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D A Clark

Publications and source records attributed to D A Clark.

At least 289 records · Page 16Linked to original sources
PubMed1987

Local active suppression and successful vaccination against spontaneous abortion in CBA/J mice.

We report here that vaccination of CBA/J female mice with DBA/2 X BALB/c recombinant line that decreases the spontaneous abortion rate increases local active decidua-associated suppressor cell activity. In contrast, vaccination with a recombinant line that increases the abortion rate decreases suppressor cell activity. No correlation was seen between the effect on the abortion rate and the ability of cells from the fetoplacental unit to inhibit cytolysis by NK cells. Successful vaccination against spontaneous abortion may act primarily by augmenting suppressor cell activity in the decidua at the implantation site.

Abortion, Habitual↗
PubMed1987

Immunological and para-immunological mechanisms in spontaneous abortion: recent insights and future directions.

Unexplained spontaneous abortion in humans is currently thought to be related to genetic or immunologic factors. Animal models of spontaneous abortion have been used to try to gain some insight into the problems in humans. From studies of animal models there is increasing evidence that a variety of mechanisms may initiate pregnancy failure and participation of immunologic effectors may be a secondary event. Recent studies indicate that murine abortion that occurs spontaneously (without deliberate immunization by the investigator) may be initiated by para-immunologic host effector cells such as NK cells, macrophages and their toxins that possess selective toxicity which is not antigen-specific. The potential importance of local non-specific suppressive mechanisms in the uterus is also highlighted by their ability to block non-specific para-immune effector cell activation, and by their potential relationship to growth factors in decidual supernatants that promote placental cell growth in vitro. Levels of non-specific suppression do not appear low when fetal death can be attributed to a genetic mutation. The concept that different tissue components of the feto-placental unit serve as targets of different immunologic and para-immunologic effectors is defined. The new insights into the pathophysiology of murine abortion and its correction can provide a useful framework for further analysis of the role of para-immunologic effector mechanisms in unexplained abortion in humans and in non-murine veterinary conditions.

Abortion, Spontaneous↗
PubMed1987

Characterization of hormone-dependent suppressor cells in the uterus of mated and pseudopregnant mice.

The survival of the implanted "fetal allograft" has been attributed to the action of local decidua-associated suppressor cells. These suppressor cells are Fc-receptor positive small lymphocytic cells lacking T-cell markers which arise following implantation, are localized at the implantation site, and block the action of IL-2 that stimulates NK and T effector cells. Kinetic studies have demonstrated the occurrence of an earlier peak of suppressive activity occurring 2-3 days after mating prior to implantation. The cells associated with pre-implantation suppression differs significantly from post-implantation suppressor cells. Velocity sedimentation studies show that early suppression is associated with large cells sedimenting at a modal velocity of 6-7 mm/hr. Suppressive activity from cells of similar size is also present in the uterine lining of hormonally-treated, pseudopregnant mice. In addition, suppressor cells can be demonstrated in the non-pregnant uterus at the time of estrus. These observations suggest suppressor cell activity may be hormonally regulated. The suppressor cell(s) in pseudopregnant mice bears Lyt 2.1 and Thy 1.2 surface antigens and suppressor(s) present in the pregnant animals bears Lyt 2.1 and Lyt 1.1. Although the suppressor cell was large, it did not appear to be a macrophage because it was resistant to antibodies to Mac-1 and FcR cell surface markers but susceptible to anti-T cell reagents. Furthermore, suppression was not mediated by a soluble factor that has been associated with the small lymphocytic suppressor. Thus, the suppressor activity present in the pre-implantation uterine lining appears to differ significantly from the suppressor cell activity found after implantation. The possible role of a hormone-activated suppressor T cell in the success of the pregnancy is discussed.

Animals↗
PubMed1987

Surfactant displacement by meconium free fatty acids: an alternative explanation for atelectasis in meconium aspiration syndrome.

Meconium, an ether extract of meconium, and the major free fatty acids of meconium (palmitic, stearic, and oleic acids) were all found to increase the surface tension minimum of dog lung extract in a Wilhelmy balance. Each of these fractions was instilled into the lungs of dogs (15 experimental, eight saline solution controls), and cardiac output, venous and arterial blood gases, pulmonary, atrial, and systemic pressures, airway pressure, and static lung compliance were serially monitored for 2 hours. Mean airway pressure increased and static lung compliance decreased significantly in all of the experimental groups. Although arterial pH and PaCO2 and the various hemodynamic measurements did not change during the experiment, PaO2 decreased significantly and did not return to baseline in all experimental groups. Extracts from atelectatic portions of experimental dog lung had a surface tension minimum of greater than 20 dynes/cm, whereas airway foam had a surface tension minimum of less than 10 dynes/cm, suggesting that the free fatty acids of meconium are able to strip surfactant from the alveoli.

Animals↗
PubMed1987

Percutaneous transluminal angioplasty of stenotic coronary artery bypass grafts: 5 years' experience.

In a 60 month period (January 1981 to December 1985), 82 patients (79% male with a mean age of 60 years) had 83 saphenous vein grafts and 5 internal mammary artery grafts with a total of 101 stenotic sites treated with percutaneous transluminal coronary angioplasty. The mean time between bypass surgery and angioplasty was 51.2 months. The procedure was technically successful in 85% of patients, 86% of grafts and 85% of the sites attempted. In these cases, the mean diameter stenosis was reduced from 77 +/- 14 to 27 +/- 20% (p less than 0.001), the mean pressure gradient from 49 +/- 16 to 7 +/- 6 mm Hg (p less than 0.001). Emergency coronary artery bypass graft surgery was necessary in one patient (1.2%) whereas myocardial infarction occurred in three patients (3.6%). There were no hospital deaths. Clinical follow-up was obtained in all 82 patients. Before angioplasty, 23% were in Canadian Cardiovascular Society functional class II, 60% in class III and 17% in class IV. With a mean clinical follow-up period of 21.4 +/- 2.3 months, 71% are in class I, 17% in class II and 12% in class III. There were two deaths, 3 months or more after angioplasty, one probably due to graft closure. So far, angiographic follow-up (at 7.9 +/- 2.1 months) has been available in 26 patients. Ten patients (with 10 grafts) exhibited graft restenosis; six of them have had second successful repeat angioplasty. Among the many variables analyzed, statistically significant predictors of success were a higher measured balloon/graft ratio (p less than 0.001), smaller diameter graft (p less than 0.001), and shorter lesion length (p less than 0.01). The only predictor of complication was diffuseness of disease in the graft (p less than 0.05). The statistically significant predictors of recurrence were the residual stenosis after the initial angioplasty (p less than 0.01) and the measured balloon/graft ratio (p less than 0.01). Angioplasty of coronary artery grafts appears to be a feasible and efficacious procedure with a low complication rate. The technique is a satisfactory alternative to repeat surgery in selected patients.

Adult↗
PubMed1987

Acute pancreatitis: results of a protocol of management.

To assess prognostication and therapy of 100 patients with acute pancreatitis, a randomized prospective multicentre clinical trial was commenced in August 1982. This study examines the usefulness of four parameters (sex, age, serum amylase and serum aspartate aminotransferase), coincidentally used as part of accurate and reliable prediction of severity of disease, in predicting gallstone aetiology, with an accuracy of 82%. The cost effectiveness and morbidity associated with the treatment of pancreatitis is also examined; patients with mild to moderately severe pancreatitis are better managed with a peripheral intravenous crystalloid solution and routine ward observations, rather than with supplementary urinary catheter and antibiotics. Conclusions about the optimum treatment of patients with severe pancreatitis cannot be made; certainly peritoneal lavage as adjunctive therapy, which has not been shown to be beneficial in larger series of patients with severe pancreatitis, more than doubles the cost per patient and is thus probably not cost effective. The overall morality in this series is 2%.

Acute Disease↗
PubMed1987

Histopathologic alterations in the decidua in human spontaneous abortion: loss of cells with large cytoplasmic granules.

The histopathology of decidua obtained from the placental bed was evaluated by phloxine-tartrazine staining, which allows clear definition of cells with cytoplasmic granules. Mononuclear cells with large granules were seen in biopsy specimens taken from women at 8-31 weeks of normal pregnancy. In contrast, cells with large granules were missing in sections taken from the decidua of five women who were aborting or were destined to abort. Since the presence of suppressor cell activity in murine decidua correlates with the success of pregnancy and since this suppression is associated with small lymphocytes with cytoplasmic granules, the observations made using human placental bed biopsy material suggest that a possible suppressor cell deficiency might occur in the early stages of spontaneous abortion in human females.

Abortion, Spontaneous↗
PubMed1987

Antisperm antibodies detected by ZER enzyme-linked immunosorbent assay kit are not those detected by tray agglutination test.

Antisperm antibodies may play a role in the pathogenesis of infertility, particularly in the male. One of the standardized methods for detecting antisperm antibodies is the tray agglutination test (TAT). Unfortunately, this assay requires fresh motile spermatozoa. Tests for binding of antibody to fixed sperm or sperm extracts have been developed as enzyme-linked immunosorbent assays (ELISA), and we compared the results of using one such ELISA method with the TAT to detect antisperm antibodies in a panel of known positive and negative sera from infertile and control patients. With respect to the TAT assay, the ELISA gave a 75% false-positive test rate and a 63% false-negative rate. It is important to validate new assays such as the ELISA before widespread application to patient screening particularly since patients judged to have antisperm antibodies may be treated with high-dose corticosteroid drugs that are not without significant side effects.

Antibodies↗
PubMed1987

Induction of megakaryocytic colony-stimulating activity in mouse skin by inflammatory agents and tumor promoters.

The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with beta-methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by beta-methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

Animals↗
PubMed1987

Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer. A multicenter, randomized clinical trial by the National Cancer Institute of Canada.

The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%; p less than 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p less than 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.

Adult↗
PubMed1987

Health codes for newborn care.

A survey was conducted of the health departments in each of the 50 states, Washington, DC, and the Commonwealth of Puerto Rico to determine the present legal mandates for newborn care. Each of the 52 health departments were queried regarding birth certificates, identification procedures, prophylactic eye care, umbilical cord care, use of vitamin K, Apgar scoring, and metabolic screening. In each category, the departments were asked whether the procedures were mandatory or optional. Birth certificates are uniformly required within the health codes of all states. Although in-hospital identification of newborns is required in most states, four states specifically require arm banding, and only New York State requires footprinting. Eye prophylaxis with silver nitrate is required in 49 states, with erythromycin or tetracycline allowed as topical alternatives in 42 states. Clamping of the umbilical cord is addressed by eight states. Parenteral vitamin K administration is mandated by only five states. Apgar scoring is addressed by 25 states. Newborn metabolic screening is available in every health department, although significant variations exist in the tests available.

Apgar Score↗
PubMed1986

Characterization of the cellular basis for the inhibition of cytolytic effector cells by murine placenta.

Direct suppression of cytolytic effector cell function by cells of the placenta may represent one mechanism that protects the "fetal allograft" from rejection by maternal transplantation immunity. Collagenase disaggregated murine placental cells block target cell lysis by natural killer, lymphokine-activated killer, and (CTL)-type killer cells. This inhibition is reversible and noncompetitive, similar to a previously described inhibitor of CTL found in spleens of mice undergoing an acute graft vs host (GVH) response. Velocity sedimentation separation of placental cells shows that the inhibitory activity is primarily associated with cells that cosediment with nucleated fetal erythrocytes. When these erythrocytes were lysed, an increased number of non-erythrocytic cells could be separated and under this circumstance, inhibitory activity was seen in association with either small white cells or fetal erythrocytes and with large white cells. There may be several cell populations in murine placenta that can inhibit cytolytic effector cells. The possible relevance of direct placental inhibition of cytolytic effectors to protection of the "fetal allograft" is discussed.

Animals↗
PubMed1986

Active suppression of host-versus-graft reaction in pregnant mice. VIII. The uterine decidua-associated suppressor cell is distinct from decidual NK cells.

The fetus resulting from allogeneic mating expresses a variety of antigens that may serve as targets for rejection by the maternal immune system. Accumulation of non-T suppressor cells into the uterine decidua of allopregnant mice may serve to prevent such rejection. It has been previously shown that the suppressor activity in decidua during the second half of murine pregnancy is predominantly associated with a population of small lymphocytes with cytoplasmic granules that lack T-cell markers and inhibit the generation of cytotoxic lymphocytes (CTL) against paternal alloantigens both in vitro and in vivo. Since natural killer cells (NK) also possess cytoplasmic granules and may regulate the murine immune response, we examined the hypothesis that the decidua-associated non-T suppressor cell may represent a regulatory type of NK cell. Similar to NK cells, the decidua-associated suppressor cell expressed FcR for IgG. Unlike NK cells, the decidua-associated suppressor cell proved resistant to treatment with anti-asialo GM1 + C'. Sedimentation velocity examination demonstrated that decidua-associated NK activity was associated with cell population with a modal sedimentation of 4 mm/hr that was larger than the decidua-associated suppressor population. Potent suppressor cell activity was also recovered from the decidua of NK deficient allopregnant bg/bg mice. Therefore, decidua-associated NK cells and suppressor cells represent two distinct populations.

Animals↗
PubMed1986

Detection and characterization of cytotoxic T lymphocyte precursors in the murine intestinal intraepithelial leukocyte population.

Highly purified preparations of intraepithelial leukocytes (IEL) were obtained from the small intestinal mucosa. Leukocytes from the lamina propria (LPL) were isolated and phenotypically compared with IEL to verify that IEL were minimally contaminated by LPL. Because approximately 80% of IEL expressed the Lyt-2 antigen usually associated with cytotoxic/suppressor T lymphocytes, we wished to determine if precursors for cytotoxic T cells were present in this population. In order to generate cytotoxic cells, IEL and spleen cells from CBA/J mice (H-2k) were co-cultured with irradiated allogeneic spleen cells (H-2d or H-2b) in a one-way mixed leukocyte reaction (MLR). Four to six days later, the cultured cells were assayed against 51Cr-labeled H-2d or H-2b tumor or Con A-stimulated lymphoblast target cells, and the specificity of alloantigen-stimulated IEL and spleen cells was compared. The cytotoxic cells derived from both tissues displayed antigen-specific lysis of the allogeneic targets. Treatment of effector cells, generated from intraepithelial or splenic precursors, with monoclonal antibodies against Thy-1.2, Lyt-1.1, or Lyt-2.1 antigens plus complement, decreased cytotoxicity 85 to 100%, even though only 20 to 50% of the cells were lysed. The alloantigen specificity and surface antigen phenotype of the cultured IEL cells were identical to those of spleen cells and allowed us to conclude that IEL contained a cytotoxic T lymphocyte precursor (CTLp). Further characterization showed that, like spleen, the intraepithelial CTLp was Thy-1+ and Lyt-1+ and their sedimentation velocity was the same but differed from intraepithelial natural killer cells. Although 80% of IEL were Lyt-2+, the frequency of CTLp in the IEL population was estimated to be threefold to fivefold lower than in spleen, and the Lyt-2+ cells were shown not to be an enriched source of CTLp. Thus, the function of the majority of the IEL is still not known. However, there exists within this population CTLp, which may be capable of being stimulated with luminal antigens.

Animals↗