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Hugoniot data of plastic foams obtained from laser-driven shocks.

In this paper we present Hugoniot data for plastic foams obtained with laser-driven shocks. Relative equation-of-state data for foams were obtained using Al as a reference material. The diagnostics consisted in the detection of shock breakout from double layer Al/foam targets. The foams [poly(4-methyl-1-pentene) with density 130 > rho > 60 mg/cm3] were produced at the Institute of Laser Engineering of Osaka University. The experiment was performed using the Prague PALS iodine laser working at 0.44 microm wavelength and irradiances up to a few 10(14) W/cm2. Pressures as high as 3.6 Mbar (previously unreached for such low-density materials) where generated in the foams. Samples with four different values of initial density were used, in order to explore a wider region of the phase diagram. Shock acceleration when the shock crosses the Al/foam interface was also measured.

Journal Article↗

Immunogenicity of HILDA/LIF either in a soluble or in a membrane anchored form expressed in vivo by recombinant vaccinia viruses.

Insertion of various cDNAs in the genome of the vaccinia virus (VV) enables the in vivo and in vitro study of the functional role and/or the immunogenicity of the virally encoded recombinant proteins. We have prepared a recombinant VV expressing the cDNA of the human cytokine HILDA/LIF (human interleukin for DA cells/leukaemia inhibitory factor), and used this virus to immunize mice against this protein, which is very homologous to its murine counterpart (approximately 80% homology). We also constructed and expressed by the same system a chimeric gene encoding the HILDA/LIF protein fused to the 37 COOH-terminal amino-acids of the human decay accelerating factor (DAF). This sequence proved to be sufficient for the targeting of the fusion protein to the cell membrane, where it is linked to the phosphatidylinositols. Both recombinant VVs induced cytokine-specific antibodies in mice as analysed with an ELISA where the recombinant HILDA/LIF was plastic-coated and a cytofluorometric assay where the LIF-DAF molecule was present at the cell surface of stably transfected P815. In the latter case HILDA/LIF remained biologically active suggesting that it was expressed in its native form. The LIF-DAF fusion protein was found to exhibit a better capacity to elicit an antibody response against the native form of the cytokine as detected in cytofluorometric assays. Whatever the recombinant virus used to immunize the mice, the MoAbs obtained were positive either in the ELISA or in the cytofluorometric assays but one, which suggested that the plastic coating induced a conformational change of HILDA/LIF.

Animals↗

HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.

Wild-type RAS family members determine the signaling and therapeutic response in cancers driven by mutant HRAS and KRAS because they activate alternate RAS effector pathways. Here, we found that the requirement for wild-type RAS to support mutant NRAS-driven transformation correlated with codon-specific differences in GTP hydrolysis. NRAS with mutations at either Gly12 (G12X) or Gly13 (G13X), which retained the GDP-GTP cycling function, had modest autonomous transforming potential. In contrast, NRAS with GTP-locking mutations at Gln61 (Q61X mutants) was uncoupled from receptor tyrosine kinase (RTK) input, rendering wild-type RAS an obligate partner for RTK-stimulated signaling and oncogenesis. In RASless cells expressing mutant NRAS, reintroduction of wild-type HRAS was sufficient to restore signaling and transformation. Global dependency mapping in human cancer cells revealed functional partitioning, wherein mutant NRAS promoted MAPK signaling and wild-type HRAS promoted PI3K-AKT survival signaling. Consequently, allele-specific or pan-RAS(ON) inhibitors synergized with inhibitors of proximal RTK signaling or of wild-type HRAS or KRAS to overcome this signaling plasticity. Pan-RAS(ON) and HRAS inhibition was synergistic for all NRAS mutants tested, with Q61X mutants showing greater sensitivity. These findings define the signaling partnership between mutant NRAS and wild-type HRAS as a targetable vulnerability and provide a biochemical blueprint for dual RAS inhibition in NRAS-mutated malignancies.

Humans↗

Molecular psychology: roles for the ERK MAP kinase cascade in memory.

In this review we describe an emerging understanding of the roles of the Extracellular-signal regulated kinase/mitogen-activated protein kinase (ERK/MAPK) cascade in learning and memory. We begin by describing several behavioral memory paradigms and review data implicating ERK as an essential component of the signal transduction mechanisms subserving these processes. We then describe evidence implicating ERK as a critical player in synaptic and neuronal plasticity-a cellular role likely to underlie ERK's behavioral role in the animal. We then proceed to parsing the complexities of biochemical regulation of ERK in neurons and to a description of a few likely cellular targets of ERK. This is in order to begin discussing the possible molecular basis of ERK-mediated behavioral change. We close our review with speculations concerning how the complexities and idiosyncrasies of ERK regulation may allow for sophisticated information processing at the biochemical level in neurons-attributes that may make the ERK cascade well-suited for triggering complex and long-lasting behavioral change. Our goal in this review is not so much to portray ERK as unique regarding its role as a signal transducter in memory, but rather to use ERK as one specific example of recent studies beginning to address the molecules and signal transduction pathways subserving cognition.

Animals↗

Altered hippocampus synaptic function in selenoprotein P deficient mice.

Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS.

Journal Article↗

Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions.

Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3.

Animals↗

[Mesenchymal stem cells transduced by PLEGFP-N1 retroviral vector maintain their biological features and differentiation].

BACKGROUND: Enhanced green fluorescent protein (EGFP) has been an important reporter gene for gene therapy. Human mesenchymal stem cells (hMSCs) are ideal target cells in cell transplantation and tissue engineering. We investigated their biological characteristics and differentiation mediated by PLEGFP-N1 retroviral transduction. METHODS: hMSCs were isolated from human bone marrow by density gradient fractionation and adherence to plastic flasks. Individual colonies were selected and cultured in tissue dishes. Packaging cells PT67 were transfected by PLEGFP-N1 retroviral vector, and hMSCs were transduced by viral supernatant infection. Meanwhile, hMSCs-EGFP were identified by immune phenotypes and whether it could differentiate into osteoblasts or adipocytes under conditioned media was investigated. RESULTS: The rate of stably transduced hMSCs-EGFP was up to 96% after being screened by G418. hMSCs-EGFP exhibited fibroblast-like morphological features. Flow cytometric analyses showed that hMSCs-EGFP were positive for CD73, CD105, CD166, CD90 and CD44, but negative for CD34 and CD45. In addition, it could functionally be induced into osteocytes or adipocytes under conditioned media. These biological features of hMSCs-EGFP were consistent with those of hMSCs. CONCLUSIONS: hMSCs transduced by PLEGFP-N1 retroviral vector can be used in vivo securely because they can maintain their biological characteristics and differentiation. It is a simple and reliable way to trace the changes of hMSCs in vivo by EGFP during cell transplantation and gene therapy.

Cell Cycle↗

[Treatment by non-physicians of skin diseases--including potentially malignant diseases with lasers and intense pulsed light].

INTRODUCTION: Laser and IPL treatment by non-physicians raises professional concern. The purpose of this investigation is to evaluate laser and IPL treatment carried out by non-physicians and to assess the level of pre-treatment information given to patients. MATERIAL AND METHODS: Approached clinics were found by internet-searches and from advertisements in telephone directories and national newspapers. The target group was clinics in Zealand that offer laser or IPL treatment of pigmented lesions, pigmented nevi, sun-damaged skin, acne and/or unwanted hair growth. The investigation did not include specialised clinics run by dermatologists and plastic surgeons. By means of anonymous telephone calls the clinics were presented for standardized questions under the pretext of being a potential client. RESULTS: Of 28 clinics investigated, 93% offered treatment for unwanted hair growth, 75% for pigmented lesions, 50% for acne, 36% for possible actinic keratoses and 29% for pigmented nevi. Medical examination was an exception (11%). In none of the clinics were medical examinations performed by specialists in dermatology or plastic surgery. Cosmeticians or nurses generally gave the laser and IPL treatments. In 57% of the clinics patients were informed that the treatment did not have any risks. In June treatment was offered in 79% of the clinics, 18% of which mentioned that no special precautions were necessary when treating in sunny periods. CONCLUSION: Laser and IPL treatment of skin diseases, including potential malignant diseases, is carried out by non-physicians and pre-treatment information contains major errors and shortcomings.

Clinical Competence↗

Amino acids as the source of considerable excitation in cerebral cortex.

A number of different factors contributed to the rationale for providing a critical review of the field of excitatory amino acids in the cerebral cortex at this time. In addition to the recent growing realisation by clinicians that the excitatory amino acids are linked critically to a number of neurological conditions, including neurodegenerative syndromes such as Alzheimer's disease, cortical damage due to stroke and cerebral ischemia, epilepsy, amyotropic lateral sclerosis, and schizophrenia, the recent cloning and membrane reconstitution of specific receptors known as AMPA, NMDA, kainate, and metabotropic receptors and their known subunits have prompted a surge of renewed interest in this important family of synaptic transmitter molecules. Moreover, recent advances in our understanding of the molecular events involved in growth promotion in the early stages of the development of the cortex have shown that both NMDA and non-NMDA receptor subtypes perform important roles in certain aspects of target selection and neurite outgrowth, in cone stimulation and guidance, and in spine formation and morphological alterations. A recent explosive growth in interest in the possible roles of nitric oxide and related short-lived radicals in plasticity, disease, and synaptic transmission also is related closely with the actions of excitatory amino acids. All these relatively new advances have transpired in parallel with ongoing work that has extended our appreciation for the roles of excitatory amino acids in the areas of synaptic plasticity (long-term potentiation, long-term depression, receptive field reorganisation following drug-induced or peripheral sensory disturbances, such as denervation or amputation), in processes of normal transmission at functionally and electrophysiologically identified neurones of the cerebral cortex, and in distinct proposed roles for cortical glia. A greater appreciation of the diverse types and properties of the burgeoning family of receptors for the metabotropic receptor also contributed to our desire to feature that aspect of the field in the context of glia and neurones of the cerebral cortex. That part of the field of neuroscience concerned with the functions of excitatory amino acids has grown so large over the past 10 years or so, that a review paper focusing on the contributions to a specialized meeting devoted solely to cerebral cortex could easily be supported by material comprising a sufficient body of communications from top-quality research laboratories. The present account endeavours to summarize and discuss the biochemical characteristics, physiological roles, pharmacological properties, clinical relevance, developmental involvements, and anatomical-morphological aspects pertaining to the excitatory amino acid transmitters in cerebral cortex.

Animals↗

Heterogeneity and selective targeting of neuronal nicotinic acetylcholine receptor (nAChR) subtypes expressed on retinal afferents of the superior colliculus and lateral geniculate nucleus: identification of a new native nAChR subtype alpha3beta2(alpha5 or beta3) enriched in retinocollicular afferents.

The activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been implicated in the activity-dependent development and plasticity of retina and the refinement of retinal projections. Pharmacological and functional studies have also indicated that different presynaptic nAChRs can have a modulatory function in retinotectal synapses. We biochemically and pharmacologically identified the multiple nAChR subtypes expressed on retinal afferents of the superior colliculus (SC) and lateral geniculate nucleus (LGN). We found that the alpha6beta2(*) and alpha4(nonalpha6)beta2(*) nAChRs are the major receptor populations expressed in both SC and LGN. In addition, the LGN contains two minor populations of alpha2alpha6beta2(*) and alpha3beta2(*) subtypes, whereas the SC contains a relatively large population of a new native subtype, the alpha3beta2(alpha5/beta3) nAChR. This subtype binds the alpha-conotoxin MII with an affinity 50 times lower than that of the native alpha6beta2(*) subtype. Studies of tissues obtained from eye-enucleated animals allowed the identification of nAChRs expressed by retinal afferents: in SC alpha6beta2(*), alpha4alpha6beta2(*), and alpha3beta2(*) (approximately 45, 35, and 20%, respectively), in LGN, alpha4alpha6beta2(*), alpha6beta2(*), alpha4beta2(*), alpha2alpha6beta2(*), and alpha3beta2(*) (approximately 40, 30, 20, 5, and 5%, respectively). In both regions, more than 50% of nAChRs were not expressed by retinal afferents and belonged to the alpha4beta2(*) (90%) or alpha4alpha5beta2(*) (10%) subtypes. Moreover, studies of the SC tissues obtained from wild-type and alpha4, alpha6, and beta3 knockout mice confirmed and extended the data obtained in rat tissue and allowed a comprehensive dissection of the composition of nAChR subtypes present in this retinorecipient area.

Amino Acid Sequence↗

Induction of MAP1B phosphorylation in target-deprived afferent fibers after kainic acid lesion in the adult rat.

We have previously shown that the phosphorylated form of microtubule-associated protein 1B (MAP1B-P), which is located in growing axons during development and regeneration, remains detectable in the adult central nervous system only in areas that undergo morphologic plasticity (Nothias et al. [1996] J. Comp. Neurol. 368:317-334). Our objective in the present study was to determine whether lesion-induced axonal remodeling, in the adult rat, is associated with reinduction of MAP1B phosphorylation. MAP1B-P was not detectable in intact adult thalamic ventrobasal complex (VB), although low levels of MAP1B and its mRNA were present. A neuron-depletion of VB by in situ injection of kainic acid was followed by an induction of MAP1B phosphorylation by 24 hours postlesion. MAP1B-P was detected in fibers originating from undamaged neurons that were not located in the lesion, as demonstrated by the absence of hybridized MAP1B-mRNA. Ultrastructural analysis confirmed the exclusive location of MAP1B-P in axons in a proximodistal gradient. MAP1B phosphorylation appeared to be regulated by posttranslational modification of existing protein because the levels of MAP1B-mRNA did not change. The number of MAP1B-P-labeled fibers increased during the first month postlesion and remained high for a long period. Double staining by using axonal tracing with dextran-biotin and tyrosine hydroxylase immunohistochemistry, showed the presence of MAP1B-P in VB afferents from somatosensory relays and the locus coeruleus. This study supports the hypothesis that MAP1B, at a particular state of phosphorylation, is correlated with axonal remodeling in the adult central nervous system (CNS). We suggest that the interaction of MAP1B-P with microtubules allows the modulation of their dynamic properties during periods of increased axonal plasticity.

Afferent Pathways↗

Regulation of the neuronal proteasome by Zif268 (Egr1).

Most forms of neuronal plasticity are associated with induction of the transcription factor Zif268 (Egr1/Krox24/NGF-IA). In a genome-wide scan, we obtained evidence for potential modulation of proteasome subunit and regulatory genes by Zif268 in neurons, a finding of significance considering emerging evidence that the proteasome modulates synaptic function. Bioinformatic analysis indicated that the candidate proteasome Zif268 target genes had a rich concentration of putative Zif268 binding sites immediately upstream of the transcriptional start sites. Regulation of the mRNAs encoding the psmb9 (Lmp2) and psme2 (PA28beta) proteasome subunits, along with the proteasome-regulatory kinase serum/glucocorticoid-regulated kinase (SGK) and the proteasome-associated antigen peptide transporter subunit 1 (Tap1), was confirmed after transfection of a neuronal cell line with Zif268. Conversely, these mRNAs were upregulated in cerebral cortex tissue from Zif268 knock-out mice relative to controls, confirming that Zif268 suppresses their expression in the CNS. Transfected Zif268 reduced the activity of psmb9, SGK, and Tap1 promoter-reporter constructs. Altered psmb9, SGK, and Tap1 mRNA levels were also observed in an in vivo model of neuronal plasticity involving Zif268 induction: the effect of haloperidol administration on striatal gene expression. Consistent with these effects on proteasome gene expression, increased Zif268 expression suppressed proteasome activity, whereas Zif268 knock-out mice exhibited elevated cortical proteasome activity. Our findings reveal that Zif268 regulates the expression of proteasome and related genes in neuronal cells and provide new evidence that altered expression of proteasome activity after Zif268 induction may be a key component of long-lasting CNS plasticity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Synapse formation in the olfactory cortex by regenerating optic axons: ultrastructural evidence for polyspecific chemoaffinity.

The optic nerve was severed at its entry into the optic chiasma and implanted into the striatal region of the ipsilateral cerebral hemisphere in adult frogs (Rana pipiens). Regenerating retinal ganglion cell axons, observed by the autoradiographic tracing method and by horseradish peroxidase (HRP) fiber filling, grew anteriorly along the olfactory tracts and posteriorly along the ipsilateral lateral forebrain bundle and stria medullaris. Many of the regenerating axons ultimately joined the ipsilateral optic tract. The optic axons formed terminal plexuses in the olfactory cortex, lateral geniculate complex, pretectum, tectum, and basal optical nucleus but not in the amygdala or other cerebral territories not postsynaptic to the olfactory bulb, nor in the cell groups associated with the lateral forebrain bundle or stria medullaris. Optic axon terminals labeled with HRP were observed by electron microscopy in the ipsilateral olfactory cortex and in the normal projection areas of the optic nerve, although they were misplaced to the ipsilateral side. They contained clear, spherical synaptic vesicles and pale mitochondria and made Gray type I, asymmetric contacts on dendrites. The retinal projection to the olfactory cortex was formed early in regeneration and was maintained to some degree for periods up to 39 weeks. It was absent in a specimen surviving 50 weeks. Retinal innervation appeared earlier in the lateral geniculate complex and pretectum than in the tectum. These observations suggest that regenerating retinal ganglion cell axons have an affinity for neurons in the olfactory cortex, as well as for the neurons in the optic pathway to which they are normally postsynaptic. Unless the apparent selectivity of the aberrant projection is regulated by principles other than those that bring about the reinnervation of the normal optic centers, the data further suggest that the nature of the molecular mechanisms conveying synaptic specificity must be broad enough to permit the formation of limited sets of alternative synaptic connections. The ability to innervate selectively targets other than those normally specified is termed, here, polyspecificity. Since polyspecificity refers to the the affinity of retinal ganglion axons, as a class, for target structures considered as unit aggregates, it is conceptually different from the graded affinity of ganglion cells in different regions of the retina for target neurons in different regions of the tectum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Target dependence of hypoglossal motor neurons during development in maturity.

We have investigated the target dependence of hypoglossal motor neurons in postnatal rats by transecting the hypoglossal nerve and preventing reinnervation of the tongue. After transection in early postnatal life, approximately 60% of hypoglossal motor neurons die and surviving neurons are markedly atrophic compared to contralateral controls. In maturity, there is also substantial neuronal atrophy and about 30% of motor neurons appear to die after the procedure. However, most hypoglossal neurons in adults survive transection for periods up to 1 year. The adult response is present by 3 weeks of age. The time course of neuronal atrophy and death after permanent target deprivation was investigated in adult animals. One month after the hypoglossal nerve was deflected, there was marked axonal atrophy, although somatic atrophy was minimal. By 3 months after the procedure substantial neuronal atrophy and apparent cell loss (about 30%) had occurred. There was little change between 3 and 6 months. We conclude that hypoglossal motor neurons are influenced by connections with their targets in postnatal life. Even in maturity, neurons require target connections for maintenance of axonal and somatic morphology. However, the majority of motor neurons in adult animals can survive target deprivation for prolonged periods.

Aging↗

Cre-mediated cerebellum- and hippocampus-restricted gene mutation in mouse brain.

Using the phage P1-derived Cre/loxP recombination system, we have created a line of cre-transgenic mice in which the Cre-mediated gene deletion is restricted to granule cells of cerebellum and dentate gyrus of hippocampus. Low levels of deletion were also present in pyramidal cells of hippocampal CA1 and CA3 fields. The Cre/loxP recombination occurred prenatally. The recombination efficiencies in the granular layer of the cerebellum, the granular layer of the dentate gyrus, and the CA1 and CA3 pyramidal cells of the hippocampus were 34.0%, 23.1%, 3.0%, and 9.8%, respectively. This line of cre-transgenic mice should be conducive to studies of the effect of a gene mutation upon brain development and plasticity.

Animals↗

The tripartite synapse: roles for gliotransmission in health and disease.

In addition to being essential supporters of neuronal function, astrocytes are now recognized as active elements in the brain. Astrocytes sense and integrate synaptic activity and, depending on intracellular Ca(2+) levels, release gliotransmitters (e.g. glutamate, d-serine and ATP) that have feedback actions on neurons. Recent experimental results have raised the possibility that quantitative variations in gliotransmission might contribute to disorders of the nervous system. Here, we discuss targeted molecular genetic approaches that have demonstrated that alterations in protein expression in astrocytes can lead to serious changes in neuronal function. We also introduce the concept of 'astrocyte activation spectrum' in which enhanced and reduced gliotransmission might contribute to epilepsy and schizophrenia, respectively. The results of future experimental tests of the astrocyte activation spectrum, which relates gliotransmission to neurological and psychiatric disorders, might point to a new therapeutic target in the brain.

Adenosine Triphosphate↗

The multifarious hippocampal mossy fiber pathway: a review.

The hippocampal mossy fiber pathway between the granule cells of the dentate gyrus and the pyramidal cells of area CA3 has been the target of numerous scientific studies. Initially, attention was focused on the mossy fiber to CA3 pyramidal cell synapse because it was suggested to be a model synapse for studying the basic properties of synaptic transmission in the CNS. However, the accumulated body of research suggests that the mossy fiber synapse is rather unique in that it has many distinct features not usually observed in cortical synapses. In this review, we have attempted to summarize the many unique features of this hippocampal pathway. We also have attempted to reconcile some discrepancies that exist in the literature concerning the pharmacology, physiology and plasticity of this pathway. In addition we also point out some of the experimental challenges that make electrophysiological study of this pathway so difficult.Finally, we suggest that understanding the functional role of the hippocampal mossy fiber pathway may lie in an appreciation of its variety of unique properties that make it a strong yet broadly modulated synaptic input to postsynaptic targets in the hilus of the dentate gyrus and area CA3 of the hippocampal formation.

Animals↗

Gigantomastia.

A case of gigantomastia is reported. The breast enlargement started some years before first pregnancy, during which a tremendous acceleration was observed. Various laboratory investigations elicited normal values, except for some high values of prolactin. No treatment was given. After delivery, the patient nursed her baby. Thirteen weeks later, lactation was inhibited with bromocriptine. A further 3 weeks later, a reduction mammoplasty was performed. One year later, the prolactin values were still normal. The etiology of this disease is not known. One possible explanation is an increased number or increased sensitivity of prolactin receptors in the target organ.

Adult↗