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Biomedical subjects

M Collins

Publications and source records attributed to M Collins.

At least 307 records · Page 17Linked to original sources

Adult age differences in memory elaboration.

Two experiments tested the hypothesis that elderly adults conduct less elaboration of information to be learned than young adults. In Experiment 1, young and elderly adults were tested for free and context-cued recall of target words embedded in sentences ending in relevant (precise) or irrelevant (imprecise) elaborations. In Experiment 2, young and elderly adults were tested for recall of words in sentences for which relevant or irrelevant elaborations were provided or sentences for which relevant or irrelevant elaborations were generated by the participants. They were also tested for memory of the elaborations themselves. Elderly adults showed as much benefit from the provision of relevant elaborations as young adults but were less likely to generate relevant elaborations. The results reflect age-related differences in elaborating stimulus words in terms of previous knowledge and in encoding specific attributes of sentence contexts.

Adolescent↗

Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose.

In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.

Adjuvants, Immunologic↗

Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose.

The systemic administration of multiple, nontoxic doses of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose [poly(I,C)-LC] eradicated established experimental and spontaneous pulmonary metastases. Optimal immunotherapy was schedule dependent, requiring three to five injections of poly(I,C)-LC per week for a minimum of 4 weeks; in addition, therapeutic efficiency was partially dosage independent. Immunotherapy by poly(I,C)-LC was found to be limited by tumor burden, although when combined with chemotherapy as a debulking regimen it resulted in increased survival with protocols in which poly(I,C)-LC alone was insufficient. These data suggest that the systemic administration of poly(I,C)-LC may provide a successful adjuvant therapeutic modality against cancer metastasis.

Adjuvants, Immunologic↗

Augmentation of NK cell activity in tissue specific sites by liposomes incorporating MTP-PE.

Liposomes incorporating a variety of immunomodulators have been shown to activate macrophages and monocytes for tumoricidal activity both in vivo and in vitro. We report that in addition to the activation of macrophages, the i.v. injection of liposomes (multilamellar vesicles) that have encapsulated muramyl tripeptide-phosphatidylethanolamine (MTP-PE) could also augment interstitial natural killer (NK) cell activity in the lung and the liver. In contrast, liposomes incorporating MTP-PE were unable to augment NK cell activity in the spleen, peripheral blood, or peritoneal cavity (after i.p. injection). In addition, liposomes did not augment splenic NK cell activity in vitro. This suggests that the augmentation of NK cell activity in the lungs and liver was not due to direct effects of the liposomes but may have been a secondary effect mediated by a monokine. The augmentation of pulmonary NK cell activity was paralleled by the nonspecific immunoprophylaxis of experimental pulmonary metastases. The augmented NK cell activity, as well as the enhanced nonspecific immunoprophylactic activity, was reduced by pretreatment of the mice with anti-asialo GM1 antiserum. Thus, the augmentation of organ-associated NK cell activity by liposomes incorporating MTP/PE plays a major role in the host's increased resistance to the formation of experimental metastases.

Acetylmuramyl-Alanyl-Isoglutamine↗

In vitro and in vivo analysis of the control of dihydrofolate reductase gene transcription in serum-stimulated mouse fibroblasts.

We have studied the rate of transcription of the gene for dihydrofolate reductase (DHFR) in mouse 3T6 fibroblasts during serum-induced transitions between the resting (G0) and growing states. As a model system, we have used a methotrexate-resistant 3T6 cell line that overproduces DHFR and its mRNA about 300-fold, yet regulates the expression of the DHFR gene in the same manner as normal 3T6 cells. In previous studies, we showed that the rate of production of cytoplasmic DHFR mRNA relative to total mRNA is about 4 times lower in resting than in exponentially growing cells. The rate increases to the growing value by about 15 hr following serum stimulation of the resting cells. This increase appeared to be controlled by regulating the rate of synthesis of DHFR hnRNA. In this study, we analyze the transcription of the DHFR gene in more detail. We use a variety of labeling times and RNA extraction procedures to measure the rate of synthesis of DHFR hnRNA relative to total hnRNA in pulse-labeled cells or in nuclei isolated from cells at various times following serum stimulation. The amount of labeled DHFR RNA is determined by DNA-excess filter hybridization. In all cases, the relative rate of synthesis of DHFR hnRNA increases at the same time, and to the same extent, as the rate of production of DHFR mRNA, suggesting that the increase in DHFR mRNA production is due to a corresponding increase in the rate of transcription of the DHFR gene. The increase in DHFR gene transcription is not blocked by cytosine arabinoside, showing that the increase does not depend on gene duplication. In isolated nuclei, DHFR RNA synthesis is inhibited by alpha-amanitin (1 microgram/ml), indicating that the DHFR gene is transcribed by RNA polymerase II. Others have shown that when stationary phase cells are stimulated to proliferate, the increase in DHFR mRNA content is controlled primarily at the post-transcriptional level. Therefore, it appears that the rate of production of DHFR mRNA is controlled by different biochemical mechanisms when cells are in different physiological states.

Animals↗

Incidence of beta hemolytic streptococcal pharyngitis in adolescent with infectious mononucleosis.

Reports on the incidence of beta-hemolytic group A streptococci (BHGAS) in the pharynx of patients with infectious mononucleosis (IM) have varied from 3% to 33%. To ascertain the rate of infection, we prospectively performed serial throat cultures and determined anti-streptococcal antibody titers on 45 students with confirmed IM by Epstein-Barr virus-specific serology. One hundred healthy control students had throat cultures for comparison. The rate of recovery of BHGAS was similar in patients with IM (4%) and controls (3%). No students with IM had a fourfold rise of anti-streptococcal antibodies. We conclude that routine culture for BHGAS and/or treatment with antibiotic agents is not indicated in all patients with IM.

Adolescent↗

Immunomodulation and antitumor effects of MVE-2 in mice.

The biological response modifier maleic anhydride-divinyl ether (MVE-2) can activate natural killer (NK) cells and macrophages and can act as an immunoadjuvant for T and B cells. MVE-2 activates macrophages following intravenous or intraperitoneal injection in a compartmentalized manner, i.e., peritoneal macrophages (i.p. injection) or alveolar macrophages (i.v. injection). It activates NK cells in vivo but not in vitro, a dichotomy that may be secondary to interferon production. Splenic NK cell activity is not prolonged by the multiple injection of MVE-2; instead, it induces a state of NK cell hyporesponsiveness, which may limit its therapeutic efficiency. Therapeutic properties of MVE-2 are largely limited to nonspecific immunoprophylaxis, which may be associated with NK cell activation but which does not necessarily correlate with the level of splenic NK cell activation. Minimal therapeutic efficiency consisting of a slight prolongation in survival is observed in mice with preexistent disease treated with MVE-2. Prolonged survival is observed only in those animals placed on therapy soon after tumor cell challenge (experimental metastasis) and not in mice with established spontaneous metastasis. The need to manipulate the animal model (MVE-2 injection prior to or rapidly following tumor challenge) seems to predict that this agent is unlikely to be clinically useful against preexistent metastatic tumor burden, although some efficiency may be associated with local treatment into the pleural or peritoneal cavity.

Adjuvants, Immunologic↗

Comparison of antibody isotypes in sera and circulating immune complexes during tumor growth and metastasis of three tumor models in mice.

The sera and circulating immune complexes (CICs) from mice bearing either UV-2237 mm, K-1735 M2, or B16-BL6 were analyzed for antibody isotype distribution during primary tumor growth and spontaneous metastasis. These studies clearly demonstrate that elevated CIC concentrations parallel the initial stages of primary tumor growth; however, the CICs, as well as serum concentration of all immunoglobulin G isotypes, rapidly decrease to near normal levels in the presence of heavy tumor burden. Following resection of the primary footpad tumor, increases in CIC levels paralleled outgrowth of metastasis; however, the antibody content of the CICs was isotypically restricted to immunoglobulin G2b and immunoglobulin G3 regardless of the tumor type. The immunoglobulin G isotype content of the CICs did not correspond to elevations in the serum concentrations of each respective isotype during neither primary nor metastatic tumor growth. This serial study indicates that the use of non-antigen-specific assays for CICs without regard to tumor burden or possible antibody isotypic restriction may be misleading, and that CIC levels can indeed correlate with metastatic tumor burden.

Animals↗

Alterations in phosphofructokinase isoenzymes during early human development. Establishment of adult organ-specific patterns.

Human 6-phosphofructokinase (EC 2.7.1.11) exists in tetrameric isoenzymic forms composed of muscle (M), liver (L) and platelet (P) subunits, which are under separate genetic control. In the adult, the proportion of these subunits in different organs reflects the relative activity of glycolysis versus gluconeogenesis. To elucidate the developmental basis for the observed distribution, we investigated the isoenzymic transitions of phosphofructokinase in human foetuses (12-40 weeks' gestation) by using high-resolution chromatography and monoclonal antibodies. We studied skeletal muscle, heart, liver and brain because these organs show very different glycolytic fluxes and isoenzymic patterns in adult individuals. Our results demonstrate that there is no unique 'foetal' form of phosphofructokinase in humans, but all three loci are variably expressed in all foetal organs during early gestation. As development proceeds, muscle and liver isoenzyme patterns show dramatic changes, with disappearance of P and L subunits in muscle and transient reappearance of M and P subunits in liver; in contrast, phosphofructokinase isoenzymes change little in brain and heart. Most changes occur at mid-gestation and near term, and adult isoenzyme patterns are expressed at birth, indicating that organ differentiation is complete. These studies show that phosphofructokinase undergoes changes of isoenzyme patterns similar to, but not identical with, those of other multilocus isoenzyme systems of glycolysis. The observed changes probably reflect changing patterns of gene expression, with repression of some loci and activation of others.

Brain↗

Molecular aspects of growth factor action: receptors and intracellular signals.

An increasing number of factors have been described which influence the proliferative responses of normal and neoplastic cells. A review of such moieties, their occurrence and possible mechanisms of their action and interaction is presented together with a discussion of their potential importance in the genesis and progression of neoplasms.

Animals↗

An inhibitory effect of tumour promoters on human epithelial cell growth can be dissociated from an effect on junctional communication.

Studies with rodent cells have indicated that the abilities of various tumour promoters to inhibit metabolic cooperation correlate with their potencies as mitogens. Here we have examined the effects of the most potent phorbol ester tumour promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), on metabolic cooperation and growth of human epidermal cells transformed by SV40 (SVK14 cells). In this system, TPA inhibits junctional communication and at the same concentration also inhibits growth in a reversible fashion. These effects appear to be mediated by binding of phorbol ester to a single class of high affinity binding site with a Kd similar to that reported for rodent cells (Kd = 20.9 nM at 4 degrees C). Further studies on the effects of phorbol esters on other human epithelial cell lines reveal that the inhibitory effects of TPA on growth and metabolic cooperation may be completely dissociated. Alternative mechanisms by which TPA may exert its growth-inhibitory effects are discussed.

Breast Neoplasms↗

Interdisciplinary model for the inpatient treatment of adolescents with anorexia nervosa.

This paper describes the inpatient phase of an anorexia nervosa treatment program in an adolescent unit of a children's hospital. This program focuses on four goals: improving eating behavior, improving socialization, achieving initial weight gain, and engaging the patient and her family with an outpatient psychotherapist. The patients were divided into three groups according to severity. All five Group I patients (less than 25% body weight loss) had a composite 100% achievement of the four goals. Twenty out of 21 Group II patients (greater than 25% body weight loss) had 100% achievement of the four goals. Three out of six Group III patients (greater than 25% body weight loss and requiring hyperalimentation) had 100% achievement of the four goals. The success of this inpatient program is felt to be due to the pediatric-psychiatric collaboration, the involvement of the family during the inpatient phase, the therapeutic use of an interdisciplinary team and of the social system of the inpatient unit including other patients and recreation therapist.

Adolescent↗

Potentially life-threatening hypophosphatemia in anorexia nervosa.

An anorexia nervosa patient with hypophosphatemia secondary to starvation and laxative abuse is reported. During the course of refeeding by tube with a high caloric balanced formula, the patient's serum phosphorous dropped from low normal on admission (2.7 mg/dl) to 0.4 mg/dl aggravated by an overdose of laxative she had stolen from the medicine cart. This required ICU monitoring during intravenous phosphorous administration. This case points out the potential hazard of oral realimentation in a severely cachectic anorectic.

Adult↗