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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 631 records · Page 35Linked to original sources

Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection.

H-2 gene transfection was used to restore expression of H-2K antigens in metastatic and non-metastatic subclones of a murine fibrosarcoma that lack their major histocompatibility complex-encoded H-2K antigens. De novo expression of H-2K reduced tumorigenicity and abolished the formation of metastasis in syngeneic mice. Expression of H-2K may lead to effective recognition of the disseminating tumour cells by the host immune system.

Animals↗

Association of phosphorylation of the T3 antigen with immune activation of T lymphocytes.

In human T lymphocytes the antigen receptor (Ti) is associated non-covalently on the cell surface with the invariant T3 antigen which comprises 3 chains: two glycosylated polypeptides of relative molecular mass 26,000 (Mr 26K) and 21K (gamma and delta) and one non-N-glycosylated polypeptide of Mr 19K (epsilon). The proposed function of T3 is to transduce the activation signals delivered via the antigen receptor. Recently we have shown that phorbol esters, which stimulate protein kinase C, can induce phosphorylation of the gamma subunit of the T3 antigen. But the critical question is whether T3 phosphorylation occurs as a normal consequence of immune activation of T lymphocytes. In this respect, it has been shown that immune stimulation of murine T cells results in phosphorylation of Ti-associated polypeptides that may be the functional analogues of the human T3 antigen. We have therefore monitored T3 phosphorylation after exposure of human T cells to antigen or phytohaemagglutinin (PHA). The data show that both stimuli initiate phosphorylation of the gamma subunit of the T3 antigen which indicates that T3 phosphorylation is a physiological response to immune activation.

Antigens, Differentiation, T-Lymphocyte↗

Neonatal pyoscrotum and perforated appendicitis.

Neonatal appendicitis is so unusual that is has been considered nonexistent. We present the case of a 6 day old male with acute scrotal swelling who was found to have a perforated appendicitis inside a hernia sac. A literature review supports the impression that neonatal appendicitis is rare; however, when it occurs inside a hernia sac, it has a good prognosis.

Appendicitis↗

Anti-tumor vaccination in heterozygous congenic F1 mice: presentation of tumor-associated antigen by the two parental class I alleles.

Peptide vaccination of homozygous mice against syngeneic tumors using single major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocyte (CTL) epitopes elicits effective immune responses against metastatic growth. So far, single-peptide vaccination of patients against their autologous tumors seems to elicit less satisfactory results. In this study, the authors tried to determine whether effective anti-metastatic immunity requires the presentation of peptides restricted by the two parental class I major histocompatibility complex alleles in heterozygous hosts. The immune response against the H-2b-derived 3LL Lewis lung carcinoma was evaluated in heterozygous recombinant congenic F1 mice (Kk x K(b)) and (Kd x K(b)). Vaccination of such heterozygous animals with dendritic cells expressing the two parental H-2K alleles, pulsed with total tumor extract, elicited a potent anti-metastatic response. A comparable response was obtained after vaccination with tumor cells genetically modified to express the two class I alleles. In contrast, vaccination of the heterozygous mice with dendritic cells expressing only one of the parental F1 H-2K alleles or with tumors expressing only one H-2K allele failed to elicit effective immunity against tumor metastasis in recombinant congenic F1 mice. It appears, therefore, that to achieve effective anti-metastatic immunotherapy in heterozygous organisms, presentation of cytotoxic T lymphocyte epitopes restricted by the two parental class I alleles is required.

Alleles↗

Combined ionizing radiation and thermal injury in the rat. Evaluation of early excision and closure of the burn wound.

The present study was undertaken to establish an animal model of combined whole-body irradiation and thermal injury and to determine the effectiveness of early excision and closure of the burn wound in such a model. Whole-body irradiation over a range of doses resulted in a predictable mortality rate, with an LD50/30 of 783 rad with 95% confidence limits of 737 and 823 rad. A controlled 10% body surface area full-thickness thermal injury resulted in no deaths in 30 animals. When combined with a standard nonlethal 10% thermal injury, varying doses of whole-body irradiation resulted in widely differing LD50/30 values in three separate cohorts of rats. Excision and closure of a 10% burn 24 hours after exposure to 200 rads did not improve survival. (J BURN CARE REHABIL 1990;11:42-5)

Animals↗

Manipulation of metastasis and tumour growth by transfection with histocompatibility class I genes.

Approximately 50% of fibrosarcomas induced with methylcholanthrene A were found to be defective in H-2 expression. In tumours which lack H-2K antigens, H-2 gene transfection was used to restore H-2K expression. The de novo expression of H-2K reduced tumorigenicity and abolished the formation of metastases in syngeneic mice. Expression of H-2K seems to render the tumour cells immunogenic and leads to effective recognition of the tumour cells by the host immune system.

Animals↗

H-2Kb transfection of B16 melanoma cells results in reduced tumourigenicity and metastatic competence.

The metastatic B16 mouse melanoma shows a low cell surface expression of H-2Kb and H-2Db class I antigens on cells of both the high-metastatic line B16-F10 and the low-metastatic line B16-F1. Similarly, newly generated clones of these lines, having different metastatic properties, all express low levels of major histocompatibility antigens. One of these clones, the high-metastatic F10.9, was transfected with H-2Kb genes to generate H-2Kb-expressing transfectants. The resulting clones showed reduced tumourigenicity and a low metastatic phenotype. Unlike the parental cells, H-2Kb-positive transfectants are potent inducers and sensitive targets of H-2Kb-restricted syngeneic cytotoxic T cells. Immunization of mice with H-2Kb-positive transfectants conferred protection against a subsequent challenge with Kb-positive transfectants but had only a small effect on growth and metastatic spread of parental cells.

Animals↗

Effects of cutaneous aspirin on the human stomach and duodenum.

Oral aspirin blocks cyclooxygenase in platelets, lowering serum thromboxane concentrations. Oral aspirin also blocks cyclooxygenase in the gastrointestinal mucosa, lowering prostaglandin production and increasing the risk of gastrointestinal ulceration and bleeding. Aspirin placed on the skin also inhibits cyclooxygenase in platelets, but aspirin absorption through skin is slow, which may minimize the gastrointestinal effects. Our objectives in this study were 1) to compare the pharmacokinetic and pharmacodynamic effects of cutaneous and oral aspirin in healthy volunteers and 2) to compare the effects of cutaneous aspirin on gastroduodenal mucosal prostaglandin E2 and F2 alpha content and on mucosal damage, using endoscopy. The bioavailability of cutaneous aspirin was 4%-8% that of oral aspirin. Cutaneous aspirin (750 mg/day for 10 days) significantly lowered serum thromboxane (by 85%) and gastric and duodenal prostaglandins (by 49%-71%); placebo had no effect. Moreover, cutaneous aspirin, but not placebo, resulted in significant gastric mucosal injury. These findings demonstrate that even tiny amounts of aspirin in the blood (2 microM) have inhibitory effects on prostaglandin production in the human stomach and duodenum that result in gastric mucosal damage, even without direct exposure of the stomach to aspirin.

Administration, Cutaneous↗

Local adenovirus-mediated delivery of hirudin in a rabbit arterial injury model.

UNLABELLED: Intravascular delivery of an E1/E3 deleted adenovirus encoding the hirudin protein reduces neointimal formation in the rat arterial injury model. Given the interspecies variability in response to adenoviral vectors, we tested this same construct in the hirudin-sensitive cholesterol-fed rabbit arterial balloon injury model. We hypothesized that local delivery of an E1/E3-deleted adenovirus encoding hirudin (Ad-Hir) in addition to early hirudin infusion would limit neointimal formation compared to early hirudin alone. METHODS AND RESULTS: Local delivery of Ad-Hir, 2.5 x 10(10) PFU/ml, using a double balloon catheter [n = 6 vessels (v)] produced a 79% reduction in vessel wall thrombin activity at 48 h after balloon angioplasty (BA) compared with vehicle (Veh, n = 6v; p = 0. 05). In chronic experiments, hypercholesterolemic rabbits underwent femoral BA, and received either early hirudin alone (n = 9v) or early hirudin plus locally delivered Ad-Hir (early hirudin + Ad-Hir; n = 9v), an E1/E3-deleted adenovirus encoding beta-galactosidase (early hirudin + AdGal; n = 7v), or Veh (early hirudin + Veh; n = 10v). Early hirudin + Ad-Hir did not limit the arterial response to injury versus the other groups at 4 weeks after BA. Plaque area, cross-sectional luminal area narrowing by plaque, and T cell infiltration were significantly increased in the adenovirus- versus non-adenovirus-treated arteries. Plaque area correlated with T cell density. CONCLUSION: Following BA in cholesterol-fed rabbits, local transduction with A-Hir produced a marked reduction in vessel wall-associated thrombin activity. However, this strategy increased rather than decreased the arterial response to BA injury. Our results suggest that the lack of therapeutic effect resulted from adenovirus-stimulated plaque formation, possibly resulting from a T cell-mediated inflammatory response.

Adenoviruses, Human↗

A syngeneic metastatic tumor model in mice: the natural immune response of the host and its manipulation.

The cell-mediated immune response against a transplantable syngeneic metastatic solid tumor in mice was studied. The immune reactivity of spleen cells from tumor-bearing mice was found to vary during development of the tumor. For about a week after tumor transplantation, the spleen cells were able to protect recipient mice against challenge with tumor cells. Subsequently, the protective activity was replaced by an enhancing activity. Recipient mice that received tumor cells together with spleen cells from mice bearing tumors for about two or three weeks had a higher incidence of tumor takes and larger tumors than controls. This enhancement of tumor development was correlated with the size of the local tumor or metastases in the donors. The enhancing activity was found to be mediated by T lymphocytes and appeared to suppress the protective immune response of the recipients. We devised a system to strengthen the immune response of the host against the development of tumor metastases. In the tumor model used, removal of the local tumor after s.c. transplantation failed to prevent the development of lung metastases and death in most of the mice. However, syngeneic spleen cells which had been sensitized in vitro against tumor cells were found to serve as immunotherapeutic agents. Injection of such spleen cells into mice from which primary tumor implants had been removed surgically led to a markedly increased survival. Spleen cells from both normal and tumor-sensitized donors were effective, but splenocytes from mice bearing large tumors did not reduce metastatic development after sensitization in vitro. Thus, protection against the development of lethal metastases can be achieved with certain types of lymphocytes sensitized in vitro.

Animals↗

[Relation between patient's subjective complaints and family reports in patients with Alzheimer's type dementia].

INTRODUCTION: Reduced ability to remember facts and events of everyday life is a common complaint in the elderly and is also the first sign of Alzheimer's disease (AD). The present research was designed to study the interrelationship between severity of memory complaints (MC), informant report, and performance in memory tests. MATERIAL AND METHODS: Seventy three (73) patients (41 age associated memory impairment (AAMI), and 32 Alzheimer's disease) and 30 normal controls were studied using the Subjective Memory Questionnaire (modified version), an objective memory battery and the Hamilton depression scale. RESULTS: Age Associated Memory Impairment subjects reported more severe MC (p< 0.001). No relationship was found between severity of MC and age, sex or educational level. Patient's MC didn't correlate with objective memory battery. A strong correlation was found with Hamilton depression score. Caregiver memory reports correlated with objective memory performances. CONCLUSION: Depressive features in AAMI and anosognosia in dementia patients would explain these results. These data suggest that informant report is the best predictor of patient's memory performance.

Aged↗

[Musical memory preserved in an amnesic syndrome].

INTRODUCTION: In amnesic syndromes, it's usually to see dissociation between episodic, semantic and procedural memory. However, a few reports have been found about musical memory's processing and the relation with classic memory systems. AIM: To describe the musical's abilities preserved in a patient with amnesic syndrome and discuss possible neuropsychological and neurobiological bases implicated. CASE REPORT: A 28-years-old woman presenting with amnesic syndrome is reported. Following a carbon monoxide encephalophaty and subsequent hypoxia she remained in coma for 10 days with evidence of bilateral temporal changes, mainly affecting basal ganglia areas. The patient showed anterograde amnesia and semantic memory impairment, with disproportionately spared musical abilities' performance, either music perception (discrimination and recognition of tonal melodies, musical sight-reading) or music production (song and instrumental performance) or musical memory. CONCLUSIONS: This case suggests that the music require elaborate bihemispheric processing and may implicate different forms of information processing. The neural network involved in musical memory can be different that the declarative memory systems (episodic and semantic).

Adult↗

Cytotoxic and proliferative effect of tobacco products on Lewis lung adenocarcinoma cells and spleen lymphocytes.

The effect of tobacco products (TP) on the proliferation of lung adenocarcinoma cells (3LL) and mice spleen lymphocytes as well as on tumor growth and metastasis was analyzed. High concentrations of cigarette smoke condensate (CSC) or tobacco extract (TE) were cytotoxic for tumoral and lymphoid cells; in contrast smaller amounts of TP increased thymidine incorporation in both cell types. Lymphocytes were more susceptible to the toxic effect of TP than 3LL cells. When CSC or TE were mixed with 3LL cells and then inoculated into mice, they did not modify either the size of the local tumor induced by 3LL cells, or the number or appearance time of lung metastasis, although there was an increase in spleen weight.

Adenocarcinoma↗

Plantar approach for excision of bilateral soft tissue masses in a child.

A painful soft tissue mass of the plantar aspect of both feet, in a 5-year-old child, is presented. Plantar incisions are ideal in specific cases as long as the surgeon adheres to certain principles, as outlined in this manuscript. A discussion of lipomas is also presented. Optimum exposure is the key to total eradication of soft tissue lesions and to proper maintenance of wound healing. Location of the lesion presented warranted use of the plantar approach. Minimal hypertrophy of the plantar scar was achieved, as well as few symptoms by the patient.

Child, Preschool↗