Interactions in the complement-mediated lysis of blood group AB erythrocytes sensitized simultaneously with anti-A and anti-B monoclonal antibodies

The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a 51Cr-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of C1q and C3 bound to sensitized red cells was measured by using purified, 125I-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and C1q binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more C1q than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of C1q to an antibody-sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization.     

Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood

The development of a hypoglycemic alarm system using a subcutaneous glucose sensor implies that a decrease in blood glucose is rapidly followed by a decrease in the signal generated by the sensor. In a first set of experiments the linearity and the kinetics of the response of sensors implanted in the subcutaneous tissue of normal rats were investigated during a progressive increase in plasma glucose concentration: the sensitivities determined between 5 and 10 mM and between 10 and 15 mM were not significantly different, and a 5-10 min delay in the sensor's response was observed. In a second set of experiments, performed in diabetic rats, the kinetics of the decrease in subcutaneous glucose concentration following insulin administration was monitored during a decrease in plasma glucose level, from 15 to 3 mmol/L. During the 20 first min following insulin administration, the sensor monitored glucose concentration in subcutaneous tissue with no lag time. Subsequently, the decrease in the estimation of subcutaneous glucose concentration preceded that of plasma glucose. This phenomenon was not observed when the same sensors were investigated in vitro during a similar decrease in glucose concentration and may be due to a mechanism occurring in vivo, such as the effect of insulin on glucose transfer from the interstitial space to the cells surrounding the sensor. It reinforces the interest of the use of implantable glucose sensors as a part of a hypoglycemic alarm.     

PROBABILISTIC MODELLING OF LIGNIN LIQUEFACTION

The results of the thermal and catalytic reactions of lignin model compounds are used in the a priori prediction of its liquefaction. Lignin was defined probabilistically as an ensemble of single ring aromatics with substituents on each of their six ring positions. Elements in a substituent vector x¹, for each ring position i, were matched into all possible combinations to describe lignin. Initial number fractions, or probabilities, for each vector element were ascertained through inspection of lignin structural data. The reaction of lignins altered the probabilities within each substituent vector, and reaction products were also calculated by matching all combinations of vector elements for each ring position. Model compound results provided the identities and rates of change of vector elements.

This simulation of lignin liquefaction predicted the yields of permanent gases, aqueous liquids, single- and two-ring phenolic products, and a carbonaceous residue. The impact of the distribution of oligomeric sizes on catalyst effectiveness was probed.     

Die Anfänge der neuzeitlichen Chemie in der Pharmazie und Metallurgie. Zu E.F. Geoffroys tabelle stofflicher Beziehungen

E.F. Geoffroy's table of different relations (“rapports”) between different chemical substances is mainly based on empirical knowledge accumulated in 16th and 17th century metallurgy and pharmacy. The substances listed in the left half of the table were basic for the formation of salts which were produced for medical ends in the chemical-pharmaceutical practice of the 17th century. The right half of the table refers to substances and operations of metallurgy which had already been described in the metallurgical writings of the 16th century. Even Geoffroy's ordering of the substances within the columns of his table has its origin in metallurgical and pharmaceutical practice. The key concept of the conceptual framework underlying the table and its commentary is the concept of chemical compound which emerged at the end of the 17th century. Geoffroy extends the range of application of this concept, which was first limited to chemical artefacts, to include natural bodies. Eliminating the peripatetical distinction between natural bodies and chemical artefacts he formulates a new research program, consisting in the determination of the “laws” of the relations (“rapports”) between different chemical substances.     

Effect of maturation on alpha-adrenoceptor activity in newborn piglet mesentery

To characterize the mesenteric alpha1- and alpha2-adrenoceptor populations in newborn piglets, an extracorporeal circuit was established to control intestinal blood flow in 0- to 2-day old and 10- to 14-day old animals. In both groups, alpha-adrenoceptor activation was first documented by observing dose-dependent increases in mesenteric perfusion pressure after intramesenteric arterial injection of alpha-adrenoceptor agonists. In the 10- to 14-day old piglets, mesenteric vasoconstrictor responses to alpha1-adrenoceptor agonists (methoxamine and norepinephrine) and an alpha2-adrenoceptor agonist (BHT-933) were each blunted (P < 0.05, analysis of variance) by peripheral intravenous injections of prazosin (an alpha1-adrenoceptor antagonist) and yohimbine (an alpha2-adrenoceptor antagonist), respectively. The mesenteric vasoconstrictor responses to those agonists were not significantly attenuated by prazosin or yohimbine in 0- to 2-day old animals, nor were they blunted by YM-12617 (alpha1-adrenoceptor antagonist) or idazoxan (alpha2-adrenoceptor antagonist)--compounds that are structurally unrelated to prazosin and yohimbine, respectively. In addition, mesenteric vasoconstrictor responses to other known vasoconstrictor agents--angiotensin II, neuropeptide Y, and a thromboxane A2 mimic (U-46619)--were not effected in either age group by prazosin or yohimbine, implying these agents act independently of alpha-adrenoceptor mechanisms. These data suggest that (1) there exists functional mesenteric alpha1- and alpha2-adrenoceptor-like activity in 10- to 14-day old piglets that, in 0- to 2-day old animals, is not specifically expressed; and (2) mesenteric alpha-adrenoceptor function becomes more selective as newborn piglets mature.     

Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts

We studied 722 reexcision scars of benign and malignant lesions (except melanocytic lesions) excised over a 24-month period. The formalin-fixed, paraffin-embedded tissue sections were examined histologically and immunohistochemically. The histological features of melanocytic hyperplasia were present in 59 cases (8%), 56 from the sun-exposed skin of the face and neck and three from the trunk [p < 0.00001]. The most common sites were the nose and lower eyelids, but the forehead was also frequently involved. Of the 59 patients, 41 were women (p < 0.0001). Basal cell carcinoma was the most frequent original lesion in both sexes (80%). No melanocytic hyperplasia was found in 663 cases (298 on the trunk and extremities and 365 on the head and neck). We have seen this reaction pattern following reexcision of melanocytic lesions as well. Thus, interpreting reexcision margins when lentigo maligna or similar lesions are reexcised may be fraught with difficulty. It is important for pathologists and dermatopathologists to recognize this phenomenon because histologically the presence of increased numbers of large melanocytes could be misinterpreted as melanoma in situ.