Sodium-hydrogen exchange in erythrocytes of patients with acute deep venous thromboses.

The rate of delta microH(+)-induced Na/H-exchange in erythrocytes of patients with occlusive and with floating types of acute deep venous thromboses, and in control volunteers, was estimated. In patients with occlusive thrombi Na/H-exchange was revealed to be fourfold higher in comparison with patients with floating thrombi and with controls, while no difference was observed between the two latter groups.     

Die lokale Leukozytenreaktion bei der intraperitonealen Infektion der Maus mitE. coli

Summary Intraperitoneal aggregation of leucocytes is produced in an identical manner by intraperitoneal application of different amounts of living and dead bacteria and bacterial products. The maximum accumulation occurs with medium dosages of bacteria or their products, with high dosages no leucocytic accumulation is produced. Pretreatment with selected LPS of bacteria enhances the intraperitoneal accumulation of leucocytes also with the high amounts of bacteria, whereas the reaction in not pretreated with LPS is suppressed. Parallel to the increase of the intraperitoneal leucocytic accumulation the animals are protected against the infection with high amounts of bacteria, to which they succumb if not pretreated with LPS.     

Evidence for possible emergence of immunochemically distinct nucleotide-peptides in malignant transformation.

Antibodies against nucleotide-peptides of beef heart do crossreact with nucleotide-peptides of other beef organs, but with nucleotide-peptides of Ehrlich tumor cells. Antibodies against the latter do not crossreact with nucleotide-peptides of normal organs, but do so with nucleotide-peptides of a rat hepatoma.     

Preservation of hematopoietic stem cells by slow freezing and elimination of the heat of fusion]

Previous experiments, in dogs with fresh bone marrow or bone marrow frozen with a modified freezing system have demonstrated a 100% recovery of frozen stem cells, stored for periods up to 5 months. Five patients, three with drug resistant acute leukemia and two with metastic carcinomas, have been treated with a high dose combination chemotherapy regimen (TACC) followed by reinfusion of marrow cryopreserved with the same modified freezing system. Following the reinfusion of marrow, autologous engraftment was demonstrated on bone marrow aspiration between days 5 and 10.     

Albrecht von Haller on academies and the advancement of science: the case of Göttingen

This article approaches eighteenth-century views on scientific academies by examining Haller's utterances, public and private, especially those occasioned by the founding of the Göttingen Society. It deals in turn with his understanding of the distinctive purpose of academies, with his explanation of the chief ways in which they realized this end, with his thoughts on their broader usefulness, and finally with his various reasons for considering close ties with the state to be essential to their productive and harmonious operations.     

Adaptive prediction for stochastic processes with markov jump parameters

This paper is concerned with the adaptive prediction for stochastic processes with abruptly changing parameters modelled as a finite-state Markov chain. The Markov transition matrix is assumed to be known. For the coloured noise disturbance case, it is shown that the optimal prediction algorithm requires a bank of elemental predictors running in parallel with its number growing exponentially with time. If the noise disturbance is white, it is found that the number of the elemental predictors required increases exponentially with the prediction ahead step instead of time. A suboptimal predictor is proposed with substantial reduced storage and computational requirements. Simulation examples show the good performance of the proposed algorithms.     

Effect of in vivo pre-treatment with oestradiol and either GnRH, GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro

In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting effect of oestradiol became smaller with increasing rates of in vivo administration of GnRH or AG, but not with ANT. With respect to both depletion of the LH stores and suppression of the augmenting effect of oestradiol, AG ist about 20 times as potent as GnRH.     

Proinsulin C-peptide and its C-terminal pentapeptide: degradation in human serum and Schiff base formation with subsequent CO<Subscript>2</Subscript> incorporation

Processing of human proinsulin C-peptide and its C-terminal pentapeptide in blood serum was studied using reverse-phase HPLC and electrospray mass spectrometry. The results reveal degradation of both peptides, with a longer half-life for intact C-peptide than for the C-terminal pentapeptide. Products from C-peptide degradation were not distinguishable from the peptide background, suggesting endopeptidase degradation of C-peptide. In contrast, a set of products from the C-terminal pentapeptide were identifiable and corresponded to successive losses from the N terminus, showing that the pentapeptide is degraded by aminopeptidase in serum. Consistent with this finding, a slower degradation was found for the N-acetyl-protected pentapeptide. Removal of serum proteins by acetone precipitation produced N-terminally carbamate-modified C-peptide via a Schiff base intermediate (a ketimine with acetone), to which CO(2) was added and acetone removed, generating a cyclic side chain via anhydride formation. The modification was not seen with the pyroglutamate form of C-peptide, with the N-terminally acetylated C-peptide, or with a control peptide having N-terminal Phe, but was found with human C-peptide, its N-terminal tetrapeptide, and a rat C-peptide fragment (all with N-terminal Glu). Hence, the modification appears to require N-terminal Glu, but this is not the only prerequisite since the C-terminal pentapeptide and another control peptide (also starting with Glu) were not modified. A peptide aldimine Schiff base leading to CO(2) incorporation was detected with formaldehyde in NaHCO(3). The observation that C-peptide forms Schiff bases with ketones/aldehydes, enhancing covalent attachment of CO(2), may have biological implications.     

Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

Effect of in vivo pre-treatment with oestradiol and either GnRH,GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro

Summary In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting effect of oestradiol became smaller with increasing rates of in vivo administration of GnRH or AG, but not with ANT. With respect to both depletion of the LH stores and suppression of the augmenting effect of oestradiol, AG ist about 20 times as potent as GnRH.     

Immunological demonstration of large quantities of glycogen or of a glycogen-like substance in human embryonic colon cells and in colon carcinomas by means of rabbit antisera raised against a strain of Escherichia coli 013]

Rabbit antisera raised against a strain of E. coli 013, with a strong antiglycogen activity, were tested on human fetal and normal adult colons, on colon carcinomas, and on colon tumor cells in culture (HT29). Only very rare granules were present in adult normal colons when tested with the immunofluorescence method. In faetal colons, in 12 out of 14 carcinomas, and on HT29 cells, the immunofluorescent reactions were similar to those observed in normal liver. The reactions were negative after previous treatment with alpha-amylase. They were inhibited with glycogen, with phenol-alcohol, perchloric, and trichloroacetic extracts from faetal colons, and with a tumor trichloroacetic extract. The extracts precipitated with anti-E. coli 013 antisera. They had a strong inhibiting activity in a radioimmunoassay test with labeled glycogen. The extracts from normal adult colons did not precipitate with the antisera and they had no inhibiting activity in either immunofluorescence and radioimmunoassay tests.     

Supervenience and (non-modal) reductionism in Leibniz’s philosophy of time

It has recently been suggested that, for Leibniz, temporal facts globally supervene on causal facts, with the result that worlds differing with respect to their causal facts can be indiscernible with respect to their temporal facts. Such an interpretation is at variance with more traditional readings of Leibniz’s causal theory of time, which hold that Leibniz reduces temporal facts to causal facts. In this article, I argue against the global supervenience construal of Leibniz’s philosophy of time. On the view of Leibniz defended here, he adopts a non-modal reduction of time to events, a form of reductionism that entails a strong covariation between a world’s temporal facts and its causal facts. Consequently, worlds discernible with respect to their temporal facts must be discernible with respect to their causal facts, and worlds discernible with respect to their causal facts must be discernible with respect to their temporal facts. This position strongly favors the standard identificatory reduction of time to causation often imputed to Leibniz.     

有无植物条件下明渠水流紊动特性对比

在可变坡水槽中，模拟了带枝杈植物对明渠水流的干扰作用，借助超声多普勒流速仪（ADV）测量了不同水深下垂线不同测点的瞬时流速，计算了各测点的三维时均流速、脉动强度及雷诺应力等紊动参数，通过与无植物干扰的明渠均匀流紊动特性进行对比，分析植物对水流紊动参数的影响规律。试验结果表明：在有植物明渠水流中，时均流速呈三区分布特征；脉动强度及雷诺应力均在植物顶部附近出现最大值；脉动强度明显增大，在3个方向上趋于接近；可以用植物顶部以上的雷诺应力分布推求摩阻流速。     

Evolution of anti-Rh antibodies idiotypy in a blood donor over 9 years]

Anti-idiotypic sera were obtained in Rabbits immunized with Rh antibodies (isolated from the serum sample collected in 1974 from a Blood Donor). The sera agglutinate, at high titers, red cells coated with the immunizing antibodies and, at different titers, cells coated with antibodies from serum samples taken at other periods. Inhibition of hemagglutination of anti-idiotypic sera by different samples from the same Donor was complete with the immunizing serum and partial with other samples. These results show that idiotypes or idiotypic specificities appeared or disappeared during the period studied and represent the first observation on evolution of antibody idiotypy in Man.     

TSH-receptor antibodies, HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism.

The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.     

TSH-Receptor antibodies,HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism

Summary The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.     

Su un criterio di valutazione dell'attività di un farmaco antitubercolare nella cavia infettata con carica massiva

Summary It is reported that the data of index of tuberculous process obtained after 70 days of massive infection (with 1 mg bacilli) and immediately treated with antitubercular drug, are similar to the data observed in the guinea pig infected with a low dosage of bacilli and not treated with any antitubercular drug. The authors therefore suggest the use of this comparision for a test of the antitubercular activity of a drug.     

Einfluß antianaphylaktisch wirkender Stoffe auf die Antikörperproduktion

Summary To produce antisera of high antibody concentration animals after sensitization with protein have been reinjected with lethal doses of the antigen, protected against the shock-effect by substances with antihistamin properties (as example Antistin). The antibody concentration was considerably higher in these animals as in the other non-protected group reinjected with the highest tolerated antigen dosage.     

The effect of ligand on the kinetics of the sulfhydryl groups of human hemoglobin with p-mercuribenzoate

The rate of reaction of PMB with the masked sulfhydryls of human hemoglobin derivatives correlates well with the extent of dissociation for various ligands. It is suggested that the alpha1beta2 dimer of hemoglobin participates in the slow step of the reaction with PMB.     

Monoclonal antibodies against antigens on breast cancer cells

Summary Of 360 mAb obtained in a cell fusion experiment with the spleen cells of a mouse immunized with a mixture of different human breast carcinoma cells lines, 30 mAb were selected which reacted more strongly with tumor cells than with (noncancerous) fibroblasts. Theses mAb were tested for reactivity with additional types of cancerous and noncancerous tissues. Two mAb showed high tumor selectivity, but the corresponding epitopes on individual tumor cells were heterogeneously expressed. The mAb will be evaluated for in vivo applications.