Taxol-induced reorganization of the microtubule system in murine splenic lymphocytes inhibits response to allogeneic cells but not to concanavalin A

The exposure of mouse splenic lymphocytes to the microtubule assembly-promoting drug taxol (10 microM for 4 h) results in an extensive reorganization of the microtubule system to form one to a few large bundles of microtubules, which extend from the centrosome. Lymphocytes pretreated with taxol for 4 h, or cultured in the continued presence of taxol, respond normally to the mitogen concanavalin A up to, and including, the stage of DNA replication. In contrast, the induction of DNA synthesis during the alloactivation of lymphocytes is inhibited when taxol is present in the mixed leukocyte culture. If the stimulators are pretreated with this drug, the mixed leukocyte reaction occurs normally, but pretreatment of the responders inhibits the proliferative response markedly. Microscopic observations of nuclear morphologies in these populations and autoradiography indicate that taxol inhibition occurs early in alloactivation, prior to DNA replication. The responding ability of taxol-treated lymphocytes is not restored to control levels by the addition of interleukin 2, leading to the suggestion that interleukin 2 receptors do not emerge or function normally in these cells. We conclude that the capacity to respond to allogeneic cells, but not to a mitogen, is dependent on the presence of the normal submembranous organization of the microtubule system.     

Tumour invasion: effects of cell adhesion and motility

Metastasis is the major cause of failure in cancer therapy. Recent studies of the molecular cell biology of the metastatic process have provided new insights into the mechanisms of cell-cell adhesion, cell-substrate adhesion and cell motility that underly invasion by tumour cells. In this review, Van Roy and Mareel discuss the role of proteins with invasion-promoting and invasion-suppressing functions in metastasis.     

Sex differences in the inhibition by ATD of testosterone-activated mounting behavior in guinea pigs

Adult male and female guinea pigs from a genetically heterogeneous stock were gonadectomized and tested for mounting behavior before and during various treatments with testosterone cypionate (TC) alone or in combination with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). ATD was implanted subdermally in Silastic capsules (either 1 or 2 in females; 2 or 3 in males). In females 2 capsules of ATD completely blocked the behavioral effects of TC, and 1 capsule was an effective blocker in 58% of the females. The blocking effect was reversed by injection of diethylstilbestrol. In males, there was no measurable effect of ATD on mounting activity even when 3 capsules were implanted. Moreover, the TC induction of higher components of male sexual behavior (intromission and ejaculation) was also not impaired by ATD. Results are interpreted as indicating that either the process of male sexual differentiation or the male genotype eliminates the requirement for aromatization in androgenic activation of sexual behavior.     

Heterokaryosis inPolyporus ostreiformis for improved yield of exo-1,4-α-d-glucosidase

An amylolytic strain ofPolyporus ostreiformis was subjected to multistep mutagenic treatment and a heterokaryotic mutant was finally selected which produced exo-1,4-α-d-glucosidase in a yield of 2.54 U/mL against the parental yield of 0.42 U/mL. The crude enzyme extract of the mutant was used to hydrolyze soluble starch, maltose and amylopectin and chromatography of the hydrolyzates revealed exo-1,4-α-D-glucosidase activity predominant in the enzyme system.     

Direct transesterification of all classes of lipids in a one-step reaction

Conventional techniques for the determination of fatty acid composition of lipids require solvent extraction, purification, hydrolysis, and derivatization procedures that are both lengthy and cumbersome. A 1-hr direct transesterification procedure carried out in methanol-benzene 4:1 with acetyl chloride circumvented all these steps and was applicable for analysis of both simple (triglycerides) and complex lipids (cholesteryl esters, phospholipids, and sphingomyelin). Recoveries (greater than 95%) of standards unaffected by the presence of 5% water and 200 mg of silica suggested that the technique could be used for the quantitative analysis of total fatty acids as well as of fatty acids in classes of lipids separated on silica from biological samples. When compared to the Folch procedure, the technique led to a 20.1% increase in total fatty acids for plasma, 3.9% for feces, 7.4% for bile, and 9.7% for rat liver. We therefore conclude that this one-step direct transesterification procedure is superior to currently used methods, not only because of its simplicity and speed, but also because of its added precision.     

Prevention of stress-induced gastric ulcers by dopamine agonists in the rat

Dopamine (DA) and DA agonists have been shown to exert a protective role against the formation of duodenal ulcers. The effect of stimulation of DA receptors on the development of stress-induced gastric ulcers is currently unknown. Accordingly, we evaluated the effect of several DA agonists on the development of gastric ulcers induced by 3 h of cold + restraint stress (CRS) in rats. Apomorphine, d-amphetamine, methylphenidate, and threo-dl-p-hydroxymethylphenidate (an hydroxylated analog of methylphenidate), significantly reduced both the incidence and severity of CRS-induced gastric ulcers. The gastric cytoprotection afforded by these agents was dose-related, and completely antagonized by pretreatment with the peripheally acting DA antagonist domperidone. Because domperidone blocks peripheral, but not central, DA receptors, and since the entry of threo-dl-p-hydroxymethylphenidate across the blood-brain barrier into the brain is restricted to a great extent, we conclude that stimulation of peripheral DA receptors is primarily involved in the gastric cytoprotection induced by dopamimetics.The pathogenesis of stress-induced gastric ulcers remains largely unknown, and significant efforts have been made over the last decade to functionally characterize some of the factors involved in the etiology of this disease. Considerable attention has been focused on gastric acid secretion, but its primary role in stress-induced gastric ulcer disease remains uncertain. In fact, agents which effectively inhibit or neutralize gastric acid secretion such as cimetidine or antacids do not necessarily exert protection against stress-induced gastric ulcers (1,2). Moreover, in our original studies with neurotensin, a brain and gastrointestinal peptide, we have found that central administration of this neuropeptide, which completely prevents the development of cold + restraint stress (CRS)-induced gastric ulcers, does not appreciably alter gastric acid secretion (2). These findings support the contention that gastric acid secretion may not be an important factor in the development of this type of gastric ulcer.There is, however, considerable evidence that the automatic nervous system plays an intermediary role in the development of these ulcers (3,4). In this regard, surgical or pharmacological blockade of the vagal (cholinergic) division of the autonomic nervous system prevents the appearance of stress-associated gastric ulcers (5,6). Direct stimulation of catecholamine receptors, or indirect activation via increased sympathetic outflow to the periphery (7,4,8–11) appears to produce a salutary effect of stress-induced gastric ulcers.Szabo and his associates (12, 13, 14) have extensively studied the anti ulcer effects of dopamine (DA) in duodenal ulcer formation. Whether DA also modifies the development of stress-induced gastric ulcers is currently unknown.We have therefore evaluated the effect of selected DA receptor agonists and antagonists on CRS-induced gastric ulcer formation in rats.     

Haemolysis of rabbit erythrocytes by a lectin from the seeds of<Emphasis Type="Italic">Croton tiglium</Emphasis>

The kinetics of haemolysis of rabbit erythrocytes byCroton tiglium lectin was studied as a function of concentration of the lectin and erythrocytes. The length of the prelytic period decreased with increasing lectin concentrations, indicating that the secondary events at the membrane which follow the binding of the lectin to cell surface carbohydrate receptors are accelerated at higher surface concentrations of the lectin. The rate or extent of haemolysis was not affected by the inclusion of ions like K⁺, Ca²⁺ and Mg²⁺ in the medium or by the substitution of ionic medium by a non-ionic medium. The inhibition of haemagglutination and haemolysis of rabbit red cells byCroton tiglium lectin by antilectin rabbit serum was observed. A possible mechanism of haemolysis by the lectin is discussed.     

Plant lectins specific for N-acetyl-β-D-galactosamine

N-Acetyl-D-galactosamine in β-linkage being ubiquitous in cell surface glycoproteins, their interaction with lectins specific for this sugar moiety may be a significant event in cell adhesion phenomena. This article discusses the common β-N-acetyl galactosamine-specific lectins, with particular stress on the lectin from winged beans (Psophocarpus tetragonolobus).