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Biomedical subjects

C Romano

Publications and source records attributed to C Romano.

At least 145 records · Page 8Linked to original sources
PubMed1996

Ultrastructural localization suggests that retinal and cortical inputs access different metabotropic glutamate receptors in the lateral geniculate nucleus.

Glutamate has an important neuromodulatory role in synaptic transmission through metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein-coupled second messenger pathways. Activation of these receptors on relay cells in the lateral geniculate nucleus (LGN) with the agonist trans-(1S,3R)-1-amino-1, 3-cyclopentanedicarboxylic acid produces a membrane depolarization that inactivates the low-threshold Ca2+ spike, causing a transition from burst to tonic response mode. The excitatory effects of metabotropic receptor activation in the LGN appear to be produced through the receptors linked to phosphoinositide hydrolysis and apparently only through activation of the corticogeniculate pathway. Two mGluRs, mGluR1alpha (a splice variant of mGluR1) and mGluR5, are linked to the phosphoinositide system. We examined the localization of these receptors with affinity-purified, anti-peptide, polyclonal antibodies raised to the C-terminal region of each receptor protein. Under examination with the light microscope, we found that both types of receptors are present in the geniculate neuropil and in that of the overlying thalamic reticular nucleus, including the perigeniculate nucleus. We also examined the ultrastructural localization of immunolabel with the electron microscope, using a postembedding immunogold marker to identify terminals, dendrites, and somata that contain GABA. Label for the antibody directed against mGluR1alpha was primarily localized in the dendrites of relay cells, postsynaptic to various terminal types. Of these, terminal profiles normally associated with corticogeniculate inputs predominated, whereas retinal terminal profiles were scarce. Label for the antibody directed against mGluR5 label was prominent in inhibitory F2-terminal profiles associated with the retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were localized to dendrites. The distribution of the two phosphoinositide-linked mGluRs in the LGN suggests very different functional roles for the two receptor types. We conclude from these data that mGluR1 appears to have a dominant role in corticogeniculate control of response mode through the feedback glutamatergic pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate activation of relay cells through feed forward glomerular interactions.

Afferent Pathways↗
PubMed1996

Metabotropic glutamate receptor 5 is a disulfide-linked dimer.

The sequences of the metabotropic glutamate receptors (mGluRs) show little homology with other members of the G protein-coupled receptor family and exhibit several distinctive features, including a large N-terminal extracellular domain with 17 cysteines in conserved positions. Here we demonstrate that mGluR5, as well as other mGluRs, behave as species approximately twice as large as expected from their sequence, but reducing conditions cause a decrease to the predicted molecular mass. Co-immunoprecipitation experiments using wild type and epitope-tagged receptors demonstrate that this is due to specific, disulfide-dependent dimerization of the receptor. The intermolecular disulfide that mediates dimerization occurs in the extracellular domain, within about 17 kDa from the N terminus.

Amino Acid Sequence↗
PubMed1996

Enhanced early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain: protein, mRNA splice variants, and regional distribution.

Glutamate stimulates phosphatidyl inositol hydrolysis and mobilizes intracellular calcium through the mediation of metabotropic glutamate receptors (mGluRs), in particular the "Group I" receptors mGluRs, mGluR1, and mGluR5. This activity is markedly enhanced in developing brain relative to the adult. To determine whether this may be due to an increased amount of mGluR5 present in the developing brain, we examined mGluR5 expression using western blotting to measure mGluR5 protein reverse transcription polymerase chain reaction (RT-PCR) to measure mGluR5 mRNA, and immunocytochemistry to assess the regional distribution of mGluR5 morphologically. Western blotting revealed that in all brain regions examined there is more mGluR5 protein present in developing brain than in the adult. In most regions, the developmental decrease was over two-fold. Total mGluR5 mRNA also decreased with development in most regions, but to a much lesser extent than the protein, suggesting that there is considerable post-transcriptional regulation of the expression of this receptor. RT-PCR analysis also demonstrated that in most regions the mGluR5a splice variant is most abundant in the young animals but mGluR5b predominates in the adult. Light microscopic immunocytochemistry indicated that expression is widespread in developing brain, and that the developmental decrease in receptor concentration is due to both an increased growth of receptor-poor tissue regions and decreased expression within receptor-rich regions.

Animals↗
PubMed1996

Immunocytochemical localization of polyamines in the tiger salamander retina.

The polyamines spermine and spermidine are present in neural tissue, but their functions there are not well understood. Recent work suggests that the NMDA subtype of glutamate receptors, other glutamate receptor subtypes, and certain K(+)-channels, are neural targets for polyamines. To better understand the neuron-specific roles of polyamines, we have developed antibodies that interact with spermine and spermidine in aldehyde-fixed tissue and used these antibodies in immunocytochemical studies to determine the cellular localization of these polyamines in the tiger salamander retina. The affinity-purified, polyclonal antibodies were highly specific for spermine and spermidine, exhibiting < 1% cross reactivity with putrescine, and virtually no cross-reactivity with GABA, arginine, lysine, or glutaraldehyde. Polyamine labeling was most abundant in cells in the inner half of the inner nuclear layer and in the ganglion cell layer. Some cells in the outer half of the inner nuclear layer are labeled, and there was some labeling in both synaptic layers. Double-labeling experiments indicated (1) all GABAergic amacrine cells were polyamine-positive; and (2) all ganglion cells (identified by back-filling after microinjections of rhodamine in the optic nerve) were polyamine-positive. These results are consistent with a role for polyamines as modulators of NMDA receptor function and channel function in the inner retina.

Animals↗
PubMed1996

Spermidine release from xenopus oocytes. Electrodiffusion through a membrane channel.

The mechanism of spermidine release from Xenopus oocytes was examined by measuring release of radioactive [3H]spermidine under different ionic conditions, and under voltage-clamp. In normal solution (2 mM K+), the efflux rate is less than 1% per hour, and is stimulated approximately 2-fold by inclusion of Ca2+ (1 mm) in the incubation medium. Spermidine efflux is stimulated approximately 10-fold in high [K+] (KD98) solution. In KD98 solution, efflux is strongly inhibited by divalent cations (Ki for Ba2+ block of spermidine efflux is approximately 0.1 mM), but not by tetraethylammonium ions or verapamil. Spermidine efflux rates were not different between control oocytes and those expressing HRK1 inward rectifier K+ (Kir) channels. When the membrane potential was clamped, either by changing external [K+] in oocytes expressing HRK1, or by 2-microelectrode voltage-clamp, spermidine efflux was shown to be strongly dependent on voltage, as expected for a simple electrodiffusive process, where spermidine3+ is the effluxing species. This result argues against spermidine diffusing out as an uncharged species, or in exchange for similarly charged counterions. These results are the first conclusive demonstration of a simple electrodiffusive pathway for spermidine efflux from cells.

Animals↗
PubMed1996

Saethre-Chotzen syndrome: a clinical, EEG and neuroradiological study.

Saethre-Chotzen syndrome is a form of acrocephalosyndactyly with autosomal dominant inheritance, characterized by craniosynostosis, facial asymmetry, palpebral ptosis, deviated nasal septum, partial cutaneous syndactyly, and various skeletal abnormalities. We studied in detail the neurological, EEG, and neuroradiological features of a group of 11 (6 male, 5 female) patients with Saethre-Chotzen syndrome. Four subjects were affected by seizures; they had paroxysmal EEG abnormalities, and gross neuroimaging revealed destructive brain lesions or malformations. Our findings suggest that CNS involvement in Saethre-Chotzen syndrome might be more severe than previously reported and support the wider use of neurophysiological and neuroimaging techniques in the study of children with this syndrome.

Acrocephalosyndactylia↗
PubMed1996

Electrophysiological findings in peripheral fibres of subjects with and without post-herpetic neuralgia.

The peripheral nervous system was studied using classical electrophysiological methods in 23 subjects with post-herpetic neuralgia (PHN), and compared with the same parameters in 64 herpes zoster (HZ) patients without PHN. The findings indicated sensory axonopathy, the severity of which varied in different patients. Ten percent of all cases showed segmental paresis corresponding to dermatomes affected by HZ. In another 17% of patients axonal motor damage was only detectable by EMG as denervation. No statistically significant difference was found between the two groups in the mean percentage differences of the electrophysiological data for peripheral sensory fibres with respect to mean control values, or between sides affected by HZ and healthy sides. Hence HZ is associated with sensory axonopathy, the severity of which is similar, on the whole, in the groups with and without PHN and stable in time. This suggests that damage to peripheral large-diameter sensory fibres is not the cause of PHN.

Age Distribution↗
PubMed1996

Exposure of astrocytes to thrombin reduces levels of the metabotropic glutamate receptor mGluR5.

Thrombin is one of the first regulatory molecules present at sites of CNS trauma or injury. Exposure of neuronal and glial cells to thrombin produces potent morphological as well as cytoprotective and cytotoxic effects, but little is known about how this important modulator affects neurotransmitter signaling. In astrocyte cultures that have been morphologically differentiated by exposure to transforming growth factor-alpha, addition of thrombin induced a retraction of astrocytic processes and suppressed the stimulation of phosphoinositide hydrolysis by the selective metabotropic glutamate receptor (mGluR) agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid. In addition to the suppression of phosphoinositide hydrolysis, thrombin treatment produced a corresponding reduction in level of mGluR5 mRNA as demonstrated with ribonuclease protection assay and reduced content of mGluR5 receptor protein as seen with western blotting. In contrast, thrombin exposure up-regulated astrocyte beta-actin mRNA levels. A synthetic hexapeptide with a sequence corresponding to the amino-terminus of the thrombin receptor's tethered ligand also mimicked the ability of thrombin to suppress mGluR5 levels and to increase beta-actin mRNA content, suggesting that these effects of thrombin are mediated by proteolytically activated cell surface thrombin receptors. Thrombin's suppressive effect on mGluR5 was resistant to pretreatment with pertussis toxin or various protein kinase and protein phosphatase inhibitors. However, the serine/threonine protein kinase inhibitor H-7 did prevent thrombin-induced reversal of astrocyte stellation and induction of beta-actin mRNA levels, indicating that these effects of thrombin involve a signaling pathway distinct from the one that mediates the suppressive effects of thrombin on mGluR5.

Animals↗
PubMed1996

Celiac disease in Down's syndrome with HLA serological and molecular studies.

The association between Down's syndrome (DS) and celiac disease (CD) has been confirmed by several authors. The sensitivity and specificity of antigliadin antibodies (AGAs), the clinical features of subjects with DS and CD (DS-CD+), the incidence of CD, and the results of serological and molecular class I and II HLA typing were determined in a sample of 57 Sicilian subjects with DS. Six (10.5%) and 17 subjects (29.8%) showed high levels of IgA AGAs and IgG AGAs, respectively. AGAs sensitivity and specificity were lower than in the population without DS. Ten people with DS were submitted to jejunal biopsy, and seven (12.2%) showed CD according to ESPGAN criteria. All seven patients were put on gluten-free diet, followed by rapid disappearance of symptoms. Class I and II HLA serological and molecular typing was carried out in seven DS-CD + subjects, 22 people with DS without CD (DS-CD-), five subjects with CD without DS, and 20 controls. Between DS-CD + and DS-CD- subjects, no statistically significant difference regarding serum HLA class I antigens was found. DQA1*0101 allele appears significantly in DS-CD + patients and deserves to be searched for in a larger sample to assess its meaning in the DS-CD association.

Adolescent↗
PubMed1996

Final height of patients who underwent bone marrow transplantation during childhood.

OBJECTIVE: To determine the impact on final adult height of bone marrow transplantation. METHODS: The final height of 28 long term survivors (18 males; 10 females), allografted before or at the onset of puberty, at a median age of 10.8 years (range 6.3 to 14.6) and who did not receive growth hormone (GH) treatment or other growth promoting agents, was evaluated. Median follow up period after bone marrow transplantation was 7.9 years (range 3.2 to 11.4), and age at the most recent evaluation 18.1 years (range 15.6 to 24.5). Height values were expressed in standard deviation score (SDS) from the mean of the normal population. Height at bone marrow transplantation was compared with final height as well as with parental genetic height. Patients were divided into three groups: severe aplastic anaemia (SAA): three patients given no radiotherapy; leukaemia-total body irradiation (TBI): 14 patients with acute or chronic leukaemia conditioned with chemotherapy and TBI; leukaemia-TBI with previous cranial radiation therapy (CRT): 11 patients. None of the patients had solid tumour. RESULTS: There was a decrease in final height SDS compared to pre-transplantation height SDS (paired t test, p < 0.0001). All patients except one reached an adult height above -2.0 SDS. A significant decrease in height SDS was found in the TBI and the CRT groups (paired t test, p = 0.02 and p = 0.0002, respectively). Whereas height SDS value at the time of transplant was higher than the genetic height SDS, final height SDS values were lower. CONCLUSIONS: Despite the decrease in height SDS found after bone marrow transplantation, 27 of the 28 patients spontaneously achieved what is considered to be a normal height SDS (above -2.0 SDS). This should be taken into account when considering GH treatment in children who underwent bone marrow transplantation for malignant haematological diseases.

Adolescent↗
PubMed1996

Effects of acyclovir on sensory axonal neuropathy, segmental motor paresis and postherpetic neuralgia in herpes zoster patients.

The effect of oral treatment with acyclovir (ACV) on sensory axonal neuropathy, segmental motor paresis and postherpetic neuralgia (PHN) was studied in 105 patients with herpes zoster. Forty-seven patients were treated with ACV at a dose of 4 g/day in 5 doses for at least a week; the others did not undergo any kind of treatment. Electrodiagnostic examination of the nerves and muscles corresponding to the dermatomeric lesions was performed, including sensory and motor nerve conduction studies, blink reflex and electromyography (EMG). The patients treated with ACV showed a significant reduction in the number of cases in which there was electrophysiological evidence of axonal damage in afferent fibres of nerves arising from roots corresponding to affected dermatomes. The treated group also showed a smaller incidence of segmental motor neuritis, clinically evident or only detectable by EMG as denervation. However, there was no significant difference between groups as far as the incidence of PHN was concerned. Oral treatment with ACV therefore reduces peripheral sensory axonopathy due to ganglion damage and prevents the possibility of spread to anterior roots and spinal motoneurones. In this way it reduces the incidence of segmental motor neuritis, but does not reduce the incidence of PHN.

Acyclovir↗
PubMed1996

Basal body temperature curves and endocrine pattern of menstrual cycles in Down syndrome.

We examined the basal body temperature curves and the endocrine pattern of 20 cycles from women with Down syndrome with regular menstrual cycles. Data were compared with those obtained from an age-matched population of healthy women with regular menses. Growth hormone deficiency was excluded for women with Down syndrome by pharmacological tests. Women with Down syndrome showed a significantly higher incidence of anovulation and luteal defects than controls (p < 0.001). Overall, and in ovulatory cycles, estradiol and progesterone plasma levels were greater in controls than in women with Down syndrome. No difference was observed for gonadotropin and androgen circulating levels between the two groups. It is concluded that in women with Down syndrome with regular menses, ovulatory events were less frequent and often characterized by luteal defects. This could be ascribed to an impairment of both follicular and luteal functions. However, reproduction is possible in such patients.

Adolescent↗
PubMed1996

Milia-like idiopathic calcinosis cutis: an unusual dermatosis associated with Down syndrome.

We describe two boys affected by Down syndrome (DS), who showed milia-like idiopathic calcinosis cutis (MICC). The clinical diagnosis was confirmed by histological examination. All reported cases are reviewed and compared. Syringeal structures play a significant part in the pathogenesis of this dermatosis. MICC appears to be a poorly recognized condition which, rarely, is associated with DS.

Calcinosis↗
PubMed1996

[Precancerous lesions of the penis].

Premalignant penile lesions have been associated to squamous cancer, although the true incidence of progression of these entities to squamous cell carcinoma is unknown. These lesions may coexist with or may antecede the occurrence of carcinoma. For this reason close follow-up of the patient is necessary to detect early evidence of malignant degeneration.

Humans↗
PubMed1996

[Conventional surgical treatment of penile tumors].

The surgical treatment of primary lesion in Carcinoma of the penis is the total excision of the carcinoma with tumor free margins. Distal preputial carcinomas without deep infiltration are often treated by extensive circumcision. Partial or total amputation of the penis is required by the location and the extent of the tumor. The evaluation and the treatment of the lymph nodes in penile cancer are still unclear.

Humans↗