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Biomedical subjects

L Maron

Publications and source records attributed to L Maron.

17 recordsLinked to original sources
PubMed2002

Are the carbon monoxide complexes of Cp(2)M (M = Ca, Eu, or Yb) carbon or oxygen bonded? An answer from DFT calculations.

DFT calculations have been performed on the CO adducts of the bivalent lanthanides, Cp(2)M(CO)(x), where M is Eu or Yb and x is 1 or 2, the alkaline earth metallocene Cp(2)Ca(CO), and the methylisocyanide adducts of Yb. The calculated nu(CO) values are in agreement with experiment for Cp(2)M(CO) when M is Ca or Eu, but in striking disagreement when the CO is bound to the metal by way of the carbon atom in CO in the case of Yb. The calculated nu(CO) values for M = Yb are brought into agreement with experiment when the CO is allowed to bond to Cp(2)Yb by way of the oxygen atom.

Journal Article↗
PubMed2001

Relative shift in activity from medial to lateral frontal cortex during internally versus externally guided word generation.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p <.001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

Adult↗
PubMed2001

DFT study of H--H activation by Cp(2) LnH d(0) complexes.

The energy required to activate the H--H bond in the entire series of Cp(2)LnH complexes has been calculated by DFT (B3PW91) methods. The activation energies have been calculated to vary from 0.5 to 8.0 kcal x mol(-1), indicating an overall facile reaction. The electronegativity of the lanthanide in its most stable oxidation state is suggested to be a leading factor for interpreting the trends in activation energy. The geometry of the transition state is best viewed as an almost linear H(3)(-) ligand with short H--H distances and strong M--H interaction, through the wingtip H centers, with Ln. The exchange reaction is thus established to be a sigma bond metathesis reaction.

Journal Article↗
PubMed2000

Unilesional mycosis fungoides: a study of seven cases.

BACKGROUND: Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized by a solitary lesion clinically and by histopathological features indistinguishable from those of MF, and typically having a benign course. OBJECTIVE: To describe the clinicopathological features of a series of patients with unilesional MF. METHODS: The records of cases of unilesional MF identified during a 10-year period in two medical departments were reviewed. RESULTS: There were 7 patients: 6 males, 1 female; mean age at the time of diagnosis: 32 years; age range: 12-58 years; 3 were below the age of 18 years. The mean pretherapy follow-up period was 9 years (range: 2-20 years). In 5 patients, the eruption consisted of a characteristic patch or plaque of MF located on the trunk or upper extremity; in 2 it was atypical - in 1, a hypopigmented patch, and in 1, a plaque indistinguishable from MF-associated follicular mucinosis. Histopathologically all the lesions exhibited features characteristic of MF, with CD3+ lymphoid cells. In 6 cases (with available fresh frozen tissue) there was a predominance of CD3+ CD4+ cells; in 1 of 5 there was deletion of CD7, and in 3 of 5 there was an overexpression of IL-2 receptor. T-cell receptor gamma gene rearrangement was found in 1 of 4 cutaneous lesions tested; in 2 cases it was found in the blood but not in the skin. Treatment modalities included localized electron beam, excision, topical nitrogen mustard or topical steroids and sunbathing, resulting in all cases in a sustained complete clinical response. In 1 patient, however, there were 2 local recurrences and in yet another patient there was distant cutaneous spread 3.5 years after therapy. CONCLUSIONS: Unilesional MF is a rare variant of CTCL, has heterogeneous clinical manifestations and can affect any age group, including children. The histopathological and immunophenotypical features are in general indistinguishable from those observed in multilesional MF. Although it is a unifocal event, there may occasionally be cutaneous spread with the appearance of noncontiguous lesions, even a long time after therapy. Whether all cases represent minimal-stage IA MF or whether some are actually T-cell pseudolymphoma remains to be clarified.

Adolescent↗
PubMed1999

Left-hemisphere processing of emotional connotation during word generation.

Areas of the brain's left hemisphere involved in retrieving words with emotional connotations were studied with fMRI. Participants silently generated words from different semantic categories which evoked either words with emotional connotations or emotionally neutral words. Participants repeated emotionally neutral words as a control task. Compared with generation of emotionally neutral words, generation of words with emotional connotations engaged cortices near the left frontal and temporal poles which are connected to the limbic system. Thus, emotional connotations of words are processed in or near cortices with access to emotional experience.

Adolescent↗
PubMed1999

Follicular cutaneous T-cell lymphoma: a clinicopathological study of nine cases.

Nine patients with follicular cutaneous T-cell lymphoma (CTCL), a recently described variant of lymphoma, are presented. On the basis of clinical manifestations and disease course, three groups of patients were distinguished: (i) two patients with follicular CTCL not associated with conventional lesions of mycosis fungoides (MF) and showing no evolution towards MF in follow-up periods of 3 and 6 years; (ii) one patient with follicular CTCL that evolved into conventional MF within 3 years; (iii) six patients showing conventional MF lesions either before or concurrently with the follicular lesions and thus representing follicular CTCL of the true MF type. The follicular lesions included hair-devoid patches or plaques with spiky hyperkeratotic papules (four patients), keratosis pilaris-like lesions (four), comedo-like lesions (four), follicular papules with alopecia (three) and milia-like lesions (three). Histopathological examination showed perifollicular and intrafollicular lymphocytes, without mucin deposition and with minimal or no involvement of the overlying epidermis. Significant syringotropism was also observed in three cases. Immunohistochemical analysis showed the predominance of CD4 + T cells, deletion of CD7 in some cases, Ki-67 + lymphocytes confined mainly to the follicular epithelium, and expression of keratinocyte intercellular adhesion molecule-1 exclusively in the hair follicle. T-cell receptor gamma gene rearrangement was positive in the one case studied from each group. Different treatment modalities were employed, the most commonly used as monotherapy being phototherapy: psoralen ultraviolet A in four patients, two of whom showed a complete clinical and histopathological remission, and ultraviolet B in one patient, who showed a complete remission (both clinical and histopathological). This study indicates that follicular CTCL is more common than reflected in the literature, has heterogeneous clinical manifestations, and is either an expression of or closely related to MF. The influence of the follicular involvement on the therapeutic response remains to be clarified. However, our therapeutic experience clearly suggests that some patients with follicular CTCL can benefit from phototherapy.

Adult↗
PubMed1999

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Adult↗
PubMed1999

Differential expression of p53 and Ki-67 proteins in classic and iatrogenic Kaposi's sarcoma.

In many neoplasms, the finding p53 immunoreactivity correlates with striking cytologic atypia, a high tumor cell proliferation rate, and poor prognosis. The literature regarding p53 and Ki-67 (a nuclear proliferation-associated antigen) immunoreactivity in Kaposi's sarcoma is limited. We aimed to: (1) evaluate the role of p53 in the development of Kaposi's sarcoma; (2) determine whether there is a correlation between p53 and Ki-67 protein expression; and (3) determine possible differences between classical Kaposi's sarcoma, known usually to have a benign course, and iatrogenic Kaposi's sarcoma, the course of which is unpredictable, by studying the differential expression of p53 and Ki-67. Among 26 cases of classic KS and 19 of iatrogenic KS, 12 were classified histopathologically as early type and 33 as mixed or spindle-cell type. P53 and Ki-67 immunoreactivity correlated significantly with the histopathologic stage of KS (r=0.63, p=0.0001; r=0.42, p=0.0084, respectively). P53 was not detected in any of the cases in an early histopathologic stage but was present in 55% of the cases in a more advanced stage. The spindle cells increased in proportion with the histopathologic progression and were more often positive (p=0.019) and displayed more extensive staining than the endothelial cells (p=0.0001). There was a strong positive correlation between p53 and Ki-67 protein expression (r=0.43, p=0.0087). There was no correlation between the expression of either p53 or Ki-67 and the extent of the eruption. The expression of p53 and Ki-67 was significantly lower in iatrogenic cases than in the classic cases (p=0.009, p=0.0014, respectively), although no statistical difference was found between the histopathologic stages in the two clinical forms of KS. P53 immunoreactivity was detected in 79% of the cases of classic Kaposi's sarcoma in the mixed or spindle cell stage but in only 21.5% of the iatrogenic cases showing the same histopathologic stage (p=0.001), and the percentage of spindle cells as well as the endothelial cells expressing p53 was higher in the classic cases than in the iatrogenic cases (p=0.0032, p=0.0142, respectively). We conclude that p53 immunoexpression is a marker of tumor progression in classic Kaposi's sarcoma but not in most cases of iatrogenic Kaposi's sarcoma. The proliferative activity of the tumor cells in classic Kaposi's sarcoma is much higher than in iatrogenic Kaposi's sarcoma. Our work implies that the molecular steps involved in classic and iatrogenic Kaposi's sarcoma differ.

Aged↗
PubMed1997

Effect of the cytostatic butyric acid pro-drug, pivaloyloxymethyl butyrate, on the tumorigenicity of cancer cells.

Previously we have shown that pivaloyloxymethyl butyrate (AN-9), a pro-drug of butyric acid (BA), is a differentiation-inducing agent in a variety of cells. In this report, we demonstrate that AN-9 is a cytostatic but not cytotoxic agent in a myelomonocytic cell line (WEHI); thus, the cells were growth-arrested and differentiated. These late changes in the cells were preceded by changes in the expression of the early regulatory genes, c-myc and c-jun. Although initiation of all these events had already occurred after 1 h exposure to AN-9, the tumorigenicity of these cells tested in Balb/c mice was not affected. A marked reduction in the tumorigenicity of AN-9-treated cells was observed after 4 h of exposure. Exposure of the highly metastatic subclone of Lewis lung carcinoma (3LLD122) to AN-9 resulted in a very pronounced effect on the tumorigenicity of these cells tested in C57BL mice. Unlike WEHI cells, the tumorigenicity of 3LLD122 was almost completely diminished after 1 h of exposure. In both cell types a 10-fold higher concentration of BA did not affect the tumorigenicity of the cells as did AN-9.

Animals↗
PubMed1997

Butyric acid and pivaloyloxymethyl butyrate, AN-9, a novel butyric acid derivative, induce apoptosis in HL-60 cells.

A novel butyric acid derivative, pivaloyloxymethyl butyrate, AN-9, was previously shown to be a potent differentiating agent. AN-9 exerts a significant anticancer activity in vitro and in vivo. In all the activities examined, AN-9 was more potent than butyric acid. Here we show that AN-9 and butyric acid induce cell death by apoptosis. Exposure of HL-60 cells to butyric acid and AN-9 decreased cell numbers and induced cell differentiation and the appearance of typical apoptotic features. Induction of apoptosis and/or differentiation by AN-9 and butyric acid was dependent on the concentration and the time of exposure to the drugs. The advantage of AN-9 over butyric acid was further confirmed. Apoptosis induced by AN-9 occurred after a shorter exposure and at lower drug concentrations than that induced by butyric acid. Apoptosis by AN-9 was accompanied by reduction in Bcl-2 expression. Preincubation with antioxidants did not protect HL-60 cells from apoptosis induced by AN-9. HL-60 cells that were induced to differentiate by preincubation with retinoic acid or low AN-9 concentrations were more resistant to apoptosis, induced later by high concentrations of AN-9, than were undifferentiated cells.

Antineoplastic Agents↗
PubMed1993

1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer cells.

The effect of 1,25-dihydroxyvitamin D3 on lymphokine-activated killer (LAK) cells activity was studied. Treatment of LAK cells with 1,25-dihydroxyvitamin D3 for 24 h increased their cytotoxic activity without affecting cell proliferation. This effect was dose-dependent, detectable already at 10(-11) M attaining 44 +/- 7% increase at 10(-8) M. 1,25-dihydroxyvitamin D3 increased LAK cell content of the cytotoxic granule granzyme A by 21%. Secretion of granzyme A by LAK cells was triggered by 12-O-tetradecanoylphorbol 13-acetate and the calcium ionophore A23187. 1,25-dihydroxyvitamin D3 decreased the lag preceding secretion, increased the rate constant of exocytosis and the fraction of granzyme A cell content secreted. The potentiation of exocytosis was more pronounced at suboptimal calcium ionophore concentration suggesting that 1,25-dihydroxyvitamin D3 affects a calcium-dependent process. Since exocytosis of cytotoxic granules is a pivotal event in the killing of tumor cells by LAK cells, it is plausible that the enhancement of this process underlies the stimulation of LAK cell cytotoxic activity by 1,25-dihydroxyvitamin D3.

Analysis of Variance↗
PubMed1992

Responsiveness to 1,25-dihydroxyvitamin D3 is reduced in lymphocytes from osteoporotic women.

The purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25(OH)2D3 on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins. A group of 39 postmenopausal women, at least 10 years after the menopause, participated in the study. Osteoporosis, defined as the presence of at least one nontraumatic vertebral crush fracture, was diagnosed in 19 subjects. Mitogenesis of PBM cells stimulated by phytohemagglutinin and cultured for 72 h in the presence or absence of 1,25-(OH)2D3 (0.03-1 nmol/liter) was assessed by [3H]thymidine incorporation during a 4 h pulse. The maximal inhibitory effect of 1,25-(OH)2D3 at saturating concentration (1 nM/liter) was 74.6 +/- 2.8% (mean +/- SEM) for normal compared to 65.3 +/- 2.9% for osteoporotic women (P = 0.015). The geometric mean of the ED50 values of 1,25-(OH)2D3 was 60% higher in the osteoporotic than in the normal group (P = 0.035). Our data are consistent with the notion that reduced responsiveness of target organs to 1,25-(OH)2D3 is associated with osteoporosis.

Aged↗
PubMedDate not supplied

1,25-Dihydroxyvitamin D3 acts directly on human lymphocytes and interferes with the cellular response to interleukin-2.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) inhibits mitogen-induced lymphocyte proliferation in peripheral blood mononuclear cell preparations. Receptors for 1,25(OH)2D3 are present in monocytes and are acquired by lymphocytes upon activation. It is not clear whether the hormone inhibits lymphocyte mitogenesis by a direct action on the lymphocyte or only indirectly by affecting the regulatory monocytes. We addressed this question by using highly purified human lymphocyte preparations which contain less than 0.1% monocytes. 1,25(OH)2D3 inhibited the stimulation of purified lymphocytes by phytohemagglutinin and in the presence of fixed accessory cells, which cannot respond to 1,25(OH)2D3. The inhibitory effect attained 35% similar to that obtained in the presence of monocytes. 1,25(OH)2D3 inhibited interleukin 2 (IL-2)-driven stimulation of purified T cells in three different systems: cells treated with a submitogenic concentration of phytohemagglutinin, IL-2-dependent cells which bear receptors for IL-2 and naive cells in the absence of other mitogens. We conclude: (1) the human T lymphocyte is a direct target for 1,25(OH)2D3; (2) 1,25(OH)2D3 inhibits the response of activated, IL-2-receptor-bearing human T cells to interleukin-2.

Calcitriol↗
PubMedDate not supplied

Recent progress in atomic and chemical group effective potentials.

Recent progress on atomic and chemical group effective potentials is presented. The reviewed effective potentials follow a shape-consistent extraction technique from ab initio data, within a scalar relativistic approximation. Two types of averaged relativistic effective core potentials are considered: the correlated ones where a part of the correlation energy is included in the effective potential, and the polarized ones for which only the core polarization effects are taken into account. In addition spin-orbit polarized pseudopotentials have been extracted, and the effects of the core polarization are tested on the atomic spectroscopy of iodine. Finally a very recent chemical group effective methodology is presented, reducing the number of both electrons and nuclei explicitly treated. Chemical transferability is investigated, and test calculations on a cyclopentadienyl effective group potential are presented.

Journal Article↗