (CBL). The infected and non-infected CBL cell lines were typed for HLA alloantigen determinants and tested for cell surface antigens using selected monoclonal antibodies. Infected cord blood lymphocytes showed inappropriate expression of alloantigenic determinants of the HLA-A and -B alleles. The monoclonal antibody 4D12, detecting an antigen common to the HLA-B5 cross-reactive group, was reactive with all infected cultures; this determinant appeared de novo in CBL cells lacking B5 cross-reactive group antigens in the uninfected state, and it increased in density in the infected cultures where the HLA-B5 cross-reactive alloantigens were present in uninfected CBL. HLA-DR was expressed in low levels or not detected on non-infected cultured cord blood lymphocytes and was present on all infected cells. OKT4 positive cells predominated in infected cultures, whereas OKT8 positive cells decreased in number or were absent. The TCGF receptor also increased both in density and in percent positive cells in all infected cell lines. The results suggest that HTLV may be tropic for a subset of T cells expressing mature T cell markers and that viral infections directly affect expression of cell surface antigens controlled by the human major histocompatibility complex (MHC).

Adult↗
PubMed1983

Familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his 5 offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in the other patients; the unaffected sibling developed lung adenocarcinoma. Cell surface analysis showed that 2 of these patients shared a common surface immunoglobulin profile with mu- and delta-type heavy chains and kappa-type light chains, whereas a 3d sibling with CLL had elevated mu- and kappa-chains. The patient with spontaneous disease remission had a perturbation in the percentage of cells bearing these same markers, consistent with a subclinical persistence of her lympho-proliferative process. Immunogenetic markers were associated with the occurrence of CLL, but these B-cell alloantigens were not linked to HLA. Two patients had abnormalities of chromosome 12 in B- but not T-cells: One had trisomy 12; the other had a mixture of dicentrics and translocations involving the same chromosome.

Aged↗
PubMed1983

Depression of natural killer cytotoxicity after in vivo administration of recombinant leukocyte interferon.

One hundred thirty-four patients with a variety of malignancies were treated in two phase I clinical trials of recombinant leukocyte A interferon (IFL-rA) produced by recombinant DNA methodology. IFL-rA was given by intra-muscular injection either twice daily or three times weekly for 28 days. Extensive monitoring of natural killer (NK) cell cytotoxicity was done on these patients with rigorously standardized assays and determination of the inherent variability of NK function for each individual. Interferon, as used in these two treatment regimens, failed to produce an appreciable increase in NK activity; in the majority of patients, there was no significant change in NK activity from the pretreatment baseline levels. An unexpected finding was the depression of NK activity in 30% of the patients. The data have been analyzed in terms of their possible relationship to dose and schedules of IFL-rA administration and to antitumor response.

Analysis of Variance↗
PubMed1982

Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes: variants M7 and DR1.

Comparative primary structural analyses have begun to elucidate polymorphic residues and segments of the class I antigens of the major histocompatibility complex, at least some of which presumably contribute to determinants important in immune recognition events. HLA-A2 structural variants have been described which are serologically indistinguishable from other HLA-A2 antigens, yet which can be recognized neither by HLA-A2 specific alloimmune nor by HLA-A2 restricted, virus immune cytotoxic T lymphocytes. This study utilizes double-label tryptic peptide comparisons in combination with both conventional and microsequence analyses to investigate the structure of two such variants, M7 and DR1. We find that these variants are identical with each other and differ from the predominant HLA-A2 heavy chain species by a glutamine to arginine substitution at residue 43, by an unidentified substitution in the tryptic peptide spanning residues 147-157, and by an as yet poorly defined alteration in glycosylation. Structural information from these and other variants should be useful in precisely defining functionally important determinants on the molecule.

Amino Acid Sequence↗
PubMed1982

Cryopreserved human cultured T cells as responder cells for the quantitative measurement of interleukin-2: improvement of the assay.

Large batches of human cultured T cells (CTC) were cryopreserved for later use as responder cells in a proliferation assay for measurement of interleukin (IL)-2 activity. Cryopreservation of CTC could be carried out without considerable loss in viability and cryopreserved and fresh cells showed equally good responses to IL-2. The conditions of IL-2-dependent CTC growth were analyzed, which led to a better evaluation of test results, and had important implications for the calculation of relative IL-2 activity. The repeated use of the same batch of cryopreserved CTC reduced test variability and provided an assay system that allows reliable and reproducible measurement of human IL-2 activity.

Cells, Cultured↗
PubMed1982

Amyl nitrite may alter T lymphocytes in homosexual men.

To evaluate the recent outbreak of Kaposi's sarcoma (KS) and opportunistic infections in homosexual men, clinical, virological, and immunological data on two homosexual men with KS and on fifteen healthy homosexual volunteers were collected. Both KS patients had regularly used amyl or butyl nitrite (AN); they had low helper/suppressor (H/S) T-lymphocyte ratios before chemotherapy and high titres of antibody against cytomegalovirus (CMV). Eight of the fifteen volunteers were regular AN users; seven of the eight had low H/S ratios due to larger than normal numbers of OKT8-positive suppressor cells and smaller numbers of OKT4-positive helper cells. In all eight AN users the fluorescence profile obtained with monoclonal antibody 9.6 (which detects the sheep E-rosette receptor) was bimodal, indicating a subpopulation of T cells with increased receptor density. A similar pattern was observed when OKT8, the antibody which detects cytotoxic suppressor cells, was used. Two of the seven men who did not use AN had abnormal fluorescence with reagent 9.6, and one of these also had a low H/S ratio. CMV-antibody titres were persistently high in fourteen of the fifteen healthy men, but the titres were not related to AN use of T-cell abnormalities. The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of DS and opportunistic infections in homosexual men.

Adult↗
PubMed1982

Morphologic observations of contact-induced lysis of EBV-infected B lymphocytes by autologous hand mirror T cells.

To study the possible immunologic role of hand mirror lymphocytes (HML) in the control of Epstein-Barr virus (EBV)-infected B lymphocytes in patients with infectious mononucleosis (IM), we studied the in vitro interactions of these cells by time-lapse video light microscopy. Peripheral blood T lymphocytes isolated from three patients in the early recovery phase of IM were mixed with their autologous EBV-infected B cells. Motile lymphocytes with their characteristic hand mirror shape were observed to attach by their uropods to the B cells. The HML remained attached for variable periods ranging from 45-75 min. Following detachment, B cells that were in contact with HML underwent lysis. Mixtures of T cells from healthy donors and EBV-infected cell lines exhibited only rare uropod formation with no attachment or lysis of B cells. The present experiment indicates that contact-induced lysis of EBV-infected B lymphocytes is operative in IM and that this process is mediated by the HML.

B-Lymphocytes↗
PubMed1982

Cryopreservation of human mononuclear cells for quality control in clinical immunology. I. Correlations in recovery of K- and NK-cell functions, surface markers, and morphology.

Cryopreserved human peripheral blood mononuclear cells (PBMC) were tested for natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) and for high-affinity (29 degrees C) and total (4 degrees C) rosette formation with sheep erythrocytes. PBMC produced variable NK activity following freezing and thawing, but consistently reacted well in ADCC. A significant correlation was found between low NK activity and a decreased percentage of low-affinity rosette-forming cells. On the contrary, the number of large granular lymphocytes (LGL), among which NK cells are restricted, and the reactivity with the monoclonal antibody OKT10, which recognizes the majority of LGL in the peripheral blood, were not significantly altered by cryopreservation. Cryopreserved cells proved to be excellent controls for determining the day-to-day variability of the NK assay and for selecting optimum conditions for this test in the clinical immunology laboratory.

Animals↗
PubMed1982

Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: possible implications for the generation of HLA polymorphism.

The primary structure of two highly crossreactive human histocompatibility antigens, HLA-A28 and HLA-A2, has been determined to 96% and 90%, respectively, of the papain-solubilized molecules. Their sequences have been compared with the sequence of HLA-B7 and with each other in order to outline the sites of diversity. The overall homology between HLA-B7 and these HLA-A antigens is 86%. A large majority of the differences are located between residues 43 and 195. Within this area, substitutions cluster in at least three segments--residues 65-80, 105-116, and 177-194. HLA-A28 and HLA-A2 show 96% homology. Most of the differences fall within segments 65-74 and 107-116. These results strongly support the suggestion that residues in these segments are integral parts of the alloantigenic determinants of HLA-A28 and HLA-A2. It is further proposed that these three clusters may constitute major, albeit not exclusive, sites of antigenic diversity in human histocompatibility antigens. The nature of the differences among HLA-B7, HLA-A28, and HLA-A2 in the first variable segment suggests that gene conversion might play some role in the generation of HLA polymorphism.

Amino Acid Sequence↗
PubMed1982

Donor-specific transfusion with diminished sensitization.

Fourteen mixed lymphocyte culture (MLC)-reactive haploidentical recipients have received donor specific transfusions (DSTs) with diminished sensitization to HLA antigens. A single unit of donor blood was obtained in CPD-A anticoagulant, packed, and transfused in three aliquots at 1-week intervals when the blood was 1, 3, and 5 weeks old. Transplantation, performed 22 to 149 days after the last DST, has been successful in all patients for 3 to 26 months except for one experiencing hyperacute rejection despite a negative crossmatch. In vitro studies suggest that blood storage results in the loss of T lymphocytes, which are presumably responsible for the sensitization, and preservation of B cells and monocytes, which remain capable of stimulating a cellular immune response in vitro throughout the 30-day storage period. Apparently this change in the cellular characteristics of blood with storage produces the salutory effects of blood transfusion without the undesirable sensitization to HLA antigens. The mechanisms remain under study.

Antilymphocyte Serum↗
PubMed1982

Evaluation of the immunogenicity of freeze-dried skin allografts in humans: cell-mediated response.

PATIENTS RECEIVING freeze-dried skin (FDS) allografts were evaluated for cell-mediated response by a lymphocytotoxicity test. Eleven patients received single or multiple FDS allografts from a donor typed for human leukocyte antigen (HLA). Heparinized blood samples were drawn before the procedure and at 2, 4, and 8 weeks after grafting. Mononuclear cells were isolated by Ficoll-Hypaque gradients. Cell-mediated lymphocytotoxicity tests were conducted, with mononuclear cells from the FDS allograft recipients used as effector cells. Phytohemagglutinin-stimulated blast target cells of the same HLA type as that of the skin donor were labeled with chromium 51. Lympholysis was evaluated by measuring the amount of 51Cr release after 18 hours' incubation with target/effector cell ratios of 1:100, 1:50, and 1:25. Negative control wells contained target cells alone. Positive control wells contained target cells and effector cells sensitized in vitro against the target cells. Viability of effector cells was tested by trypan-blud dye exclusion and response to phytohemagglutinin. None of the experimental blood samples showed 51Cr release significantly greater than shown by the negative controls. Our findings of no cell-mediated response and the findings of a previous study showing no production of anti-HLA antibody in response to FDS allografts indicate that allogeneic FDS is an immunologically safe material for use in periodontal surgical procedures.

Cytotoxicity, Immunologic↗
PubMed1982

Fresh versus stored blood in donor specific transfusion.

Haploidentical, MLC responsive recipients were randomized to receive either fresh (less than 48 hours old) or stored donor specific transfusions (DST). In the stored DST group, one donor unit obtained with CPD-Adenine anticoagulant was split into three aliquots and administered as packed cells after 1, 3, and 5 weeks of storage. While 3/6 fresh DST recipients became sensitized to their donors, 0/12 receiving stored DSTs developed positive donor crossmatches. Eleven patients (three fresh, eight stored) have been transplanted and have had similar posttransplant courses. None of the stored DST recipients has rejected his transplant. Four recipients of stored DSTs are awaiting transplantation. Leukocyte enumeration and FACS analysis of aliquots of stored blood shown that cells bearing HLA-ABC antigens disappear with time while B cells and monocytes persist. Taken in concert, the observations suggest that favorable recipient conditioning for transplantation can take place without sensitization to HLA antigens by simply storing the blood prior to transfusion.

Adolescent↗