Search PubMed⌕ Search

Biomedical subjects

A Luini

Publications and source records attributed to A Luini.

At least 145 records · Page 8Linked to original sources
PubMed1985

Hormone secretagogues increase cytosolic calcium by increasing cAMP in corticotropin-secreting cells.

Corticotropin (ACTH)-releasing factor, vasoactive intestinal peptide, and catecholamines--hormones that stimulate ACTH secretion and cAMP generation--increased cytosolic calcium in AtT-20 cells. The increase in intracellular calcium is presumably a consequence of the stimulated cAMP synthesis, since forskolin, an activator of the catalytic unit of adenylate cyclase, and the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP) also increased the cytosolic levels of this ion. Pretreatment with somatostatin, a neuropeptide that inhibits stimulation of the adenylate cyclase system and the secretion of ACTH blocked the increase of cytosolic calcium. The effect of 8Br-cAMP, which bypasses the cyclase, was not inhibited by somatostatin pretreatment. The source of the increased calcium appears to be mainly extracellular. This is indicated by the inability of the secretagogues to increase cytosolic calcium in a medium deprived of this ion or in the presence of blockers of voltage-gated calcium channels. The involvement of calcium channels in the calcium rise evoked by the secretagogues was supported by experiments using the whole-cell patch-clamp technique. In these experiments 8Br-cAMP increased voltage-dependent calcium currents. These results suggest the following chain of events in the receptor-mediated elevation of cytosolic calcium and the concomitant release of ACTH from AtT-20 cells: hormone-receptor binding----cAMP synthesis----protein kinase activation----calcium channel activation----increase in cytosolic calcium----many steps----ACTH release. Phorbol myristate acetate, a compound which does not stimulate cAMP generation but enhances the release of ACTH in AtT-20 cells, decreased the cytosolic calcium level.

Adrenocorticotropic Hormone↗
PubMed1984

An evaluation of selected brain constituents as putative excitatory neurotransmitters.

Searching for the endogenous ligands of the 4 classes of excitatory amino acid receptors detected in the mammalian CNS, we have measured, using a 22Na+ efflux receptor assay, the excitatory activity of 42 brain constituents or analogs and established the receptor specificity of those substances which possess excitatory properties. Among the substances tested were methyltetrahydrofolate and N-acetylaspartylglutamate, two putative ligands of the kainate and glutamate receptors. These compounds were found to have very little or no excitatory activity, respectively. The 8 brain constituents possessing excitatory properties displayed a receptor specificity similar to either that of N-methyl-D-aspartate (e.g. quinolinate) or glutamate (e.g. cysteine sulfinate) but not of kainate or quisqualate. These results are discussed in relation with the problem of the identification of brain excitatory neurotransmitters.

Animals↗
PubMed1984

Differential sensitivity of selected rat brain areas to excitatory neurotransmitters released by K+ depolarization.

The depolarization of brain slices by high K+ concentrations in the presence of Ca2+ ions leads to the release from nerve terminals of endogenous excitatory neurotransmitters that interact with subsynaptic receptors controlling the neuronal membrane permeability to Na+ ions. This interaction has been studied by following the K+-evoked Ca2+-dependent 22Na+ efflux from 22Na+-preloaded slices from the cortex, striatum, hippocampus, cerebellum, substantia nigra and hypothalamus of the rat. The results indicate that the so-called N-methyl-D-aspartate receptor mediates the bulk of the excitatory transactions in the cortex and striatum whereas a subsynaptic glutamate receptor may mediate those in the hippocampus and cerebellum.

Animals↗
PubMed1984

Barbiturates, alcohols and the CNS excitatory neurotransmission: specific effects on the kainate and quisqualate receptors.

The effects of barbiturates and straight-chain aliphatic alcohols on the responses of rat striatal neurons to excitatory amino acids have been investigated. The responses to N-methyl-D-aspartate, quisqualate, kainate, L-glutamate and L-aspartate were measured by the increase in 22Na+ efflux rate that they produce in brain slices. The responses to quisqualate and kainate, measured in the 22Na+ efflux assay, were found to be partially blocked by barbiturates whereas the responses to N-methyl-D-aspartate, glutamate and aspartate were not. The kainate and quisqualate-induced increases in 22Na+ efflux rate were much more readily blocked by the presence of aliphatic alcohols than were the responses to N-methyl-D-aspartate, glutamate and aspartate. These results strengthen the idea of the existence of 4 distinct receptors for excitatory amino acids in the rat striatum. They are consistent with the presence on the kainate and quisqualate receptors, but not on the N-methyl-D-aspartate and glutamate/aspartate receptors of a hydrophobic domain which would provide a site of interaction for barbiturates and alcohols. They suggest that receptors for excitatory amino acids can be targets for the actions of barbiturates and alcohols on the central nervous system, and may mediate some of the anesthetic and hypnotic effects of these drugs.

Alcohols↗
PubMed1983

Differential sensitivity of selected brain areas to excitatory amino acids.

The 22Na+ efflux stimulated by selected agonists of the 4 excitatory amino acid receptors, previously detected in the striatum, has been studied on 22Na+-preloaded slices prepared from 10 major areas of the rat brain. All brain areas were found to be sensitive, albeit to varying extents, to excitatory amino acids. The cerebellum was exceptional in its high sensitivity to kainate and quisqualate and in the absence of effect of N-methyl-D-aspartate. These results support the suggestion that excitatory amino acids interact with heteregenous receptors which differ from each other not only in their pharmacological properties but also in their regional distribution.

Amino Acids↗
PubMed1983

Presence of N-methyl-D-aspartate-like and kainate-like activities in bovine brain.

Searching for the natural ligands interacting with brain excitatory amino acid receptors, we have isolated from cow brain a low-Mr ampholyte fraction containing molecules with excitatory properties similar to those of N-methyl-D-aspartate and kainate, which cannot be accounted for by any of the known brain excitants. This finding supports the hypothesis of the existence of excitatory neurotransmitters other than L-glutamate and L-aspartate.

Animals↗
PubMed1983

Comments on a series of 88 invasive microcarcinomas of the breast.

Eighty-eight women with minimal invasive breast cancer were treated at the Istituto Nazionale Tumori of Milan, in the decade 1970-1980. Their tumors were smaller than 0.5 cm in diameter and were clinically assessed as T1N0M0; surgery, consisting of radical or limited procedures, was performed, always with complete axillary dissection. Pathologic assessment showed that axillary lymph nodes presented with metastases in 21.5% of cases. In 1 of N-positive cases, more than 3 nodes were affected, and in 5 cases extracapsular invasion was observed. Five-year actuarial survival, calculated by the life table method, was as high as 90%, demonstrating that these have a favorable prognosis, even when they are treated by limited surgery followed by radiotherapy on the residual breast, provided that the axilla is completely dissected. Minimal invasive breast cancer should consequently be clearly distinguished from other pathologic entities termed as "minimal", such as lobular carcinoma in situ and intraductal carcinoma, for which complete axillary dissection is not worthwhile.

Adult↗
PubMed1983

Bicyclic lactones derived from kainic acid as novel selective antagonists of neuroexcitatory amino acids.

The bicyclic [2S-(2 alpha,3 beta,4 beta)]-2-carboxy-4-(1-hydroxy-1-methylethyl)-3- pyrrolidineacetic acid delta-lactone (4), as well as its 4-[1-hydroxy-1-(iodomethyl)ethyl], 4-[1-hydroxy-1-(hydroxymethyl)ethyl], and 4-[1-hydroxy-1-[(phenyl-thio)methyl]ethyl] analogues, 6, 7, and 9, respectively, were designed and synthesized as potential selective antagonists of neuroexcitatory amino acids. When applied to rat brain slices, these lactones, which are chemically derived from kainic acid, inhibit the stimulation of Na+ fluxes induced by the neuroexcitants kainic acid and N-methyl-D-aspartic acid. Lactone 4 and the hydroxy lactone 7 block preferentially the response to N-methyl-D-aspartic acid, while the iodo lactone 6 and the phenylthio lactone 9 are mainly kainic acid antagonists. Total inhibitions can be obtained, half of the maximal effect being observed at lactone concentrations in the range of 0.2-3 mM.

Amino Acids↗
PubMed1982

Secondary lung cancer resection with curative intent: causes of success and failure and prognostic factors.

Observed and disease-free survivals were evaluated in a consecutive series of 46 resections of pulmonary metastases, with major chance of being a unique phenomenon. Survival curves were computed both since the treatment of primary tumors and since resection of lung metastases. From the treatment of primary tumors, median disease-free interval was 33 months, and rose to 66 months after resection of lung metastases. From the treatment of secondary lung cancers the observed survivals at 1, 3 and 5 years were respectively 60%, 41% and 26%. Survival was clearly affected by development and resectability of post-thoracotomic recurrence (100% without recurrence, 50% with resectable recurrence and 4% with unresectable recurrence). Recurrence rate was related to the first disease-free interval and to the anatomical extent (particularly for nodal status) of secondary lung cancer. This fact suggests that the failure of secondary lung cancer resection may arise either from the primary cancer (poor selection) or from the secondary cancer (delay in treatment).

Adolescent↗
PubMed1981

The stimulation of ion fluxes in brain slices by glutamate and other excitatory amino acids.

The stimulation of ion movements by excitatory amino acids in brain slices allows the study of various events related to the process of excitatory neurotransmission. Presynaptic mechanisms of uptake of putative neurotransmitters can be followed by the influx of Na+ ions. Postsynaptic depolarizations due to the activation of action potentials or of ionophores associated with specific receptors can be monitored by measurements of the rate of efflux of radioactive tracer ions. Thus, the pharmacological properties of the excitatory amino acid receptors can be investigated as well as those of their putative endogenous effectors.

Action Potentials↗
PubMed1981

Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast.

From 1973 to 1980, we carried out a controlled study at the National Cancer Institute in Milan to consider the value of a conservative procedure in patients with breast cancer of small size. We randomized 701 patients with breast cancer measuring less than 2 cm in diameter and with no palpable axillary lymph nodes to Halsted radical mastectomy or to "quadrantectomy" with axillary dissection and radiotherapy to the ipsilateral residual breast tissue. We treated 349 patients with Halsted mastectomy and 352 with quadrantectomy. The two groups were comparable in age distribution, size and site of primary tumor, menopausal status, and frequency of axillary metastases. There were three local recurrences in the Halsted group and one in the quadrantectomy group. Actuarial curves showed no difference between the two groups in disease-free or overall survival. From these results, mastectomy appears to involve unnecessary mutilation in patients with breast cancer of less than 2 cm and no palpable axillary nodes.

Aged↗
PubMed1981

Lactones derived from kainic acid: novel selective antagonists of amino acid-induced Na+ fluxes in rat striatum slices.

The effects of amino acid lactones chemically derived from the neuroexcitant kainic acid on the response of rat striatal slices to excitatory amino acids, were studied. These compounds antagonize to varying extents the effects of kainic acid and N-methyl-D-aspartic acid but have no effect on the responses to glutamic or quisqualic acid. Some of the lactones antagonize preferentially the effects of kainic acid. This study further confirms the existence of heterogenous populations of excitatory amino acid receptors in the rat striatum.

Amino Acids↗
PubMed1981

Distinct pharmacological properties of excitatory amino acid receptors in the rat striatum: study by Na+ efflux assay.

Specific 22Na+ efflux rates from preloaded rat striatal slices are increased in a dose-dependent manner by L-glutamate and other excitatory amino acids displaying the following order of efficiency: N-methyl-D-aspartate greater than DL-homocysteate greater than quisqualate greater than kainate greater than D-glutamate greater than L-glutamate greater than L-aspartate. Amino acid antagonists such as 2-amino-5-phosphonovalerate, gamma-D-glutamylglycine, DL-aminosuberate, DL-aminoadipate, and diethyl glutamate but not nonexcitatory amino acids such as gamma-aminobutyric acid inhibit the amino acid-induced increase in specific 22Na+ efflux rate. Increased K+ concentrations, in the presence of 2 mM Ca2+, increase the specific 22Na+ efflux. The latter and the response to N-methyl-D-aspartate, but not the responses to L-glutamate, L-aspartate, quisqualate, and kainate, are inhibited to similar extents by the same antagonists. These results suggest the release from striatal nerve terminals of a putative neurotransmitter with pharmacological properties different from those of L-glutamate or L-aspartate but similar to those of N-methyl-D-aspartate. The results of this study show that the stimulation of the 22Na+ efflux in brain slices by neuroactive amino acids and K+ ions is a valid and powerful tool for pharmacological investigations of excitatory amino acid receptors and their putative ligands.

Amino Acids↗