Monoclonal antibody against sialylated Lewis(a) antigen

We isolated hybridoma cells, which secreted monoclonal antibody (MAb) 121 SLE, an IgM showing the following reactivities: (1) by immunodiffusion, MAb 121 SLE and MAb NS 19-9 (a monoclonal antibody directed against a sialylated Lewis(a) antigen called CA 19-9) showed an identical precipitin line with mucin preparation containing this CA 19-9; (2) by immunoradiometric assay, MAb 121 SLE totally inhibited fixation of radiolabelled MAb NS 19-9; (3) by immunoperoxidase, MAb 121 SLE stained the normal gastrointestinal mucosa of Le-positive individuals exclusively, and this staining disappeared after neuraminidase treatment, as observed using MAb NS 19-9. However, the pattern of the staining obtained with MAb 121 SLE differed slightly from that given by MAb 19-9 on the different positive areas of the gastrointestinal mucosae. These differences principally concerned the number of positive epithelial cells and the intensity of their staining; (4) moreover, antibodies against idiotype determinant of NS 19-9 antibody did not react with the antibody 121 SLE. We concluded that MAb 121 SLE is different from the MAb NS 19-9. However, both these antibodies were associated with the same molecular sialylated Lewis(a) structure.     

Specificity of different organic nitrates to elicit NO formation in rabbit vascular tissues and organs in vivo.

1. In the present study we assessed the formation of nitric oxide (NO) from classical and thiol-containing organic nitrates in vascular tissues and organs of anaesthetized rabbits, and established a relationship between the relaxant response elicited by nitroglycerin (NTG) and NO formation in the rabbit isolated aorta. Furthermore, the effect of isolated cytochrome P450 on NO formation from organic nitrates was investigated. 2. Rabbits received diethyldithiocarbamate (DETC; 200 mg kg-1 initial bolus i.p. and 200 mg kg-1 during 20 min, i.v.) and either saline, or one of the following organic nitrates: nitroglycerin (NTG, 0.5 mg kg-1), isosorbide dinitrate (ISDN), N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 3672), S-carboxyethyl-N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 5185), at 10 mg kg-1 each. After 20 min the animals were killed, blood vessels and organs were removed, and subsequently analyzed for spin-trapped NO by cryogenic electron spin resonance (e.s.r.) spectroscopy. 3. In the saline-treated control group, NO remained below the detection limit in all vessels and organs. In contrast, all of the nitrates tested elicited measurable NO formation, which was higher in organs (liver, kidney, heart, lung, spleen) (up to 4.8 nmol g-1 20 min-1) than in blood vessels (vena cava, mesenteric bed, femoral artery, aorta) (up to 0.7 nmol g-1 20 min-1). Classical organic nitrates (NTG, ISDN) formed NO preferentially in the mesenteric bed and the vena cava, while the SPM compounds elicited comparable NO formation in veins and arteries. 4. Using a similar spin trapping technique, NO formation was assessed in vitro in phenylephrine-precontracted rabbit aortic rings. The maximal relaxation elicited by a first exposure (10 min) to NTG (0.3 to 10 microM) was positively correlated (r = 0.8) with the net increase (NTG minus basal) of NO spin-trapped during a second exposure to the same concentration of NTG in the presence of DETC. 5. Cytochrome P450 purified from rabbit liver enhanced NO formation in a NADPH-dependent fashion from NTG, but not from the other nitrates, as assessed by activation of purified soluble guanylyl cyclase. 6. We conclude that the vessel selective action of different organic nitrates in vivo reflects differences in vascular NO formation. Thus, efficient preload reduction by classical organic nitrates can be accounted for by higher NO formation in venous capacitance as compared to arterial conductance and resistance vessels. In contrast, NO is released from cysteine-containing nitrates (SPMs) to a similar extent in arteries and veins, presumably independently of an organic nitrate-specific biotransformation. Limited tissue bioavailability of NTG and ISDN might account for low NO formation in the aorta, while true differences in biotransformation seem to account for differences in NO formation in the other vascular tissues.     

Importance of the ratio between ionized and total Mg in serum or plasma: new data on the regulation of Mg status and practical importance of total Mg concentration in the investigation of Mg imbalance.

There is an inverse relationship between Mg balance and the ratio ionized Mg/total Mg in serum or plasma: in Mg excess, the ratio is decreased and in Mg deficiency the ratio is increased. It works as if a subtle homeostasic compensatory reaction modified the proportion of the most biologically active fraction of blood Mg in order to reduce the effects of Mg imbalance. Easy, available and unexpensive, the evaluation of total Mg in plasma or serum appears as a better marker than ionized Mg in Mg imbalance: it should be priviledged as the initial investigation in clinical practice.     

Importance of magnesium depletion with hypofunction of the biological clock in the pathophysiology of headhaches with photophobia, sudden infant death and some clinical forms of multiple sclerosis.

Mg depletion is a type of Mg deficit due to a dysregulation of the Mg status. It cannot be corrected through nutritional supplementation only, but requires the most specific correction of the dysregulating mechanism. Among those, Biological Clock (BC) dysrhythmias are to be considered. The aim of this study is to analyze the clinical forms of Mg depletion with hypofunction of the Biological Clock (hBC). hBC may be due to either Primary disorders of BC [Suprachiasmatic Nuclei (SCN) and pineal gland (PG)] or Secondary with homeostatic response [reactive Photophobia (Pphi] to light neurostimulating effects [Nervous Hyper Excitability (NHE)]. The symptomatology is mainly diurnal and observed during fair weather (Spring,Summer). The elective marker of hBC is represented by a decrease in melatonin and in its metabolites in various fluids. The clinical forms of NHE due to Mg depletion with hBC are central and peripheral. The central forms associate anxiety, headaches and dyssomnia. The peripheral manifestations are neuromuscular: photosensitive epilepsia mainly. Three chronopathological forms of Mg depletion with hBC have been highlighted: 1. Headaches with Pphi: mainly migraine; 2. Sudden Infant Death Syndrome (SIDS); 3. Multiple Sclerosis (MS).- Headaches with Pphi, migraine particularly. These cephalalgias are diurnal with Pphi and are aggravated during the fair seasons (particularly during midnight sun-summer). Migraine is their typical form with its dishabituation to visual stimuli and its occipital cortex hyperexcitability. Comorbidity with anxiety is frequent. In 2/3 of the cases, it appears first.- SIDS might be linked to an impaired maturation of both photoendocrine system and brown adipose tissue. MS may be associated with primary disorders of BC Clinical forms of Mg depletion with hBC in MS present diurnal exacerbations and relapses during fair seasons. They have been underestimated because they disagree with the dogma of the < latitude gradient >, presently questioned. Comorbidities with anxiety and migraine are frequent.hBC may be treated by using darkness therapy with a balanced Mg status. Absolute light deprivation should only be used only in acute indications and is time-limited. Partial substitutive therapy and chromatotherapy have not been validated yet and are still uncertain.     

Aneuploidy and expression of gastric-associated mucus antigens M1 and CEA in colorectal adenomas

A series of 55 flow cytometric characterized colorectal adenomas was analyzed with four different monoclonal antibodies (Mabs) for the occurrence of M1 antigens (associated with gastric fucomucins) and one Mab for carcinoembryonic antigen (CEA). The antigens were detected with an indirect immunoperoxidase technic on paraffin sections after pretreatment with pronase for M1 antigens and without pretreatment for CEA. The staining pattern revealed different correlations with the various parameters, i.e., size, histologic type, atypia, and ploidy of the adenomas. Especially the cytoplasmic staining of anti-M1, Mab (1-13 M1) correlated well with aneuploidy (R = 0.43; P less than or equal to 0.001) and with the DNA index (R = 0.34; P less than or equal to 0.01). Staining of the anti-CEA Mab only correlated with the size of the adenomas (R = 0.29; P less than or equal to 0.03). It is concluded that the immunoreactivity of Mab (1-13 M1), which significantly correlated with aneuploidy, may be associated with malignant transformation in the adenoma-carcinoma sequence.     

New heparin-like insoluble materials: Part II

Heparin-like insoluble materials were prepared by reacting different α-amino acids with cross-linked chlorosulfonated polystyrene. The amount of thrombin inactivated by these resins, when suspended in plasma, is linearly dependent upon the polymer content for all the materials studied and upon the thrombin concentrations examined. The anticoagulant potency of each resin can be expressed as the activity of the sulfonate groups added to the activity of the α-amino acid sulfamide groups linked to polystyrene. The activity coefficients of substituting groups increase according to the following sequence: (1) −SO₂ But NH₂; (2) −SO ₃ ⁻ , −SO₂ Ala, −SO₂ Phe; (3) −SO₂ Met, −SO₂ OH Pro, −SO₂ Pro, −SO₂ Thr, −SO₂ Z Lys; (4) −SO₂ Glu.     

The epithelial-mesenchymal transition induces aggressivity of mucinous cystic neoplasm of the pancreas with neuroendocrine component: An immunohistochemistry study

Background

Pancreatic mucinous cystic neoplasms (MCN) are rare tumors that are usually diagnosed in females.

Effect of maternal cadmium exposure on postnatal development and tissue cadmium,copper and zinc concentrations in rats

Administration of 60 ppm cadmium (Cd) in drinking water from the 1^st to the 20^th day of gestation to female rats did not affect the viability, body weight gain, food, and water consumption of offspring. The blood hemoglobin level was reduced in 2-week-old females and males but not in 16-week-old offspring. Hematocrit and serum glucose level were not affected at either age. Cadmium concentration in the intestinal wall was increased in both age groups, with marginal uptake in other organs. A decrease in copper (Cu) concentration was found in the brain of 2-week-old offspring of both sexes and of 16-week-old females. The brain zinc (Zn) concentration was decreased only in 16-week-old animals. The physical and neuromuscular development of offspring before weaning was not impaired by maternal Cd treatment. The alterations in Cu and Zn metabolism were associated with reduced locomotor activity and affected open-field behavior in adult offspring of either sex and with decreased avoidance acquisition in adult female offspring.The results obtained suggest a relationship between the reduced brain Cu and Zn levels and CNS dysfunction in adult offspring of female rats exposed to Cd during gestation.     

The catalytic rate constant. Effect of acetone on acidic hydrolysis of ester cyclohexyl acidacetylomethyl (AmMC)

The catalytic rate constants k(HCl) were established for hydrolysis of beta-lactam moiety in AmMC using equation k(obs) = k(H2O) + k(HCl)[HCl]. The estimate the effect of aceton the relation log k(HCl) = log kD + k Z(mu)/D was applied. The rate constant increases with the decrease of dielectric constant of the solvent.