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Biomedical subjects

D J Wilson

Publications and source records attributed to D J Wilson.

At least 235 records · Page 13Linked to original sources
PubMed1985

T-2 toxin can cause vasoconstriction in an in vitro bovine ear perfusion system.

An in vitro bovine ear perfusion system was used to examine the effect of T-2 toxin on peripheral vasculature. T-2 toxin caused a dose-related increase in the perfusion pressure, with an apparent threshold concentration of 1 X 10(-5) M. The effect of the toxin was observed irrespective of the presence of either histamine or norepinephrine in the system. The presence of known histaminic or noradrenergic antagonists did not affect the response to the toxin. Once the vessel was exposed to T-2 toxin, the response to histamine or norepinephrine was decreased.

Animals↗
PubMed1985

The human lymphokine-activated killer cell system. V. Purified recombinant interleukin 2 activates cytotoxic lymphocytes which lyse both natural killer-resistant autologous and allogeneic tumors and trinitrophenyl-modified autologous peripheral blood lymphocytes.

Culture of human peripheral blood lymphocytes (PBL) in purified natural or recombinant interleukin 2 in the absence of exogenous antigen or mitogen causes the differentiation of nonlytic precursor cells into lymphokine-activated killers (LAK). A titration of purified Jurkat IL-2 (BRMP, FCRC, NIH) IL-2 showed that the relatively low concentration of 5 U/ml was optimal for LAK activation. When the responding PBL were pretreated with either mitomycin C or gamma irradiation, LAK activation did not occur, indicating that proliferation, in addition to differentiation, is required. The spectrum of target cells susceptible to LAK lysis in a 4-hr chromium-51-release assay includes fresh NK-resistant tumor cells and trinitrophenyl (TNP)-modified autologous PBL. Unmodified PBL are not lysed. Cold target inhibition studies indicated that LAK lysis of autologous TNP-PBL is totally inhibited by fresh tumors cells, and that tumor lysis is inhibited by TNP-PBL. Additionally, allogeneic tumors totally inhibit lysis of autologous tumor cells in other cold target studies. These results demonstrate that the lytic activity expressed by LAK is not HLA restricted, is not limited to tumor cells, and is "polyspecific" as indicated by the cross-reactive recognition of multiple target cell types in these cold target inhibition studies.

Humans↗
PubMed1985

The differential inhibitory effects exerted by cyclosporine and hydrocortisone on the activation of human cytotoxic lymphocytes by recombinant interleukin-2 versus allospecific CTL.

Two immunosuppressive drugs, cyclosporine (CsA) and Hydrocortisone (Hy) were examined in parallel for their effect on the generation of cytolytic T lymphocytes (CTL). Peripheral blood lymphocytes (PBL) were stimulated with allogeneic cells to produce allospecific CTL, or with purified recombinant Interleukin 2 to activate lymphokine activated killer cells (LAK). CTL and LAK activity were measured in a 4 hr chromium release assay after 7 days of activation. Lysis by CTL was tested against stimulator PBL (not blasts) and LAK against fresh sarcoma tumor cells. At pharmacologic doses, CsA inhibited only CTL generation, and Hy inhibited only LAK. This greater understanding of the selective role, or roles, in vitro of CsA and Hy provides a basis by which to consider selective immune suppression--and, alternatively, the possibility of combining modalities for a more thorough immune suppression.

Cells, Cultured↗
PubMed1985

Detection and serotyping of herpes simplex virus in MRC-5 cells by use of centrifugation and monoclonal antibodies 16 h postinoculation.

Monoclonal antibodies (Syva Co., Palo Alto, Calif.) were used for the detection and serotyping of herpes simplex virus (HSV) isolates by immunofluorescence 16 h after inoculation of MRC-5 monolayers in 3.7-ml shell vials and after low-speed centrifugation. A total of 119 specimens were inoculated into conventional tube cell cultures and shell vials. Of 98 specimens inoculated on the same day of receipt in the laboratory (fresh specimens), all 23 (23.5%) HSV-positive specimens were identified by serotype in 16 h in shell vials by immunofluorescence, whereas only 8 of 23 HSV-positive specimens (34.8%) produced cytopathic effects in conventional tube cell cultures in this time period. Similarly, of 21 original specimen extracts previously determined to be culture positive for HSV (stored specimens), all were detected and serotyped by the immunofluorescence test with monoclonal antibodies 16 h postinoculation compared with the recognition of only 8 of these isolates (38.1%) by cytopathic effect that soon. This technique of centrifugal inoculation of HSV in shell vials containing MRC-5 cells permitted detection of this virus in all positive specimens with serotype determination within 16 h postinoculation.

Antibodies, Monoclonal↗
PubMed1985

Lymphokine-activated killer (LAK) cell phenomenon. IV. Lysis by LAK cell clones of fresh human tumor cells from autologous and multiple allogeneic tumors.

Activated killer cells are generated by the incubation of peripheral blood mononuclear leukocytes (PBL) in the lymphokine interleukin 2 (IL-2). Unseparated populations of these lymphokine-activated killer (LAK) cells lyse a variety of fresh noncultured human tumor targets, but they do not kill normal PBL. This study analyzed the generation and lytic specificity of LAK cell clones. Of 49 (84%) clones isolated by limiting-dilution techniques from a whole population of LAK cells, 41 manifested significant LAK cell activity. LAK cell clones had varied cell surface phenotypes. Clones with high and intermediate LAK cell activity were Leu 2+3-4+7-DR+Tac+ and Leu 2-3+4+7-DR+Tac+, respectively. Single LAK cell clones lysed multiple fresh human tumor targets including autologous sarcoma, 5 allogeneic sarcomas, and a colon cancer in addition to the cultured cell line K562. Autologous PBL were not lysed. Tumor targets were each lysed by multiple LAK cell clones. Sixteen subclones were derived from 5 of these LAK cell clones. These subclones had 99% or greater probability of being derived from a single cell. These subclones also exhibited lysis of multiple tumor targets. These findings suggest the existence of a shared determinant, expressed by multiple human tumors, which is recognized in common by multiple LAK cell clones.

Antibodies, Monoclonal↗
PubMed1985

Experimental analysis of the role of the ZPA in the development of the wing buds of wingless (ws) mutant embryos.

Phenotypically wingless (ws) chick embryos have wing buds characterized by the spreading of mesenchymal cell death in an anterior-to-posterior direction beginning at stage 19. It has been argued that this may reflect the absence of a functional polarizing zone (ZPA). When tested by preaxial grafting into normal wing buds (stages 20-21), wingless ZPAs (stage 18-19) had duplicating properties identical with those of normal ZPAs. Equally, normal chick or quail ZPA (stages 20-22) grafted into the posterior margin of wingless wing buds (stages 18-20) failed to inhibit the pattern of cell death or to evoke any improvement in their developmental performance. The wingless (ws) condition is not, therefore, due to a ZPA deficiency. Possible explanations are the prior programming for cell death of the wingless mesenchyme, or somitic deficiency, but it appears more likely that the mutant limb mesenchyme fails to transmit or respond to factor(s) produced by the ZPA.

Animals↗
PubMed1984

Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells.

In previous in vitro studies, the authors showed that phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL) from cancer patients to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. Thus, after IRB approval, a phase I clinical protocol was instituted in cancer patients who had failed all other therapy to determine the toxicity and effects, in vivo, of the infusion of large numbers of such PHA activated autologous PBL. Ten patients were treated on the protocol, six with sarcoma, one with melanoma, and three with colorectal cancer. Up to a total of 1.7 X 10(11) PBL were obtained from 7 to 15 successive leukaphereses, the cells from each leukapheresis being incubated in vitro in medium containing PHA and human AB serum for 2 days and then reinfused following the next leukapheresis 2 days later. Toxicity encountered included fever and chills in 10/10 patients, headaches in 5/10, nausea and vomiting in 3/10, and requirement for erythrocyte transfusion in 8/10. No evidence for autoimmune disease, abnormal serum chemical or coagulation studies, or pulmonary emboli was found. 111Indium trafficing studies showed distribution of infused cells mainly to the spleen and liver, with some accumulation in the lungs and tumor especially after repeated infusions. In 9/10 patients, activated PBL were detected in the peripheral circulation by the sixth leukapheresis. Evidence for this was found by assaying the incorporation of tritiated thymidine (3H-Tdr) into, and lysis of fresh tumor cells by, unstimulated PBL from successive leukaphereses. No tumor regression was seen in these patients with bulk disease. These studies demonstrated that large numbers of PHA-activated PBL can be safely obtained and infused into humans, achieving an increase in the number of circulating activated cells with evidence of migration of cells to tumor, lungs, liver and spleen. Further studies of the use of activated lymphocyte infusion in conjunction with chemotherapy in humans are in progress.

Adult↗
PubMed1984

The human mixed lymphocyte-tumor cell interaction test. I. Positive autologous lymphocyte proliferative responses can be stimulated by tumor cells as well as by cells from normal tissues.

Co-culture of cancer patients' nonadherent peripheral blood lymphocytes with irradiated autologous fresh tumor cells, termed the mixed lymphocyte-tumor interaction (MLTI) test, resulted in significant stimulation of 3H-Tdr in corporation on day 6 in 19 of 37 autologous combinations. The MLTI test was performed in a microtiter wells (0.2 ml) and a variety of solid tumor cells (sarcomas and carcinomas) were used. Tumor cells were dissociated from the fresh biopsy tissue by nontrypsin enzymatic digestion (deoxyribonuclease, hyaluronidase, and collagenase) and the tumor cells enriched by depletion of macrophages using adherence procedures. Occasionally, further tumor cell purification was achieved by separation of cells on the basis of size on dis-continuous gradients. Positive MLTI resulted in stimulation as high as 20-fold over the backgrounds of PBL and tumor cells cultured alone. Mean positive MLTI was SI of 7.7. The negative MLTI were not a reflection of generalized immunosuppression, because tumor cell preparations that did not stimulate autologous PBL did stimulate allogeneic PBL. In an additional patient, PBL not responding in the autologous MLTI did respond to allogeneic tumors. MLTI using cryopreserved cells reproduced the MLTI results using fresh cells in 11 of 16 tests; the other five tests were all positive in the fresh MLTI and negative when using cryopreserved cells. Despite reports from many other groups it appears that positive MLTI were not tumor-specific. In 14 experiments we were able to simultaneously test the proliferative response to autologous tumor as well as to an autologous normal tissue (lung, liver, colon, and bowel). In eight of these experiments positive responses were obtained with tumor stimulators and in seven of these, positive proliferation was also obtained with normal tissue.

Adenocarcinoma↗
PubMed1984

Intravenous labetalol in the management of severe hypertension and hypertensive emergencies.

The intravenous administration of labetalol, a combined alpha- and beta-adrenergic receptor blocking agent, reduced diastolic blood pressure by 30 mm Hg or more in 15 of 17 patients with severe hypertension (supine diastolic blood pressure greater than or equal to 125 mm Hg). A method repeated intravenous injection of the drug produced a prompt but gradual reduction of arterial blood pressure without the induction of a reflex tachycardia. Side effects were mild and of brief duration despite the presence of hypertensive complications in many of these patients. Hypotension, coronary insufficiency, or neurologic deterioration did not occur. Labetalol appears to be a suitable alternative to the direct vasodilating agents in the management of patients with severe hypertension and hypertensive emergencies.

Adolescent↗
PubMed1984

Comparison of iodine- and fluorescein-labeled monoclonal antibodies for detection of Chlamydia trachomatis inclusions in cells grown in glass vials.

A fluorescein-labeled monoclonal antibody was compared with the iodine stain for the detection of chlamydial inclusions in McCoy cells grown on cover slips in glass vials. The remainder of the original specimen extracts in 2-sucrose phosphate transport medium from 100 specimens (50 male, urethra; 50 female, cervix), stored at -70 degrees C and previously determined to be culture positive for Chlamydia trachomatis by the iodine stain, were inoculated into vials containing monolayers of McCoy cells. Cover slips were coded and examined microscopically after 40 hr at 35 degrees C. The mean numbers of inclusions detected by iodine and by immunofluorescence were the same. One-half of the specimens had eight or fewer inclusions present. There was a trend indicating that less time was required for microscopic examination of cover slips for chlamydial inclusions with immunofluorescence than with the iodine-staining method. The tagged monoclonal antibody is a high-quality immunodiagnostic reagent for use in the immunofluorescence test; however, our data derived from stored specimen extracts indicate equivalence of detection of inclusions in the glass vial system compared to iodine.

Antibodies, Monoclonal↗
PubMed1984

Arthrosonography of the painful hip.

Examination of the hip using ultrasound is described with anatomical correlation. Thirty patients with painful hips were examined; an effusion was detected in 16. Aspiration of the hip joint in 15 patients confirmed the ultrasound findings; there were no false positives or false negatives. In at least 12 patients the management was significantly influenced by the results of ultrasound examination.

Adolescent↗
PubMed1984

Functional test for the hemiparetic upper extremity.

A test, called the Functional Test, that evaluates the integrated function of the total upper extremity of an adult hemiparetic patient has been developed. It was used with 82 patients admitted to Rancho Los Amigos Hospital for stroke rehabilitation, together with a battery of six objective test measures. Sequential testing by two examiners demonstrated that the test had interrater reliability. The Functional Test score accounted for 87 percent of the variation in the scores achieved by the patients on the six separate objective measures. This tool integrates the information from these objective assessments and appears to be a valid measure of functional use of the hemiparetic upper extremity. The test can be administered in approximately 30 minutes, can be used in different treatment settings, and provides an accurate and immediate assessment of upper extremity capabilities.

Adult↗
PubMed1983

5-bromodeoxyuridine-induced amplification of prolactin gene in GH cells is an extrachromosomal event.

Treatment of a 5-bromodeoxyuridine-resistant (brdUrdr) and prolactin-nonproducing (Prl-) subclone of GH cells with this drug led to amplification of the prolactin (Prl) gene and induced Prl synthesis. Withdrawal of the drug treatment reversed both of these processes. In normal rats, the increased Prl synthesis observed during late pregnancy and lactation does not seem to be mediated via amplification of the gene. Amplification of the Prl gene and induction of Prl synthesis can also be observed in the Prl-, brdUrd-sensitive (brdUrds) GH cell strain. Prl gene amplification thus does not seem to be associated with the mechanism that confers the brdUrdr phenotype to these cells. brdUrd-induced amplification of the Prl gene can be identified with the low molecular weight, extrachromosomal, supernatant DNA fraction, isolated by Hirt's method. Southern blot analysis of Hirt's supernatant DNA (undigested) from brdUrd-treated cells generated a distinct band following hybridization with [32P]pDNAPrl-insert. The size of this band is greater than 23 kb but smaller than chromosomal DNA. Growth hormone (Gh) and albumin (Alb) gene sequences can be detected in the chromosomal DNA preparation but are absent in the extrachromosomal DNA prepared from Hirt's supernatant. The levels of Gh and Alb sequences are unaffected by brdUrd treatment of these cells. Results presented here suggest that in rat pituitary glands as well as in GH cells, hormonally controlled increased Prl synthesis is not caused by gene amplification. However, the brdUrd-induced expression of the Prl gene seems to be linked to the mechanism of drug-induced amplification of the Prl gene, mediated via an extrachromosomal event.

Animals↗