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Biomedical subjects

M D Kaufman

Publications and source records attributed to M D Kaufman.

10 recordsLinked to original sources
PubMed2000

Taxol and discodermolide represent a synergistic drug combination in human carcinoma cell lines.

Recently, three natural products have been identified, the epothilones, eleutherobin, and discodermolide, whose mechanism of action is similar to that of Taxol in that they stabilize microtubules and block cells in the mitotic phase of the cell cycle. In this report, we have compared and contrasted the effects of these new agents in Taxol-sensitive and -resistant cell lines. We also have taken advantage of a human lung carcinoma cell line, A549-T12, that was isolated as a Taxol-resistant cell line and found to require low concentrations of Taxol (2-6 nM) for normal cell division. This study then examined the ability of these new compounds to substitute for Taxol in sustaining the growth of A549-T12 cells. Immunofluorescence and flow cytometry have both indicated that the epothilones and eleutherobin, but not discodermolide, can substitute for Taxol in this Taxol-dependent cell line. In A549-T12 cells, the presence of Taxol significantly amplified the cytotoxicity of discodermolide, and this phenomenon was not observed in combinations of Taxol with either the epothilones or eleutherobin. Median effect analysis using the combination index method revealed a schedule-independent synergistic interaction between Taxol and discodermolide in four human carcinoma cell lines, an effect that was not observed between Taxol and epothilone B. Flow cytometry revealed that concurrent exposure of A549 cells to Taxol and discodermolide at doses that do not induce mitotic arrest caused an increase in the hypodiploid population, thereby indicating that a possible mechanism for the observed synergy is the potentiation of apoptosis. Our results suggest that Taxol and discodermolide may constitute a promising chemotherapeutic combination.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Gram-scale synthesis of (+)-discodermolide.

[formula: see text] A triply convergent, highly efficient second-generation synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on a 1-g scale.

Alkanes↗
PubMed1998

Do microbes with peptides mimicking myelin cause multiple sclerosis if the T cell response to their unique peptides is limited?

This hypothesis for the pathogenesis of multiple sclerosis is based upon assumptions about the response of the T cell repertoire to pathogens. Immunologic and epidemiologic observations of several conditions suggest that activation of T cells formed in early life mediate injury to the central nervous system. Early in life, selection of lymphocytes by the thymus produces a weakly autoreactive T cell repertoire which, with the help of transient maternally-derived defenses, recognizes pathogens. These responses later are supplemented by pathogen-specific responses, acquired as microbes are encountered. As the thymus involutes, the diversity of pathogen-specific responses to microbial epitopes is progressively fixed. Reduced and delayed pathogen exposure, common in developed societies, limits the repertoire of memory T cells, which can efficiently eliminate pathogens. Due to their small number, pathogen-specific lymphocytes which mature extrathymically may not be able to rapidly eliminate most pathogens, and without the editing of the thymus, they may be autoreactive. In this setting, novel pathogens with epitopes mimicking myelin may elicit a T cell response which is autoreactive. Peptides of common microbes are known to activate T cells recognizing dominant antigens of myelin. It is postulated that at the equator, intense, non-seasonal encounters with microbes elicit an immune repertoire that produces resistance to autoimmunity, while, in temperate climates, moderate, seasonal exposures increase susceptibility to it. The differences in responses to microbes between populations with a low or high prevalence of multiple sclerosis suggests that T cell repertoires are divergent in these groups. An exuberant innate response, postulated to diminish as the load of enteric microbes falls and sanitation improves in relation to the distance from the equator, may increase resistance to multiple sclerosis by eliminating the need for T cell activation. Human herpesvirus-6 and respiratory syncytial virus are possible prototypes of microbes which activate myelin-directed T cells.

Antigens, Viral↗
PubMed1994

Radiation and MS.

Explore the source record for details and available documents.

Brain Neoplasms↗
PubMed1992

Conjugal MS.

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Female↗
PubMed1988

Paroxysmal unilateral dysosmia: a cured patient.

A 31-year-old woman with an 11-year history of unilateral paroxysmal olfactory hallucinations was cured by resection of the homolateral olfactory bulb, which was believed to be the site of origin of the noxious smell.

Adult↗
PubMed1981

Progressive sensory neuropathy in patients without carcinoma: a disorder with distinctive clinical and electrophysiological findings.

Seven patients with severe progressive impairment of kinesthetic sense, mild dysfunction of cutaneous sense, and sparing of motor function were examined during a 3-year period. The clinical and electrophysiological findings are described in detail. None of these seven has had evidence of cancer despite a thorough investigation and a 3- to 16-year (average, 7 years) period of symptoms. These patients' symptoms were indistinguishable from those of patients with sensory neuropathy and coexistent carcinoma, suggesting that progressive sensory neuropathy is not invariably associated with carcinoma.

Adult↗
PubMed1980

Masticatory spasm in facial hemiatrophy.

Spontaneous spasms began in the left masseter muscle six years following the onset of facial hemiatrophy in a young woman. A dental procedure had preceded the original facial wasting by four weeks. The electromyographic findings were similar to those described in hemifacial spasm and consisted of brief bursts of one to four morphologically different potentials, each firing at rates of up to 200 Hz. The findings demonstrate that spontaneous activity due to nerve injury can arise in muscles innervated by the trigeminal nerve.

Adult↗