Sesaminol from sesame seed induces apoptosis in human lymphoid leukemia Molt 4B cells

The exposure of human lymphoid leukemia Molt 4B cells to sesaminol, a component of sesame oil led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with sesaminol. The fragmentation of DNA by sesaminol to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These findings suggest that growth inhibition of Molt 4B cells by sesaminol results from the induction of apoptosis in the cells.     

Sequential changes of [H]forskolin, [H]cyclohexyladenosine and [H]PN200-110 binding sites in the brain of 6-hydroxydopamine-lesioned rats

Receptor autoradiographic technique was studied to investigate sequential changes in adenylyl cyclase, adenosine A1 receptors and L-type calcium channels in the striatum and substantia nigra 1-8 weeks after unilateral 6-hydroxydopamine injection of the medial forebrain bundle in rats. [3H]Forskolin, [3H]cyclohexyladenosine (CHA) and [3H]PN200-110 were used to label adenylyl cyclase, adenosine A1 receptors and L-type calcium channels, respectively. The degeneration of the nigrostriatal pathway caused a significant increase in [3H]forskolin binding in the striatum of both the ipsilateral and contralateral sides from 2 to 4 weeks post-lesion. The ipsilateral substantia nigra showed a transient increase in [3H]forskolin binding 4 weeks post-lesion. In contrast, [3H]CHA binding showed no significant change in most brain areas after lesioning. On the other hand, a conspicuous decrease in [3H]PN200-110 binding was observed in the dorsolateral striatum of ipsilateral side 4 weeks post-lesion. Thereafter, the striatum of both the ipsilateral and contralateral sides showed a significant decrease in [3H]PN200-110 binding 8 weeks post-lesion. These results demonstrate that unilateral 6-hydroxydopamine into the medial forebrain bundle of rats can experimentally cause a significant increase in adenylyl cyclase binding sites in the striatum and substantia nigra, whereas no conspicuous change in adenosine A1 receptors is observed in these areas during post-lesion. In contrast, L-type calcium channels were progressively damaged in the striatum after unilateral 6-hydroxydopamine treatment. These findings suggest that adenylyl cyclase and calcium system may contribute to the degeneration processes of the dopaminergic neurones.     

Serum leptin correlates with serum uric acid but not serum testosterone in non-obese male adolescents

To identify the serum factors that affect circulating leptin levels, we measured the serum concentrations of leptin, testosterone (T), estradiol (E), serum alanine aminotransferase, total cholesterol and uric acid (UA) in healthy male adolescents (age, 18.3 +/- 0.1 years, n=96). We also measured body mass index (BMI), percent body fat and thickness of skin fold to assess the effect of body constitution on serum leptin level. Since serum concentration of leptin significantly correlated with BMI (r=0.820, p<0.001), we analyzed the relation-ship between leptin/BMI ratio (L/BMI) and serum parameters. Analysis of data of subjects with normal serum T level showed a significant inverse correlation between L/BMI and serum T levels (n=96, r=-0.294, p<0.005), but no such correlation was present among non-obese subjects (n=70) with BMI of +/-20% of normal (22 kg/m2). There was no correlation between L/BMI and serum E level. Serum UA level significantly correlated with L/BMI in both the test group (n=96, r=0.520, p<0.001) and non-obese subjects (r=0.369, p<0.005). Stepwise multiple regression analysis showed that UA independently and significantly influenced serum leptin levels in both the test and control groups. Our results demonstrate that T weakly influences serum leptin concentration, and that UA concentrations strongly influences serum leptin in healthy male adolescents independent of their obesity level.     

Endothelin synthesis and receptors in human endometrium throughout the normal menstrual cycle

This study was undertaken to investigate the presence of messengerRNA (mRNA) for prepro-endothelin-I (ET-1) and the known receptorsubtypes (ETA and ETB) in human endometrium at different stagesof the menstrual cycle obtained at hysterectomy. Northern blotanalysis revealed expression of ET-1 mRNA in human endometriumduring the normal menstrual cycle. The concentration of ET-1mRNA in endometrial tissue was greater during the menstrualand proliferative phases than during the ovulatory and secretoryphases. Immunoreactive ET-1 was secreted into the medium ofisolated endometrial stromal cells. Oestradiol and progesteronesignificantly attenuated ET-1 release in endometrial stromalcells cultured for 6 days. ETA and ETB mRNA were also presentin endometrial tissue of the normal cycle. The concentrationof ETA receptor mRNA was greater in the proliferative phasethan in the secretory phase, whereas expression of ETB mRNAincreased in menstrual phase. ET-1 significantly increased extracellularaccumulation of cyclic AMP (cAMP), intracellular generationof inositol phosphates and significantly enhanced DNA synthesisin cultured endometrial stromal cells from the proliferativephase. Our results showed that human endometrial cells synthesizedand released ET-1, and contained ETA and ETB receptors whichwere functionally coupled to phosphoinositide breakdown andto adenylate cyclase with the increase of cAMP by ET-1 stimulation.Our findings suggest that ET-1 may have a potential autocrineand/or paracrine function in human endometrial stromal cells.     

Induction and separation of mouse helper T cells by lectins.

The capability of Lens culinaris agglutinin (LcA) to induce selectively the helper T cell activity affecting primary antibody response was demonstrated. In the presence of mouse spleen cells, activated with LcA at a concentration of 12 . 5 microgram/ml, optimal augmentation of the humoral immune response to sheep erythrocytes (SRBC) was observed. It was also demonstrated that Limulus polyphemus agglutinin (LPA), which was shown to possess carbohydrate-binding specificity directed to sialic acid residues, preferentially agglutinated helper T cells. Conversely, peanut agglutinin (PNA), which binds preferentially to the sugar sequence beta-D-Gal-(1 leads to 3)-D-GalNAc, did not agglutinate the helper cells. Furthermore, the stimulatory effect of LPA-agglutinated cells on the antibody response was abolished by treatment of the cells with anti-Thy-1 . 2 and complement. These results suggested that the helper cells induced by LcA were T cells and that they have abundant sialic acid residues exposed on the cell surface.     

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis.

ICAM-1 plays an important role in inflammatory diseases. We analysed ICAM-1 expression on BAL fluid cells and measured soluble ICAM-1 (sICAM-1) concentrations in sera and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar macrophages, and significantly increased values of circulating and BAL fluid sICAM-1 in EAA patients compared with controls. Successive measurement showed prompt decrease of both sICAM-1 values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients, sICAM-1 values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-1 values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar-arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-1 expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-1 in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA.     

The origin of molecular disease: functional abnormalities and consequent clinical symptoms caused by single amino acid substitutions

The discovery of sickle cell hemoglobin in 1949 lead to the concept of "molecular disease". Since then, the total number of abnormal hemoglobins has been increasing, reaching 750 in April, 1998. Of these, 91% are variants with single amino acid substitutions. A "scratch" made in the protein moiety can cause alterations in physicochemical properties such as oxygen affinity, stability and autooxidation of 50% of all variants, further causing hematological or clinical disorders with significant frequencies. Generally, these alterations in properties and consequent hematological or clinical disorders are closely related to the mode and intramolecular location of the mutation. Conventional laboratory methods for mass screening of abnormal hemoglobins such as electrophoresis, isoelectric focusing and ion-exchange HPLC may overlook clinically important variants which possess amino acid substitutions without change in the charge. Oxygen affinity measurement may be a useful method to detect silent variants. Modern apparatuses can quickly and conveniently construct a continuous oxygen dissociation curve from one drop of whole blood. The dissociation curve becomes biphasic when the red cell contains abnormal hemoglobin with abnormal oxygen affinity. The continuous curve recording is advantageous because the proportion of the abnormal hemoglobin component can be estimated and the abnormal chain, either alpha or beta, can be predicted based on the inflection point of the biphasic curve.     

Granzyme B-positive primary gastric T-cell lymphoma: gastric T-cell lymphoma with the possibility of extrathymic T cell origin

A case of primary gastric T-cell lymphoma, which was positive for granzyme B, is reported. The patient was a 47-year-old Japanese female who complained of a dull upper abdominal pain. Radiographic and endoscopic examinations revealed an ulcerative infiltrative lesion in her stomach. Following the confirmation of a high-grade malignant lymphoma, a distal gastrectomy with regional lymph nodal dissection was performed. The histology of the gastric lesion revealed a malignant lymphoma of the diffuse pleomorphic type without lymph nodal involvement. Immunohistochemistry revealed that the tumor cells were positive for LCA, CD3, TIA-1 and granzyme B, but were negative for CD4, CD8, CD56, CD30, L-26, EMA, TCR alpha/beta and TCR gamma/delta. Because the tumor cells showed T cell nature with cytotoxic activity proved by TIA-1 and granzyme B, and without evidence of further maturation of T cell, a malignant lymphoma originating from extrathymic-derived T cells was suggested.