Mannose-6-phosphate stimulates proliferation of neuronal precursor cells

The mitogenic signal function of mannose-6-phosphate (Man-6-P)/insulin-like growth factor II (IGF-II) receptors was studied in neuronal precursor cells from developing rat brain (E15). About 30% of the cellular Man-6-P/IGF-II receptors were present on the cell surface. Man-6-P and IGF-II stimulated DNA synthesis twofold and their effects were additive. Antibody 3637 to the Man-6-P/IGF-II receptor blocked the response to Man-6-P but not that to IGF-II. Other phosphorylated hexoses were also active. Fructose-1-phosphate was equally potent with Man-6-P, whereas glucose-6-phosphate was 5 times less potent. We conclude that Man-6-P-containing proteins and IGF-II act as mitogens in developing brain by interaction with the Man-6-P/IGF-II receptor and the IGF-I receptor, respectively.     

The effect of two proteinase inhibitors, E-64 and the Bowman-Birk inhibitor, on the developmental time and mortality of Acanthoscelides obtectus

An artificial bean seed system was used to evaluate the effects of a cysteine proteinase inhibitor (E-64) and a serine proteinase inhibitor (Bowman-Birk inhibitor) on the developmental time and mortality of the common bean weevil, Acanthoscelides obtectus (Say). These inhibitors were incorporated into artificial bean seeds on which the insect fed. To better understand the mode of action of these inhibitors, free amino acids were also added to the seeds, alone and in combination with the inhibitors. E-64 was found to be highly effective in delaying development and increasing mortality of the insect. Both effects were directly related to the concentration of E-64. Bowman-Birk inhibitor had little effect on these parameters. Assays of gut proteolytic activity of insects reared on artificial seeds with various levels of E-64 demonstrated a direct relationship between E-64 concentration in the diet and reduction of gut proteolytic activity. Free amino acid supplementation to the diet did not prevent inhibition of gut proteolytic activity by E-64, but did reverse its effects on developmental time and mortality, strengthening the hypothesis that E-64 operates by inhibition of essential digestive proteinase activity.

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Résumé Des grains artificiels de haricot ont été utilisés pour évaluer les effets sur la durée de développement et la mortalité d' Acanthoscelides obtectus. Say d'inhibiteurs de la protéinase de la cystéine (E-64) et de la protéinase de la sérine (l'inhibiteur de Bowman-Birk). Ces inhibiteurs avaient été incorporés dans les grains artificiels. Pour mieux comprendre leur voie d'action, des acides aminés libres étaient ajoutés à ces graines, seuls ou combinés aux inhibiteurs. E-64 a très efficacement retardé le développement et accru la mortalité; ces 2 effets étaient liés à sa concentration. L'inhibiteur de Bowman-Birk a eu peu d'effets sur ces paramètres. Des expériences sur l'activité protéolytique du tube digestif d'insectes élevés sur des graines artificielles avec différentes concentrations de E-64 ont montré une relation directe entre la concentration en E-64 et la réduction de l'activité protéolytique. L'addition d'acides aminés libres dans l'aliment n'a pas empêché l'inhibition de l'activité protéolytique par E-64, mais a inversé ses effets sur la durée de développement et la mortalité, renforçant l'hypothèse que E-64 agit en inhibant l'activité protéinase digestive essentielle.

     

Protein HMG-17 is hyper-expressed in rat glucagonoma. Single-step isolation and sequencing

High-mobility-group protein 17 (HMG-17) was identified by reversed-phase high-performance liquid chromatography analysis as a major component in acidic extracts of transplantable rat glucagonoma tissue but not in insulinoma tissue of similar origin. The peptide was purified in a single step and the entire sequence of 89 amino acids was determined. Rat HMG-17 has a molecular mass of 9238 Da and shows strong similarity to human, bovine (94.4%) and chicken (88.8%) HMG-17. Six of the seven residues which vary among the mammalian sequences are located within a short segment (positions 64-83) present in the acidic, non-DNA-binding C-terminal part of HMG-17. This region shows least similarity to the otherwise related proteins HMG-14 and H6 (a trout HMG protein). Interestingly, four of the six variable positions are Asp in rat HMG-17 which results in an overall net increase in the negative charge of the C-terminal region. The nature of selective hyper-expression of HMG-17 in glucagon but not in insulin-producing tumor tissue remains to be clarified.     

A quantitative and qualitative study of blood monocytes in patients with bronchogenic carcinoma

Summary Absolute circulating number and functions of blood monocytes (i.e., pinocytosis, phagocytosis, and chemotaxis) were studied in 25 patients with untreated bronchogenic carcinoma and in 28 control subjects. The absolute circulating monocyte count was increased in 20 (80%) of the patients. There was no difference in the pinocytic and phagocytic activity of patient and control monocytes. In contrast, patient monocytes showed depressed chemotactic responsiveness. This defect was more severe in small cell anaplastic carcinoma than in the other histologic types of bronchogenic carcinoma (P=0.001), and may explain the difference in macrophage infiltration seen in solid tumours of the lung. There was no correlation between chemotaxis and clinical stage. Depressed chemotaxis may be related to a plasma factor, since patient plasma inhibited the chemotaxis of control monocytes as well as the activity of chemotactic agents. The defective chemotaxis and the presence of plasma inhibitory activity may interfere with the ability of blood monocytes to accumulate as macrophages in tumour sites. Abbreviations used in this paper are: MCR, monocyte chemotactic response; SAC, small cell anaplastic bronchogenic carcinoma; OBC, non-small cell bronchogenic carcinoma MEM, Eagle's minimal essential medium; CFI, chemotactic factor inhibitor(s); HSA, human serum albumin     

Normalization of defective monocyte chemotaxis during chemotherapy in patients with small cell anaplastic carcinoma of the lung

Summary Monocyte chemotactic responsiveness (MCR) in 14 patients with small cell anaplastic bronchogenic carcinoma was depressed before treatment compared with the MCR in 28 normal controls (P=0.00004). MCR was subsequently monitored during combination chemotherapy and after 6 months the MCR had become normalized compared with pretreatment values (P=0.00006).In addition, chemotactic factor inhibitor (CFI) activity in plasma was measured before treatment and after 6 months. When incubated with plasma before treatment casein had 62% of normal activity and when incubated with plasma after chemotherapy, 81% of normal activity (P=0.0009). CFI activity decreased by greater amounts in patients in complete remission than in patients in partial remission or in non-responders (P=0.01). This study supports the concept that cancer patients have depressed monocyte function. Chemotherapy seems to enhance monocyte chemotaxis in vitro and to decrease CFI activity in plasma.     

Incidence of chromosome abnormalities in newborn children. Comparison between incidences in 1969–1974 and 1980–1982 in the same area

Summary As part of an ongoing study of the influence of environmental factors on pregnancy, childbirth, and fetuses, comparisons have been made between incidences in 1969–1974 and in 1980–1982 of chromosome aberrations in liverborn children in the same area of Denmark. The incidence of chromosome aberrations in the first period was 2.6 per 1000, compared with 4.1 per 1000 during the latter period. However, the difference was mainly due to an increase in inversions, and this in turn was due to a difference in chromosome staining methods between the two periods.It is concluded that the Danish study and similar studies in the United States, Canada, and Scotland indicate that early detection of chromosome aberrations by chromosome examination at birth is indicated in order to be able to inform and counsel parents of children with chromosome aberrations. Chromosome examination at birth is also of importance in the diagnosis of structural inheritable chromosome aberrations and consequent family investigation and genetic counseling.     

Computer analysis of two-dimensional gels

New methods and computer programs are described which enable one to analyze autoradiograms produced by two-dimensional gel electrophoresis. These programs are completely automatic with respect to finding spots resolved by such gels and quantitating the radioactivity in them. Semiautomatic programs have also been developed to match the spot patterns of different autoradiograms, and to follow the synthesis of any individual polypeptide through a series of gels.     

[3H]Propyl β-Carboline-3-Carboxylate Binds Specifically to Brain Benzodiazepine Receptors

Ethyl beta-carboline-3-carboxylate has recently been isolated from human urine and it was proposed that derivatives of this compound might be related to an endogenous ligand for benzodiazepine receptors. In the present study we investigated high-affinity binding of [3H]propyl beta-carboline-3-carboxylate ([3H]PrCC) to rat brain membranes. [3H]PrCC binds specifically and with high affinity (half-maximal binding at ca. 1nM) to rat brain membranes. The regional and subcellular distributions of specific [3H]PrCC binding are similar, but not identical, to the distributions of [3H]flunitrazepam or [3H]-diazepam binding. The total numbers of binding sites labelled by [3H]PrCC and [3H]flunitrazepam in rat cerebellum are closely similar, and both ligands bind to cerebellar membranes in a mutually exclusive way. The pharmacological selectivity of [3H]PrCC and [3H]diazepam binding is almost identical. Binding of [3H]PrCC like binding of [3H]diazepam, can be increased in vitro by muscimol, GABA and SQ 20.009. Although subtle differences in binding characteristics were observed, these results indicate that [3H]PrCC and benzodiazepines bind to a common recognition site on benzodiazepine receptors.