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M J Cameron

Publications and source records attributed to M J Cameron.

35 records · Page 2Linked to original sources
PubMed1996

Direct transfer of a foreign MHC gene into human melanoma alters T cell receptor V beta usage by tumor-infiltrating lymphocytes.

The direct introduction of foreign genes into tumors shows promise as a therapeutic modality to enhance tumor immunogenicity. Hence, melanoma nodules were directly injected with a vector encoding an allogeneic MHC class I molecule, HLA-B7. Tumor-infiltrating lymphocytes (TIL) were isolated from cutaneous melanoma biopsies before and after HLA-B7 gene transfer. TIL were expanded in interleukin-2 (IL-2) by standard techniques for approximately 4 weeks, then analyzed for T cell receptor V beta usage by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Prior to gene transfer. TIL V beta usage was found to be highly restricted, the only one to four V beta families being expressed and one or two of these families representing more than 90% of the repertoire. As anticipated, TIL V beta usage varied among patients expressing different HLA types. However, V beta 13 was over-represented in that six of eight patients utilized V beta 13 as a dominant family, regardless of HLA type. Following HLA-B7 gene transfer, TIL V beta usage was markedly altered: (1) V beta families that dominated following gene transfer differed from the V beta families utilized by TIL prior to treatment, and (2) introduction of the HLA-B7 gene resulted in a more diverse repertoire with an increase in the number of V beta families represented. In two patients, TIL were evaluated before treatment and from multiple, distinct melanoma nodules following gene transfer. In these two patients, a comparison was made between TIL V beta profiles obtained after treatment from nodules that had been injected with the HLA-B7 gene or left untreated. Interestingly, the V beta repertoires of TIL from uninjected nodules following gene transfer were similar to that of TIL from injected nodules, rather than pretreatment TIL. These data demonstrate a direct immunological effect of foreign MHC gene transfer into human melanoma, and suggest that local expression of an allogeneic MHC molecule generates systemic alterations in the antitumor immune response.

CD4 Antigens↗
PubMed1995

Efficient transduction of early passage human melanoma to secrete IL-4.

Augmentation of tumor immunogenicity has been increasingly studied as a strategy to develop host immunity against established malignancies. Genetic modification of tumors to secrete immunoregulatory peptides such as IL-4 has been demonstrated to augment tumor immunogenicity and enhance the induction of tumor reactive lymphoid cells in animal models. To explore the ability of IL-4 to augment the immunogenicity of melanoma cells, we constructed a recombinant retrovirus vector encoding for human IL-4 and used it to transduce human melanomas. After optimizing retrovirus transduction conditions using a reporter virus, an IL-4 encoding retrovirus vector was used to transduce early and late passage melanoma cells. IL-4 production rates of up to 2000 pg/ml per 24 h per 10(6) cells were achieved, and provirus could be detected by Southern blot of the transduced cells at 0.1 copies per cell. The IL-4 produced by the melanoma cells was biologically active. Irradiated transduced melanoma cells continued to produce IL-4 for at least two weeks of observation. Thus melanoma cells can be efficiently modified to secrete biologically active IL-4, and may be suitable substrates for autologous tumor cell vaccines.

Cryopreservation↗
PubMed1995

Generation of therapeutic T-lymphocytes after in vivo tumor transfection with an allogeneic class I major histocompatibility complex gene.

In an effort to enhance the generation of tumor-reactive T-lymphocytes for adoptive immunotherapy, we examined the effects of in vivo transfection of an allogeneic major histocompatibility complex (MHC) class I gene (H-2Ks) of the poorly immunogenic B16BL6 (BL6) melanoma of H-2b origin. Cells from lymph nodes (LNs) draining these tumors after transfection were assessed in adoptive immunotherapy experiments for tumor reactivity after sequential activation with anti-CD3 monoclonal antibody (mAb) followed by culture in interleukin (IL)-2. H-2Ks lipofection of progressively growing BL6 subcutaneous tumors did not reduce tumorigenicity. However, in vivo lipofection of BL6 by intratumor inoculation or admixture of H-2Ks cDNA/liposome complexes and tumor cells prior to inoculation resulted in enhanced development of sensitized T-lymphocytes in the draining LN, which mediated the reduction of the numbers of established 3-day parental lung metastases in six of six experiments. In subsequent studies, in vivo transfection of BL6 with naked H-2Ks cDNA was found to be more effective than lipofection in eliciting sensitized T-cells in the draining LN. Admixture of liposomes alone or control plasmid DNA did not have an adjuvant effect similar to H-2Ks cDNA. Relative tumor transfection efficiency was assessed by an indirect assay with the chloramphenicol acetyltransferase (CAT) reporter gene. BL6 tumors were more efficiently transfected by intratumor inoculation with naked cDNA compared with lipofection. In summary, in vivo allogenization of the poorly immunogenic BL6 tumor resulted in enhanced generation of therapeutic T-cells effective in the treatment of parental tumor.

Adjuvants, Immunologic↗
PubMed1995

A phase II trial of interleukin-2 and interferon-alpha in the treatment of metastatic colorectal carcinoma.

A total of 29 patients with stage IV colorectal cancer were entered into a phase II trial of bolus interleukin-2 (IL-2) and interferon-alpha (IFN alpha) (3 x 10(6) U/m2 of each cytokine given i.v. q8h x 15 doses and repeated in 2 weeks). Immunologic parameters measured on isolated peripheral blood lymphocytes revealed increased activated T cells with upregulated natural killer and lymphokine-activated killer activity. Among 24 evaluable patients, there were 4 partial responses (17%) of short duration ( < or = 6 months). Three of the responding patients had been refractory to prior chemotherapy. Overall median survival in the 24 evaluable patients was 18.5 months. Therapy necessitated an inpatient setting, with the most common toxicities being hypotension, hepatic insufficiency, fever, hypocalcemia, nausea/vomiting, and renal insufficiency. There were two treatment-related deaths. Because neither IL-2 nor IFN alpha alone has significant activity against colorectal cancer, the responses observed in this study suggest a potential synergistic effect between the two cytokines. However, the toxicity and short duration of response without survival benefit do not support the routine use of this regimen as a therapeutic modality for this tumor histology.

Adult↗
PubMed1995

Beyond consequences.

Explore the source record for details and available documents.

Activities of Daily Living↗
PubMed1994

Application of flow cytometry to determine the cytotoxicity of urethane dimethacrylate in human cells.

The effects of an oligomer, urethane dimethacrylate (UDMA), on two human cell lines were studied using flow cytometry (FCM). Untreated and treated cultures of propidium iodine-stained KB (epidermal oral carcinoma cells) and human foreskin fibroblast (HFF) cells were analyzed for cellular DNA content. Concentrations of 10 and 25 microM of UDMA slightly perturbed the KB cell cycle progression at 24 and 48 h of incubation. However, the effect of 50 microM was more pronounced at the latter incubation time period. In cell growth experiments, the sublethal concentrations (10 and 25 microM) produced inhibition of KB cell growth rate at a moderate level, which resulted in the prolongation of cell population doubling time. Significant inhibition of cell growth occurred when 50 microM (lethal concentration) was used. Data obtained from the cell cycle perturbation analysis, evidenced by FCM, correlated with the extent of inhibition in KB cell growth rates. The effects of sublethal concentrations were reversible during a 24 h period of oligomer withdrawal from culture medium. In contrast, the effects of 50 microM were not reversible. In HFF cells the depletion of S phase in the cell cycle was the major effect of 50 microM of UDMA. It was concluded that FCM technology is an ideal and practical approach for studying the cytotoxicity of components of dental composites.

Carcinoma↗
PubMed1994

Behavioral medicine treatment of ruminative vomiting and associated weight loss in an adolescent with autism.

Treated persistent ruminative vomiting of a 15-year-old boy with autism using a multicomponent behavioral medicine program within a residential facility. Preceding intervention the boy had lost 15 pounds associated with high-rate ruminating. The treatment program included a combination of dietary, nutritional, and behavioral procedures that emphasized food restrictions, satiation, and setting condition manipulations. Ruminative vomiting was reduced to near-zero levels and weight gain was achieved following treatment implementation. These therapeutic gains were sustained during a maintenance programming phase and at 1- through 4-month follow-up assessments. Issues related to functional assessment and treatment formulation in behavioral medicine intervention for ruminative vomiting are discussed.

Adolescent↗
PubMed1993

Clinical observations on adoptive immunotherapy with vaccine-primed T-lymphocytes secondarily sensitized to tumor in vitro.

The adoptive immunotherapy of human malignancy requires reliable methods to sensitize and expand patients' T-cells reactive to autologous tumors. In animal studies, we have generated therapeutic effector cells against a poorly immunogenic tumor by a two-step procedure: vaccination of the host followed by the secondary stimulation of vaccine-primed lymph node (LN) cells by in vitro sensitization (IVS) with tumor in the presence of interleukin 2 (IL-2). Based on these observations, we performed a clinical trial in patients with advanced cancer to evaluate the antitumor efficacy of vaccine-primed LN cells which were similarly activated in vitro. Patients were vaccinated with irradiated autologous tumor admixed with Bacillus Calmette-Guérin and had draining LN excised 10 days later for IVS culture. During IVS culture, LN cells expanded up to 14-fold (average of 8.4-fold). A mean of 6.7 x 10(9) cells was infused in ten patients (seven melanoma, three renal cell cancer) along with the concomitant i.v. administration of IL-2 (180,000 IU/kg every 8 h for 5 days). Phenotype analysis of IVS-LN cells revealed 78 +/- 4% CD3+ T-cells which were predominantly CD4+ (67 +/- 5%) with expression of HLA-DR and IL-2 receptor. IVS-LN cells displayed relative specificity of autologous tumor lysis in four of ten cases compared to zero of seven IVS-peripheral blood lymphocytes derived from the same patients as measured by the 51Cr release assay. One mo after therapy, seven of nine patients treated with IVS-LN cells and IL-2 developed delayed-type hypersensitivity reactivity to autologous tumor compared to zero of nine patients treated with tumor vaccination and IL-2 only (P < 0.002). These observations suggest that antitumor reactivity was passively transferred with the IVS-LN cells. Major toxic side effects including fever, hepatic dysfunction, and weight gain associated with the capillary leak syndrome were associated with exogenous IL-2 administration. Tumor vaccination and cell transfer were well tolerated without significant complications. Of the ten patients treated with IVS-LN cells and IL-2, there were one partial and one minor response, and one patient has had stable disease for 27+ mo. There was no evidence of tumor response in ten patients treated with tumor vaccination and IL-2 only. Further clinical studies evaluating the antitumor reactivity of vaccine-primed LN cells are warranted.

Adult↗
PubMed1993

Generation of T-cells reactive to the poorly immunogenic B16-BL6 melanoma with efficacy in the treatment of spontaneous metastases.

The B16-BL6 (BL6) melanoma is a poorly immunogenic murine tumor that is highly invasive and spontaneously metastasizes from the primary site. Utilizing an established anti-CD3/interleukin-2 (IL-2) culture procedure, we have previously reported that lymph nodes (LNs) draining immunogenic murine sarcomas contained preeffector cells that could be activated to differentiate into therapeutic effector cells for adoptive immunotherapy. By contrast, LNs draining the poorly immunogenic BL6 melanoma were found not to be a reliable source of preeffector cells. Instead, sensitization of preeffector cells reactive to BL6 required the subcutaneous inoculation of tumor admixed with Corynebacterium parvum. LN cells draining these vaccination sites demonstrated therapeutic efficacy only after subsequent anti-CD3/IL-2 activation. The sensitization of preeffector cells was dependent on the presence of tumor antigen and an optimal dose of C. parvum (< or = 50 micrograms). Furthermore, kinetic analysis revealed that the preeffector response was transient after tumor vaccination. The therapeutic efficacy of anti-CD3/IL-2 activated LN cells was further evaluated in the treatment of spontaneous macroscopic BL6 visceral metastases. Spontaneous visceral metastases were induced in animals by inoculation with BL6 tumor in the footpad followed by amputation of the primary tumor 3 weeks later. The systemic transfer of 10(8) anti-CD3/IL-2 activated T-cells and the concomitant intraperitoneal administration of subtherapeutic doses of IL-2 1 week after amputation cured 50% of the animals and prolonged median survival time (MST) to > 140 days. All mice except one that received no treatment or was treated with IL-2 alone succumbed to visceral metastases with an MST of approximately 23 days. This study characterizes a model whereby the weak immune response to the BL6 melanoma can be positively or negatively modulated for the generation of antitumor reactive T-cells useful in adoptive immunotherapy.

Animals↗
PubMed1993

"We'll cross that hurdle when we get to it". Teaching athletic performance within adaptive physical education.

Persons with developmental and physical disabilities who are enrolled in educational programs often participate in adaptive physical education classes. Primarily, these classes are designed to provide individuals with the opportunity to develop their physical abilities. However, they can also serve as a training ground for the Special Olympics. Teaching the motor skills that are prerequisite to participation in many adaptive physical education and Special Olympics activities can be a formidable objective. This study demonstrates how a person with developmental disabilities was taught, by way of stimulus control shaping, the necessary motor skills to enable him to participate in the hurdling event at the Special Olympics.

Adult↗
PubMed1991

Self-help research and the public mental health system.

Discusses views of self-help leaders, researchers, and policy makers from the public mental health system about collaborative research with self-help groups. Topics include assumptions underlying collaborative research, barriers to collaborative research, and the potential benefits of collaborative research. Special attention is given to the rationale and methods for including minorities in self-help research. Initial discussions were held at a meeting convened by the NIMH-funded Center for Self-Help Research and Knowledge Dissemination at the University of Michigan.

Community Mental Health Services↗
PubMed1990

Macintosh graphics for the EPICS flow cytometer user.

Graphic options for the EPICS flow cytometer user have been restricted in the past to software written specifically for the analysis and graphics of flow cytometric data. The software is limited to only a few graphic presentation styles. The technique described will allow the EPICS user to translate histogram files into text files that can be used in an alternative computer format.

Computer Graphics↗
PubMed1986

Measurement by radioimmunoassay of prostaglandins as their methyl oximes.

Antisera have been raised to the following prostaglandins as their methyl oximes; PGE2, PGD2, 13-14-dihydro-15-oxo PGE2, 13,14-dihydro-15-oxo PGF2 alpha, 6-oxo PGF1 alpha, 6-oxo PGE1 and thromboxane B2. These antisera have good specificity and sensitivity and their use allows the immediate treatment of biological fluids with oximating solution which prevents sample decomposition during storage. A methyl oximating reagent is described which gives greater than 95% conversion of PGs to their methyl oximes by treating samples at 20 degrees C overnight. The use of this reagent allows easy and reliable sample derivatisation prior to assay with the above antisera. Since the antisera (with the exception of that for thromboxane B2) do not recognise the underivatised PG or the oxime (=NOH) form, oxime formation can be carried out in parallel with methyl oxime formation and the oximated portion of the sample can act as a "reference" for the methyl oximated portion, which will allow non specific interference to be recognised.

Antibody Specificity↗
PubMed1986

The stimulation of prostaglandin production by two antiprogesterone steroids in human endometrial cells.

Endometrial stromal cells and isolated endometrial glands obtained from women during days 6-26 of the ovarian cycle were cultured for 24 h in the presence of the progesterone antagonists 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-[1-propynyl] estra-4,9-dien-3-one (RU486) and 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl] 17 alpha-[3-hydroxy-1-propenyl]estra-4,9-dien-3-one (ZK 98734). Both steroids stimulated prostaglandin F2 alpha (PGF2 alpha) production by stromal cells in a dose-dependent manner, in doses ranging from 10-1000 nM. Progesterone (100 nM) inhibited RU486 stimulation, except at the highest dose of antiprogestin. PGE2 was produced in smaller amounts than PGF2 alpha, but, when measurable, it also increased in the presence of RU486. In contrast, RU486 did not increase PG production by endometrial glands. In an experiment to determine the effect of pretreatment, stromal cells were incubated for 24 h with 1000 nM progesterone or RU486 (all with 100 nM 17 beta-estradiol) with either 30 or 6 microM arachidonic acid. These six batches of cells were incubated for a second 24 h with either progesterone or antiprogestin. Cells pretreated with the higher dose of arachidonic acid had a marked increase in PGF2 alpha production during the second 24 h only when also pretreated with progesterone. This finding suggests that progesterone allows an accumulation of PG precursor in a suitable accessible pool. Pretreatment with progesterone also allowed a greater conversion of PG to its 13,14-dihydro-15-keto metabolite. These results suggest that antiprogesterone steroids may act as menstrual regulators by: stimulating endogenous PG production within the endometrial stromal cells and inhibiting PG catabolism.

Dinoprost↗
PubMedDate not supplied

Component analysis and stimulus control assessment of a behavior deceleration treatment package.

A treatment package that included two setting condition manipulations and visual occlusion was implemented to gain control over the high-intensity screaming and whining of a 16-year-old female with developmental disabilities. The study included an analysis of the individual and combined components of the treatment package and a stimulus control analysis of three salient features of the visual occlusion apparatus (i.e., opaque screen, secured helmet, and cranial pressure). Results showed that the treatment package occasioned a deceleration in the two targeted vocal behaviors and a reduction in the amount of time the participant was required to wear the occlusion apparatus. An analysis of the apparatus suggested that the critical element needed to control inappropriate vocalizations appeared to be cranial pressure, which was naturally produced by the helmet. Consequently, the helmet was eliminated and cranial pressure was produced by a woman's headband. Follow-up data, collected 1, 2, and 3 months after termination of systematic intervention, revealed near-zero levels of screaming and whining behaviors. A 9-month follow-up investigation involving the removal and subsequent reinstatement of the headband procedure supported the use of the headband for the maintenance of behavioral gains.

Adolescent↗
PubMedDate not supplied

Therapeutic efficacy of T cells derived from lymph nodes draining a poorly immunogenic tumor transduced to secrete granulocyte-macrophage colony-stimulating factor.

We examined the host immune response to the poorly immunogenic B16-BL6 melanoma, which was transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) (450 ng/10(6)/24 h). Tumor growth after subcutaneous inoculation was not significantly altered, although an influx of neutrophils and monocytes/macrophages was evident within tumors and draining lymph nodes (LNs). Immunization with irradiated transduced cells did not induce systemic immunity to the parental tumor. However, vaccination with transduced tumors significantly augmented in vivo sensitization of draining LN cells. These tumor-draining LN (TDLN) cells, when secondarily stimulated in vitro with anti-CD3 monoclonal antibodies and expanded in interleukin-2 (10 U/ml), exhibited greater release of GM-CST and interferon-gamma against tumor compared with TDLN cells from animals with parental tumor. In adoptive immunotherapy, activated LN cells draining transduced tumors mediated significant reductions of the numbers of established pulmonary metastases compared with LN cells draining parental tumor, which were ineffective. In addition, the therapeutic efficacy of LN cells draining transduced tumors was significantly better than LN cells primed in vivo with tumor cells admixed with Corynebacterium parvum, which we have previously described as an approach to generate immune cells. Thus, GM-CSF appears to be an important adjuvant in the induction of tumor immunity.

Animals↗