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Biomedical subjects

J W Pearson

Publications and source records attributed to J W Pearson.

At least 37 records · Page 2Linked to original sources
PubMed1984

Cesarean section and perinatal mortality. A nine-year experience in a city/county hospital.

Presented is an analysis of experience from July, 1973, through June, 1982, in a teaching institution that served a high-risk urban population. The suggestion is made that improvement in perinatal mortality does not necessarily rely upon an ever-increasing cesarean section rate. During the 9 years encompassed by the study, the total cesarean section rate ranged from a low of 5.8% to a high of 8.2%. The primary cesarean section rate was first recorded separately in 1976, and stayed between 3.2% and 4.9%. During the same span of time, the uncorrected Perinatal Group II mortality rate dropped from 35/1,000 to 18/1,000. An attempt is made to interpret the various factors involved in accomplishing these results.

Birth Weight↗
PubMed1984

Busulfan versus cyclophosphamide treatment in the early and late stages of granulocytic leukemia in guinea pigs.

A transplantable granulocytic leukemia (GL-13-BC) in strain 13 guinea pigs, which has many similarities to human CML, was used to test the antineoplastic effects of two alkylating agents, busulfan and cyclophosphamide, administered in the late and early stages of the disease. Busulfan had a pronounced cytoreductive effect on circulating leukemic cells in the late, pre-blast crisis stage of this disease but all treated animals, succumbed to the leukemia with only a marginal increase in survival time relative to that of untreated controls. In this respect the guinea pig model resembles human CML. Survival time was moderately increased with early busulfan treatment but, as in the late treatment group, all animals succumbed to the leukemia. A pronounced cytoreductive action on leukemic cells was also observed in guinea pigs treated with cyclophosphamide. Late treatment with this drug produced highly variable effects on the survival time of leukemic guinea pigs; of the nine animals treated, no effect was observe in five, three showed a significant increase in survival time and one animal was still in remission without treatment when the experiment was concluded. Early treatment with cyclophosphamide produced the most striking finding of this study. Two treatments with this drug produced a complete remission in all of the treated guinea pigs. This remission lasted without further treatment for the duration of the study (greater than 200 days) while all untreated controls died within 27-37 days after receiving leukemic cell transplants. The relevance of these findings to the treatment of human CML is discussed.

Animals↗
PubMed1984

Selective antitumor effect on L10 hepatocarcinoma cells of a potent immunoconjugate composed of the A chain of abrin and a monoclonal antibody to a hepatoma-associated antigen.

The toxic A chain of abrin was isolated by affinity chromatography and was demonstrated to be a potent inhibitor of protein synthesis in a cell-free rabbit reticulocyte system with a complete inhibitory dose at 1 X 10(-9) M. This A chain was coupled by a disulfide linkage to a purified monoclonal antibody directed against a tumor-associated antigen found on the line 10 hepatocarcinoma tumor in strain two guinea pigs. The immunoconjugate retained the functions of the individual components, i.e., antigen binding to the intact cell in vitro and inhibition of its protein synthesis. This conjugate was a selective antineoplastic agent with a cytocidal dose at 5 X 10(-9) M toward antigen-bearing cells in vitro. Several antigen-negative cells were much less susceptible to its cytotoxic effect. The cytotoxicity of the conjugate appeared to be by antibody-mediated delivery of toxic A chain into the target cell. When cells were pretreated with excess free antibody followed by a brief exposure to conjugate, there was a reversal of the cytotoxicity to antigen-positive cells but not to the antigen-negative cells. The therapeutic efficacy of the conjugate was assayed by injecting a single dose s.c. or i.v. into syngeneic guinea pigs bearing established line 10 tumors. These in vivo studies showed that (a) the conjugate was not toxic at a dosage of 60 to 1120 micrograms/guinea pig, (b) the conjugate decreased or abolished the growth of established solid tumors, (c) the conjugate delayed or inhibited tumor metastases to lymph nodes, and (d) 20 to 40% of the animals in selective groups had a long-term complete regression.

Abrin↗
PubMed1984

Tumor models to investigate the therapeutic efficiency of immunomodulators.

The development of successful approaches to immunotherapy is dependent on the proper consideration of the pathobiology of metastasis and a better understanding of the principles of biological response modification. Immunomodulation as a therapeutic modality has not proven notably effective in animals with preexistent palpable disease, an observation in agreement with the results from clinical protocols. Therefore, rather than developing experimental immunotherapy models of immunoprophylaxis or models with minimal tumor burden, we believe it more appropriate to develop models based on preexistent metastatic disease in a tumor-conditioned host. The most rigorous test of a biological response modifier's efficiency prior to clinical trials will be provided from immunotherapeutic trials of palpable autochthonous tumors.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Treatment of canine transmissible venereal tumor by intravenous administration of protein A.

To determine if protein A can induce tumoricidal effects, transmissible venereal tumor-bearing dogs were treated by intravenous protein A administration. Each dog in the experimental group was treated twice a week with protein A, 100 micrograms/kg body weight, for a total of 10 treatments. Control dogs were treated with a 0.9% sodium chloride solution. No decrease in tumor volume attributable to protein A treatment was observed. However, transient healing of ulcerated tumors was observed in two dogs in the protein A-treated group but not in any in the control group. Following the first inoculation of protein A, a significant transient increase in polymorphonuclear cells and a significant transient decrease in lymphocyte and monocyte counts was detected, with a return of the counts to pretreatment levels by 24 h after the last protein A treatment. Intravenous protein A administration also failed to induce tumor regression in a guinea pig and a murine tumor model. These results suggest that the antitumor effects observed in protein A immunoadsorption studies have not been induced by leakage of protein A into the circulation.

Animals↗
PubMed1982

Neuropathy following paracervical block in the obstetric patient.

A distinct clinical syndrome of severe buttock pain radiating down the posterior surface of the ipsilateral leg and subsequent inability to ambulate has recently been recognized. The syndrome may develop in the parturient following a paracervical block. This study analyzes 4 cases from the authors' institution and reviews 2 cases from the literature. Onset of the syndrome ranges from 12 hours to 10 days but progressive improvement and complete recovery are the rule. The cause is believed to be secondary to direct trauma or hematoma formation in the area of the sacral plexus. Pelvic induration or a mass in the sacroiliac area may be noted bur abscess formation is not associated. Prevention is difficult but early recognition will facilitate treatment, which is mostly symptomatic.

Adolescent↗
PubMed1982

Inhibition of rat adenocarcinoma metastases by "Staphylococcus aureus" protein A.

Fischer F 344/CRBL female rats were injected intravenously with 10(6) syngeneic 13,762 adenocarcinoma cells, and daily doses of either 10 micrograms, 100 micrograms or 1 mg Staphylococcus aureus protein A were administered intraperitoneally on days 1 through 11. The animals were sacrificed on day 12, their lungs infused with Bouin's solution, and lung metastases counted. A significant reduction in the number of visible metastatic nodules was observed in the animals given 100 micrograms and 1 mg of Staphylococcus aureus protein A daily.

Adenocarcinoma↗
PubMed1980

Macrophage cytostasis and T and B cell blastogenic transformation in mice treated with nystatin.

Treatment of normal BALB/c mice with nystatin, an amphoteric polyene, activated macrophages to become tumoricidal for MBL-2 lymphoblastic leukemia target cells while augmenting the in vitro blastogenic response of splenic lymphocytes to B and T cell mitogens. These responses were both shown to be highly dose dependent and occurred 6 days following the intraperitoneal injection of nystatin into normal mice. Macrophages from untreated mice did not show similar activity. The significance of these observations and the potential use of nystatin as a pharmacologic agent is discussed.

Animals↗
PubMed1980

Fc receptor mediated immune regulation and gene expression.

Exogenous Fc receptors (FcR) have been demonstrated to either augment or inhibit endogenous FcR mediated immunity, immune regulation and gene expression. Other immune regulatory or modulator molecules, such as the H2 histocompatibility antigens, interferon, transfer factor and leukocyte chalones might involve association with or alter the synthesis or status of FcR, thus effecting regulation of immunity and/or gene expression. FcR provide a unique opportunity for eliciting the mechanisms and perhaps altering the immunity and/or gene expression which influence immune regulation, cellular differentiation, viral replication and malignant transformation.

Animals↗
PubMed1979

Positive rubella titers in pregnancy: a question of validity.

A review of 25 patients with more than 1 rubella titer by hemagglutination-inhibition testing revealed 3 patients with high positive titers that were reported to be negative in subsequent pregnancies. None of the patients had received the rubella vaccine. Because the sensitivity and reliability of hemagglutination-inhibition testing is markedly influenced by multiple variables, it is important for both the clinician and the pathologist to be aware of both the limitations of the testing method and the meaning of an antibody titer on a single isolated specimen.

Antibodies, Viral↗
PubMed1979

Neutralization of immune complex inhibition of antibody dependent cellular cytotoxicity in vitro by Staphylococcus-aureus protein A.

Staphylococcus-aureus protein A (SPA) incubated with sera containing immune complexes and effector cells increases antibody dependent cellular cytotoxicity (ADCC)and rosette formation. The enhanced ADCC and rosetting is due to SPA functioning as an IgG Fc cellular receptor. SPA binds to the Fc portion of Igg and has much greater affinity for immune complexes than free IgG. SPA bound immune complexes are blocked from attaching to the Fc cellular receptors via a competitive inhibition which neutralizes the inhibitory effect of these complexes on ADCC and rosette formation.

Animals↗
PubMed1979

Augmentation and inhibition of delayed hypersensitivity by Staphylococcus aureus protein A.

The injection of Staphylococcus-aureus protein A into mice, previously exposed to an antigen (sheep red blood cells), is capable of augmenting or inhibiting a primary delayed hypersensitivity (DH) response. SPA enhances DH response to SRBC when given with a greater than optimal sensitizing dose of the antigen. At antigen doses optimal for eliciting DH to SRBC, SPA inhibited DH. A proposed mechanism for the action of Staphylococcus-aureus protein A is based upon the ability of the protein to function as a Fc cellular receptor, thus neutralizing the effect of antigen-antibody immune complexes on DH. The binding of protein A to the Fc portion of antigen-antibody immune complexes effectively prevents subsequent binding of these complexes to Fc cellular receptors, thus eliminating their participation as co-factors in inter-cellular immunological communication. The ability of protein A to both augment and inhibit DH suggests a role for relative concentrations of serum factors and/or cellular receptors in the regulation of a primary DH response.

Animals↗
PubMed1979

Suppression of DNA synthesis in mitogen stimulated leukocytes with partial trypsin digests of Staphylococcus aureus protein A.

Staphylococcus aureus protein A (SPA) acts as a mitogen stimulating DNA synthesis and is not antagonistic to the mitogenic activity of other mitogens. The mitogenicity of SPA is due to the protein's multivalent Fc antibody receptors. Partial trypsin digestion of SPA yields monovalent Fc antibody receptors which are not mitogenic. Using a thymidine incorporation assay, results indicated that tryptic digests of SPA added to mouse splenic leukocytes 12 hours after stimulation with either concanavalin A, lipopolysaccaride or SPA suppressed the DNA synthesis normally elicited by these mitogens. SPA was digested with 1% trypsin at pH 8 for varying periods of time. As the digestion time increased from 0 to 60 minutes the mitogenicity of the SPA-trypsin digests decreased indicating cleavage from multivalent to monovalent SPA Fc antibody receptors. The decrease in mitogenicity of the SPA digests was directly associated with increased ability to inhibit DNA synthesis in mitogen stimulated leukocytes. A proposed mechanism for the inhibition of DNA synthesis suggests that SPA-monovalent Fc antibody receptors mimic cellular Fc receptor function thereby influencing cellular gene expression.

Animals↗
PubMed1975

Histological and combined chemoimmunostimulation therapy studies against a murine leukemia.

A Graffi murine leukemia was utilized as a model system to investigate the effect of chemoimmunostimulation therapy. Subcutaneous inoculation of approximately 1.0 times 10(6) tumor cells resulted in a rapidly growing tumor at the site of inoculation and subsequent development of splenomegaly and lymphoadenopathy. All animals succumbed to the leukemia within 24 to 30 days. Treatment of diseased animals with two courses of cytoxan over a 2-week period resulted in a remission period of approximately 16 to 18 days before relapse and eventual death of approximately 70% of the drug-treated animals. A significant number of long-term survivors (50 to 83%) was obtained in groups of animals that received combined drug plus BCG or C. parvum therapy. In contrast, the administration of MER (a methanol-extracted residue of BCG) to animals in a drug-induced remission period was no more effective than drug alone. The protective effect afforded by BCG and C. parvum was dependent on the time interval between drug therapy and the administration of the immunostimulators. Treatment of leukemic animals with BCG, C. parvum, or MER alone proved ineffective as all mice died at approximately the same time as untreated control animals. No leukemic cells were observed in any of the histologically examined tissues taken from long-term survivors. The implication of these results for cancer therapy is discussed.

Animals↗