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Biomedical subjects

D E Martin

Publications and source records attributed to D E Martin.

At least 73 records · Page 4Linked to original sources
PubMed1987

Induction of cytotoxicity in human peripheral blood mononuclear cells by monoclonal antibody OKT3.

It has been previously reported from this laboratory that incubation of PBMC with OKT3 generates potent cytotoxic lymphocytes that can be targeted by using antibody heteroconjugates consisting of anti-target cell antibody and OKT3. In the present study these conjugates were used to explore the kinetics of induction of cytotoxicity in PBMC and the subpopulations of lymphocytes involved. It was found that in addition to conjugate-dependent cytotoxicity, a considerable amount of conjugate-independent cytotoxicity was generated during OKT3 stimulation. Although the conjugate-dependent activity resided in the CD8+ population, the conjugate-independent cytotoxicity was found to be a function of CD4-/CD8- natural killer-like cells. Being largely CD3-, those cells were most likely activated by lymphokines produced by OKT3-stimulated CD3+ cells. They were capable of killing not only tumor cells but also autologous lymphocytes. The CD4+ cells of some donors were found to exhibit low but clearly demonstrable cytotoxicity. Induction of cytotoxicity was characterized as an early event in T cell activation, correlating with the kinetics of RNA synthesis. Cytotoxicity, interleukin 2 receptor expression, and DNA synthesis declined after 3 days of activation with OKT3, indicating the existence of as yet undefined regulatory mechanisms.

Antibodies, Monoclonal↗
PubMed1987

The effect of halothane/nitrous oxide/oxygen mask induction on arterial hemoglobin saturation in cyanotic heart disease.

The effect of a halothane/nitrous oxide/oxygen mask induction on arterial hemoglobin saturation (SaO2) was studied in 25 patients with cyanotic congenital heart disease. During this induction the SaO2 increased from 80% +/- 2 (mean +/- SEM) in awake patients breathing room air to 86% +/- 1 after induction of anesthesia, with an average increase of 6.8% +/- 2 (absolute) (N = 25; P < .005). Patients were retrospectively divided into two groups, A and B. Group A patients had pulmonic infundibular stenosis (PIS) (N = 13) with the potential for variable pulmonary outflow tract obstruction. These patients had awake SaO, values of 76% +/- 3 that increased significantly after induction to 86% +/- 1, with an average increase of 10% +/- 4 (absolute) (P < .01). Group B patients did not have PIS; they had an awake SaO2 of 83% +/- 2, which rose insignificantly after induction to 87% +/- 1, with an average increase of 4% +/- 2 (absolute) (P > .1). Thus, the significant increase in SaO2 during induction for the entire group was primarily due to the large response of patients with PIS. No correlation was found between SaO2 and systolic blood pressure for the entire study population as well as for groups A and B separately. The lack of correlation between systolic blood pressure and SaO2 may indicate that relaxation of pulmonic infundibular stenosis is an important mechanism explaining the observed increase in SaO2 during anesthetic induction in group A (PIS) patients. Six patients had clinically important decreases in SaO2 during the induction of anesthesia, and airway obstruction was usually the cause. Anesthetic induction with halothane/nitrous oxide/oxygen leads to an increase in SaO2 in patients with many forms of cyanotic heart disease, but especially those with the potential for variable pulmonary outflow tract obstruction.

Adult↗
PubMed1987

Anesthetic management for cardiac transplantation in North America--1986 survey.

Cardiac transplantation has become an established part of the therapy of end-stage heart disease. The number of cardiac transplants performed, as well as the number of centers performing them, has increased dramatically in the past 2 years. A paucity of literature on the anesthetic management of patients undergoing cardiac transplantation prompted this survey of 46 United States and Canadian institutions. The report summarizes the perioperative anesthetic management of a total of 1,273 transplant recipients in 34 institutions. Generally, similar anesthetic techniques and agents were used. One notable exception was the percentage of institutions using perioperative pulmonary artery catheter monitoring. As determined from this survey, right ventricular failure remains the leading cause of inability to terminate cardiopulmonary bypass in this patient population. Further, in surveyed institutions, cardiac transplantation expends more physician as well as hospital resources per patient than coronary artery bypass surgery.

Anesthesia, General↗
PubMed1987

The cytolytic protein of human lymphocytes related to the ninth component (C9) of human complement: isolation from anti-CD3-activated peripheral blood mononuclear cells.

A 70-kDa channel-forming protein has recently been isolated from human large granular lymphocytes maintained in interleukin-2-dependent culture. The protein was shown to be immunochemically related to the ninth component of complement (C9) and was therefore designated C9-related protein (C9RP). Using the procedure that was developed for the isolation of C9RP from large granular lymphocytes--i.e., affinity chromatography employing anti-human C9 linked to Sepharose, a cytolytic protein has now been isolated from OKT3-activated human peripheral blood mononuclear cells. Nineteen to 40 micrograms of active protein was obtained from 1 X 10(9) human peripheral blood mononuclear cells after the cells were cultured for 3 days with OKT3 (monoclonal antibody to cell surface antigen T3). During this period, a marked increment occurred in the amount of the cytotoxic protein contained per cell, indicating that OKT3 induced de novo synthesis of the protein. By NaDodSO4/PAGE the molecular mass was determined to be 70 kDa. By ELISA the isolated protein and C9RP of large granular lymphocytes reacted to the same extent with anti-C9RP. Using K-562 or M21 human melanoma cells as targets, the cytotoxic activity of the isolated protein, in the presence of 5 mM Ca2+, was comparable to that of C9RP. The same cytolytic protein was isolated from peripheral blood mononuclear cells that were depleted of CD16+ cells prior to OKT3 activation and that consisted primarily of CD4+ and CD8+ T lymphocytes. These results suggest that the cytolytic protein of OKT3-activated cytotoxic T lymphocytes is identical with C9RP of interleukin-2-stimulated large granular lymphocytes.

Antibodies, Monoclonal↗
PubMed1987

Induction of synthesis of the cytolytic C9 (ninth component of complement)-related protein in human peripheral mononuclear cells by monoclonal antibody OKT3 or interleukin 2: correlation with cytotoxicity and lymphocyte phenotype.

Synthesis of the cytolytic C9-related protein (C9RP) was induced by activation of resting human peripheral T lymphocytes with the anti-CD3 antibody OKT3 or interleukin 2. Comparison of cellular cytotoxicity and C9RP content at various times during activation yielded a coefficient of correlation r = 0.92. During OKT3 stimulation of peripheral mononuclear cells, maximal C9RP content and cytotoxicity were observed by day 2 or 3, with subsequent decline to baseline values by day 5, whereas during interleukin 2 stimulation, both parameters reached the maximal level at days 3-5. After fluorescence-activated cell sorting, C9RP and cytotoxicity were quantitated in CD4+, CD8+, and Leu-19+ subsets. In OKT3-activated CD8+ cells, C9RP increased to approximately 3 X 10(6) molecules per cell, with a corresponding increase in lysis of human melanoma cells mediated by anti-CD3-anti-melanoma monoclonal antibody conjugates. Interleukin 2-stimulated CD8+ cells showed similar increases, but cytotoxicity was conjugate-independent. Activated CD4+ cells showed minimal increase in C9RP content. Leu-19+ cells, which exhibit natural killer cell activity, had a high C9RP content (approximately 2.5 X 10(6) molecules per cell) before stimulation.

Antibodies, Monoclonal↗
PubMed1987

Killing of human melanoma cells by the membrane attack complex of human complement as a function of its molecular composition.

The efficiency of the membrane attack complex (MAC) in killing M21 melanoma cells was determined varying the molar ratio of cell-bound C9:C8. It was found that C5b-8 produced functional channels as evidenced by 86Rb release and propidium iodide uptake; cell killing occurred in the absence of C9 with greater than 5 X 10(5) C5b-8/cell; the maximal molar ratio of C9:C8 was 6.6:1; using nonlytic numbers of C5b-8 (4.7 X 10(5)/cell), greater than 90% killing ensued at a C9:C8 molar ratio of 2.8:1 at which approximately 9,000 poly C9/cell were formed, and 50% killing at a ratio of 1:1; (e) when the MAC was assembled on cells at 0 degree C, consisting of C5b-8(1)9(1), and unbound C9 was removed before incubation at 37 degrees C, killing was similar to that observed when poly C9 formation was allowed to occur. Thus, MAC lytic efficiency toward M21 cells may be enhanced by but does not depend on poly C9 formation.

Cell Line↗
PubMed1987

Molecular mechanisms of cytotoxicity: comparison of complement and killer lymphocytes.

The membrane attack complex of complement is an amphiphilic fusion product of 5 glycoproteins, C5, C6, C7, C8 and C9. The membrane attack complex forms transmembrane channels that vary in size depending on the number of C9 molecules incorporated into the complex. The C5b-8 complex forms small channels and at high multiplicity can kill nucleated cells. At least 12 C9 molecules are required to form tubular poly C9 which evokes the ultrastructural image of the classical membrane lesion produced by complement. The membranes of erythrocytes and other blood cells contain a 70,000 dalton protein that can inhibit channel formation by the membrane attack complex. This protein is species specific and has been called homologous restriction factor. A cytotoxic protein immunochemically related to C9 was isolated from cytotoxic human large granular lymphocytes and from OKT3 activated human peripheral blood mononuclear cells. In the presence of Ca++, isolated C9 related protein (C9RP) formed circular structures that resembled poly C9. C9RP efficiently killed K562 cells, human melanoma cells, Raji cells and human large granular lymphocytes. The results suggest that the channel forming protein of cytotoxic lymphocytes and C9 of complement have a common evolutionary ancestry.

Complement C9↗
PubMed1986

Electrostimulation of erection and ejaculation and collection of semen in spinal cord injured humans.

An electrostimulation system developed for early research with humans and the great apes, and a new constant-current stimulator specifically developed for human use, have been employed in studies with paraplegic men to produce erection and semen release by rectal probe electrostimulation (RPE). Catheter techniques for antegrade collection of the semen, uncontaminated by urine, have also been applied with moderate success. Details of the electronic instrumentation and catheter techniques are given. The procedure used with the patients and electrostimulation and semen collection results are presented.

Ejaculation↗
PubMed1985

Reproductive biology of paraplegics: results of semen collection, testicular biopsy and serum hormone evaluation.

The fertility and urological status of 30 male paraplegics between 20 and 47 years old with lesions between the T2 and L3 levels were examined by studying serum hormone levels (estradiol-17 beta, testosterone, prolactin, and follicle-stimulating and luteinizing hormones), sperm and semen characteristics via testicular biopsy and rectal probe electrostimulation, and urodynamic evaluation. Of the patients 13 had reflexic, 4 hyperreflexic and 13 areflexic bladders. Nine of the 13 patients with reflexic and all 4 with hyperreflexic bladders had a positive external sphincter electromyogram with detrusor-sphincter dyssynergia. When catheters were not used to collect semen during rectal probe electrostimulation, retrograde semen flow into the bladder was the rule. A total of 22 patients could tolerate rectal probe electrostimulation, while 6 who could not were injured at the T12 level or lower. Seminal emissions were obtained from 35 to 42 studies in these 22 patients. Total sperm count was variable; in 22 studies it was greater than 20 million. Progressive motility usually was low; 77 per cent of the patients had less than 20 per cent motility. Of 13 biopsy specimens obtained 6 suggested normal testicular morphology, with tubule atrophy and spermatogenic activity only mildly reduced in 6 of the remaining 7. Serum testosterone and luteinizing hormone values were significantly higher (p less than 0.05) among the paraplegic patients than among intact male volunteers of the same age range. Other serum hormone levels were unchanged. Outcome of rectal probe electrostimulation and biopsy did not relate to the number of years of patient injury. Thus, the principal deterrent to the use of semen collected by rectal probe electrostimulation from paraplegics for artificial insemination resides in a predominantly low sperm motility. Suggestions for improvement of motility include 1) great care to minimize or prevent urinary tract infections, 2) selection of medications for urinary tract care that do not compromise sperm survival and 3) prevention of sperm stagnation in lower tract storage sites, perhaps by use of periodical rectal probe electrostimulation.

Adult↗
PubMed1985

Current thinking in transplantation in infants and children.

Renal and liver transplantation are now recognized as therapeutic modalities for children with kidney and liver failure. This article reviews the general indications for transplantation, recipient selection, descriptions of the procedures, and the expected outcome of these two procedures in the pediatric setting.

Adolescent↗
PubMed1984

Effect of plasma fibronectin, macrophages, and glycosaminoglycans on tumor cell growth.

Fibronectin (Fn) synergizes with macrophages (M phi) in inducing cytostasis and cytotoxicity of neoplastic cells in culture. Since heparin enhances Fn's opsonic activity in many systems, we investigated its effect on Fn-macrophage synergy in cytostasis. MCG-T14 (a spontaneous mouse mammary adenocarcinoma) cells (4 X 10(4] were added to wells both with and without C. parvum activated M phi monolayers. To these cultures were added increasing concentrations of Fn with or without heparin. Fn synergizes with both M phi S and heparin in inhibiting tumor cell growth. The combined cytostatic effect of Fn, heparin and M phi S is more than additive. In other experiments, MCG-T14 cells were pre-incubated for 2 hr with Fn, washed free of Fn, and treated as above. The results of these experiments were similar to coculture experiments, but the effect of heparin was even more pronounced. Dermatan sulfate and hyaluronic acid had a variable effect on Fn and Fn-macrophage induced cytostasis.

Animals↗