Biomedical subjects

C Russo

Publications and source records attributed to C Russo.

At least 37 records · Page 2Linked to original sources

PubMed1999

Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors.

BACKGROUND: Intracranial primitive neuroectodermal tumors (PNETs) occur in the supratentorial and infratentorial regions of the brain. Although histologically similar, the natural history of the tumor at each site differs. The study goal was to determine whether there was evidence of a genetic difference between supratentorial and infratentorial PNETs. METHODS: Using comparative genomic hybridization (CGH), 53 PNETs were analyzed to determine copy number aberrations. Forty-three tumors were located in the cerebellum (IPNETs), and ten were supratentorial PNETs (SPNETs). All samples were reviewed to confirm the diagnosis. Each specimen had at least 50% tumor. RESULTS: Six of the 43 cases of IPNET had no copy number aberrations. In contrast, each case of SPNET had copy number aberrations detected by CGH. Statistically significant differences in copy number aberrations of chromosomes 14, 17, and 19 were detected in the two groups. The most common copy number aberration in the IPNETs was gain of chromosome 17q, which was observed in 16 of 43 cases (37%). However, no case of SPNET had gain of 17q. Loss of 14q was detected in four of ten SPNETs but was not detected in any of the IPNET cases. Loss of 19q was detected in 4 of 10 SPNETs and in only 1 of 43 IPNETs. CONCLUSIONS: These results indicate that the genetic aberrations of IPNETs differ from the genetic aberrations of SPNETs. Although they are similar histologically, SPNETs and IPNETs appear to be biologically distinct entities.

Adolescent↗

PubMed1999

Late radiation injury following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor.

PURPOSE: To document the late radiographic change following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor. METHODS AND MATERIALS: We reviewed long-term MRI scans on 21 patients with standard risk and high risk primitive neuroectodermal tumor treated with hyperfractionated radiotherapy following surgical resection. High risk patients also received adjuvant chemotherapy. Long-term scans were defined as scan obtained at least 1 year from diagnosis. Clinical follow-up data was available on all patients. RESULTS: Twelve of 21 patients had MRI evidence of necrosis, telangiectasia, white matter changes, basal ganglia change, or cerebral atrophy consistent with radiation injury. No patient required treatment for the radiographic change. CONCLUSIONS: Slightly over half of the patients had evidence of long-term radiation effect following craniospinal axis radiotherapy. However, no patient had frank clinical symptoms related to the radiographic findings.

Adolescent↗

PubMed1999

Postthymic development of CD28-CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype.

During human aging, one of the major changes in the T cell repertoire is a dramatic expansion of T cells with the atypical CD28-CD8+ phenotype. In this study, we show that this increase is a consequence not only of an expansion in the CD28-CD8+ population but also of a decrease in the number of CD28+CD8+ T cells. The decrease in circulating CD28+CD8+ T cells is dramatically accelerated after the age of 50 and is not accompanied by an equivalent reduction in the CD28+CD8+ subset. Our findings confirm that aging leads to an accumulation of CD45RO+ T cells within the CD28+CD8+ subset as previously observed. Surprisingly, we found an increase in CD45RA+ expression with age in the CD28-CD8+ subset. Immune-phenotyping for activation markers, measurement of telomere DNA content, and cytokine production analysis indicate that the large majority of CD28-CD8+ T cells are Ag-experienced, despite their CD45RA+ phenotype. Our study further demonstrates that the poor proliferative response displayed by CD28-CD8+ T cells is not a consequence of telomere shortening. Also, analysis of cytokine production at the single cell level revealed that the proportions of IFN-gamma +, IL-4+, and IL-10+ T cells are considerably higher among the CD28-CD8+ than the CD28+CD8+ subset. In summary, these data explain the presence of CD45RA+ T cells in the elderly, shed light on the phylogenetic origin of CD28-CD8+ T cells, and suggest a role for these cells in the immune senescence process.

Adolescent↗

PubMed1999

Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: results of a Phase II study.

PURPOSE: To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas. METHODS AND MATERIALS: Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse. RESULTS: A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site. CONCLUSIONS: Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain.

Adolescent↗

PubMed1999

Complete remission of refractory anemia following a single high dose of cyclophosphamide.

We describe a case of stable complete remission in a patient with refractory anemia complicated by severe autoimmune hemolytic anemia, achieved with a single high dose (4 g/m2) of cyclophosphamide (cyclo). Concomitantly, an effective mobilization of CD34-positive cells was induced. Other immunosuppressive approaches including high-dose methylprednisolone, high-dose immunoglobulin, and cyclosporine had been ineffective. This finding suggests that, in selected cases, an immunologic mechanism may mediate cytopenia in myelodysplastic syndromes (MDS). In addition, it demonstrates that successful mobilization of peripheral blood stem cells can be induced with high-dose cyclo in MDS.

Adult↗

PubMed1999

Complete remission in acute myeloid leukaemia with t(8;21) following treatment with G-CSF: flow cytometric analysis of in vivo and in vitro effects on cell maturation.

A 75-year-old patient diagnosed as having acute myeloid leukaemia with t(8;21) received G-CSF alone as induction therapy. Complete remission was achieved following 2 weeks of treatment. Flow cytometric analysis, performed by CD45 technique modified by the introduction of preliminary gating with LDS-751, confirmed the disappearance of blast cells along with myeloid maturation. Finally, in vitro studies demonstrated that G-CSF, as compared to other differentiation inducers, was able to induce a striking effect toward neutrophilic differentiation.

Acute Disease↗

PubMed1999

Emotion-induced myoclonic absence-like seizures in a patient with inv-dup(15) syndrome: a clinical, EEG, and molecular genetic study.

We have described a clinical EEG and molecular genetic study of a 9-year-old boy with inv-dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5-20 s after the onset of repeated cheek-kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence-like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11-q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral gamma-aminobutyric acid (GABA)-mediated inhibition accounts for the severe epilepsy that we observed in this patient.

Child↗

PubMed1999

Idiopathic generalized epilepsies with versive or circling seizures.

OBJECTIVES: To describe the electroclinical features of the idiopathic generalized epilepsies (IGEs) with versive or circling seizures. METHODS: Sixteen patients with versive or circling seizures and interictal electroclinical features of IGE were studied. Patients with insufficient clinical or imaging data, with a follow-up period less than 1 year or with partial seizures in addition to the versive or circling ones were excluded from the study. All patients underwent full interictal clinical and neurophysiological studies. The EEG patterns of 13 versive or circling seizures from 4 patients were also analyzed. RESULTS: A specific IGE syndrome was recognized in 9 out of the 16 patients (56%). More specific, 1 patient had childhood absence epilepsy (CAE), 4 had juvenile absence epilepsy (JAE), and 4 had juvenile myoclonic epilepsy (JME). No specific IGE syndrome was recognizable in the remaining 7 patients (44%). These 7 patients had a juvenile epileptic syndrome (mean age at onset of seizures was 15.7 years) characterized by versive or circling seizures followed or not by generalized tonic-clonic fits. Three main EEG patterns were identified during versive or circling seizures: 1) generalized spike-and-wave discharges at 3-4 cps; 2) generalized polyspike-and-wave discharges at 1 to 2.5 cps beginning with generalized fast activity at 12-14 cps, and 3) generalized spike-and-wave discharges at 3-4 cps intermingled with fast activity at 12-14 cps. Most patients had good response to treatment on a single drug regimen (mainly valproic acid). CONCLUSIONS: Versive or circling seizures may occur in the context of an IGE. Although many individuals share the features of different IGE syndromes including CAE, JAE and JME, a consistent number of patients, who show circling or versive seizures solely, remain without a specific syndromic diagnosis. When occurring in the context of IGE, circling or versive seizures do not worsen the prognosis.

Adolescent↗

PubMed1999

Genetic polymorphisms of the renin-angiotensin system and atheromatous renal artery stenosis.

Genes that influence the renin-angiotensin system have been investigated in recent years as potential etiologic candidates of cardiovascular and renal diseases. In atheromatous renal artery stenosis (RAS), a condition characterized by persistent activation of the renin-angiotensin system, the study of these genes may be of particular relevance. We evaluated angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, and angiotensin II receptor (ATR) A1166C polymorphisms in relation to the occurrence of RAS. We studied 58 patients with angiographically documented RAS; 102 normotensive subjects with normal coronary arteries and no history or clinical or instrumental evidence of atherosclerosis in other vascular districts were considered the control group. Patients had a significantly higher D allele frequency (0.70 versus 0.55; chi(2) 6.88, P=0.01; odds ratio [OR] 1. 9, 95% CI 1.17 to 3.07) than did the control population; 48.3% of patients were homozygous for DD (chi(2) 6.62, P<0.05; OR 2.04, 95% CI 1.05 to 3.95); and only 8.6% carried the II genotype (OR 0.34, 95% CI 0.19 to 1.47). No significant association was found for AGT M235T and ATR A1166C. Our results suggest a predisposing role for ACE genetic polymorphism in the development and progression of atheromatous RAS.

Adult↗

PubMed1999

Resistance to several steroids in two sisters.

A 14-yr-old native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of apparent mineralocorticoid excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens, but no resistance to vitamin D or thyroid hormones. She lacked Cushingoid features despite significantly high cortisol levels. Menstruation was regular, and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly due to a coactivator defect.

Adolescent↗

PubMed1999

[Maternal-fetal transmission of HCV. Role of HIV as a risk factor].

BACKGROUND: The aim of this study is to determine the rate of vertical transmission of hepatitis C and to analyse the concomitant infection by HIV as a risk factor. METHODS: We have studied the perinatal transmission of HCV in 22 pregnancies: 14 in women HCV+/HIV-, 8 in women HCV+/HIV+. We have performed the following tests on sera: test RIBA II to search for Ab anti-HCV, alanine transaminase (ALT) evaluation and HCV-RNA research by PCR. These tests were performed on sera from infants at birth and, then, during one year every three months. RESULTS: Within one year Ab anti-HCV disappeared in 20 of 22 pregnancies: two infants positive by Ab anti-HCV were born to HIV+ mothers and they were the only two who showed abnormal ALT values and detectable levels of HCV-RNA. Finally 10 of 14 infants born to HCV+/HIV- mothers were breast-fed and none was infected. CONCLUSIONS: We conclude that HCV mother-to-child transmission is an uncommon event, breast-milking is safety, and the concomitant infection by HIV could represent a risk factor for vertical transmission of hepatitis C.

Female↗

PubMed1998

Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease.

We have characterized the interaction between apolipoprotein E (apoE) and amyloid beta peptide (Abeta) in the soluble fraction of the cerebral cortex of Alzheimer's disease (AD) and control subjects. Western blot analysis with specific antibodies identified in both groups a complex composed of the full-length apoE and Abeta peptides ending at residues 40 and 42. The apoE-Abeta soluble aggregate is less stable in AD brains than in controls, when treated with the anionic detergent SDS. The complex is present in significantly higher quantity in control than in AD brains, whereas in the insoluble fraction an inverse correlation has previously been reported. Moreover, in the AD subjects the Abeta bound to apoE is more sensitive to protease digestion than is the unbound Abeta. Taken together, our results indicate that in normal brains apoE efficiently binds and sequesters Abeta, preventing its aggregation. In AD, the impaired apoE-Abeta binding leads to the critical accumulation of Abeta, facilitating plaque formation.

Alzheimer Disease↗

PubMed1998

Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and folate in subjects from northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic-environmental interaction.

Moderate elevation of plasma total homocysteine (tHcy) is a strong and independent risk factor for coronary artery disease (CAD). It can result from genetic or nutrient-related disturbances in the transsulfuration or remethylation pathways for Hcy metabolism. A point mutation (C677T; Ala-to-Val) in the gene encoding the 5, 10-methylenetetrahydrofolate reductase (MTHFR) has been recently reported to render the enzyme thermolabile and less active. Studies on the role of this mutation as a risk factor for CAD have given conflicting results. We studied a total of 415 subjects, 278 with angiographically documented multivessel CAD and 137 with angiographically documented normal coronary arteries. The overall frequency of the MTHFR V/V homozygous genotype was 15.7% (with 52.5% heterozygous and 31.8% normal). Subgroup analysis showed no significant differences between CAD and CAD-free subjects. A genotype/phenotype correlation study showed a marked effect of folate on the association between MTHFR genotypes and tHcy. Among individuals with folate levels below the median (11.5 nmol/L), fasting tHcy was significantly increased not only in V/V homozygotes (by 59%) but also, at intermediate values, in A/V heterozygotes (by 21% on average). Conversely, the mutation resulted neutral with respect to tHcy levels in subjects with adequate folate levels. We conclude that, in our population, the MTHFR C677T mutation is rather common, but it does not appear to be associated per se to CAD. A genetic-environmental interaction may contribute to the vascular risk by elevating tHcy when folate status is low.

Adult↗

PubMed1998

A novel one-step, highly sensitive fluorometric assay to evaluate cell-mediated cytotoxicity.

In this study, a fluorometric method using alamarBlue has been developed for detecting cell-mediated cytotoxicity in vitro. AlamarBlue is a non-toxic metabolic indicator of viable cells that becomes fluorescent upon mitochondrial reduction. Specific lysis of targets by effector cells is quantified by comparing the total number of viable cells in wells containing effector and targets together, with wells where target and effector cells were separately seeded. Cell-mediated cytotoxic activity by alloreactive T cells and natural killer cells has been detected using a novel application of the alamarBlue technique. The assay that we have developed to detect cell-mediated cytotoxicity is extremely sensitive and specific and requires a significant lower number of effector cells than the standard 51Cr assay. Since alamarBlue reagent is non-toxic to cells and the assay can be performed under sterile conditions, effector cells may be recovered at the end for further analysis or cell expansion, if desired. Direct comparison of cell-mediated cytotoxicity measured by the alamarBlue method with the standard 51Cr release assay revealed that the former method is as specific and more sensitive than the conventional assay. Moreover, very small inter and intra-assay variations have been observed for alamarBlue cytotoxicity assays. In conclusion, this study shows that the alamarBlue assay is an extremely sensitive, economical, simple and non-toxic procedure to evaluate cell-mediated cytotoxicity that yields accurate results using a limited number of effector cells. Furthermore, since this assay is a one-step procedure, and does not involve any risk for the personnel, it may be useful to analyze automatically cell-mediated cytotoxicity in a large number of samples.

Animals↗

PubMed1998

Organizational effects of estrogens on brain vasotocin and sexual behavior in quail.

Reproductive behavior is sexually differentiated in quail: The male-typical copulatory behavior is never observed in females even after treatment with high doses of testosterone (T). This sex difference in behavioral responsiveness to T is organized during the embryonic period by the exposure of female embryo to estrogens. We showed recently that the sexually dimorphic medial preoptic nucleus (POM), a structure that plays a key role in the activation of male copulatory behavior, is innervated by a dense steroid-sensitive network of vasotocin-immunoreactive (VT-ir) fibers in male quail This innervation is almost completely absent in the female POM and is not induced by a chronic treatment with T, suggesting that this neurochemical difference could be organizational in nature. This idea was tested by injecting fertilized quail eggs of both sexes on day 9 of incubation with either estradiol benzoate (EB) (25 microg, a treatment that suppresses the capacity to show copulatory behavior in adulthood) or the aromatase inhibitor R76713 (10 microg, a treatment that makes adult females behaviorally responsive to T), or with the solvents as a control (C). At 3 weeks posthatch, all subjects were gonadectomized and later implanted with Silastic capsules filled with T. Two weeks later, all birds were perfused and brain sections were processed for VT immunocytochemistry. Despite the similarity of the adult endocrine conditions of the subjects (all were gonadectomized and treated with T Silastic implants providing the same plasma level of steroid to all subjects), major qualitative differences were observed in the density of VT-ir structures in the POM of the different groups. Dense immunoreactive structures (fibers and a few cells) were observed in the POM of C males but not females; EB males had completely lost this immunoreactivity (and lost the capacity to display copulatory behavior); and, conversely, R76713 females displayed a male-typical VT-ir system in the nucleus (and also high levels of copulatory behavior). Similar changes in immunoreactivity were seen in the nucleus of the stria terminalis and in the lateral septum (VT-ir fibers only in this case) but not in the magnocellular vasotocinergic system. These neurochemical changes closely parallel the effects of the embryonic treatments on male copulatory behavior. The vasotocinergic system of the POM can therefore be considered an accurate marker of the sexual differentiation of brain circuits mediating this behavior.

Analysis of Variance↗

PubMed1998

Genomic and non-genomic mechanisms of oxytocin receptor regulation.

Our recent studies have shown that regulation of uterine oxytocin (OT) binding involves at least two different mechanism: Estradiol (E2)-induced upregulation is accompanied by an increase in OT receptor (OTR) mRNA accumulation, implying that the E2 effect is mediated via increased OTR gene transcription and/or OTR mRNA stabilization. In contrast, P (P)-induced OTR down-regulation occurs via a novel non-genomic mechanism, involving a direct interaction of P with the OTR at the level of the cell membrane. We found that P specifically binds to the OTR and inhibits its ligand binding and signalling functions. Physiological levels of P repress in vitro the ligand binding capacity (Bmax) of the OTR by > 50%. When expressed in CHO cells, the OTR provides a high affinity (Kd: 20nM) membrane binding site for P. OT-induced inositol phosphate production and intracellular calcium mobilization is inhibited 85% and 90%, respectively, by P. These effects are specific as signalling and binding functions of the closely related V1a vasopressin receptor remain unaffected by P, and as other, related steroids are devoid of any effect on OTR binding or signalling functions. The present observation of a specific interaction of a steroid with a G-protein-linked receptor defines a new mechanism of non-genomic steroid action and uncovers a novel level of crosstalk between steroid and peptide hormone action.

Animals↗

PubMed1998

Usefulness of latero-orbital electrodes in detecting interictal epileptiform activity--a study of 60 patients with complex partial seizures.

OBJECTIVES: The use of latero-orbital (Lo) electrodes is a routine practice in any EEG laboratory to evaluate eye motion, but there are no data about their usefulness in revealing interictal epileptiform abnormalities. METHODS: In 60 consecutive patients (27 men, 33 women, mean age 36.8 years, range 17-72) with complex partial seizures, we prospectively evaluated the utility of Lo electrodes in comparison with anterior temporal (AT) electrodes, for the detection of interictal epileptiform discharges (SW). RESULTS: No epileptiform abnormality was seen in 4/60 patients. Both AT and Lo electrodes were significantly superior to 10-20 electrodes for detection of both patients and foci. Indeed, the standard 10-20 system alone allowed the detection of only 39 independent epileptiform foci in 35/56 (63%) patients, while AT and Lo electrodes were necessary for detection of 23 epileptiform foci in the remaining 21/56 (37%) patients. Importantly, there was no statistically significant difference in detection between AT and Lo electrodes. CONCLUSIONS: Recordings from Lo electrodes are comparable to those from AT electrodes and are useful for localizing interictal temporal spiking activity. Lo electrodes may be substituted for basal electrodes in the day-to-day evaluation of patients with complex partial seizures.

Adolescent↗

PubMed1998

Chemiluminescence imaging in bioanalysis.

The development, analytical performance and applications of chemiluminescence imaging as a tool for quantitative analyte localization in target biological specimens are described. The detection of acetylcholinesterase activity both in array format and on a target surface are described. A proposed application of the method is a 384 well microtiter format assay for high throughput screening of acetylcholinesterase inhibitors such as tacrine, a drug widely used in the treatment of Alzheimer's disease, and two recently developed analogues. The chemiluminescent system in conjunction with optical microscopy allowed localization of acetylcholinesterase in brain tissue sections. We also describe the chemiluminescent immunohistochemical localization of interleukin 8 in Helicobacter pylori infected gastric mucosa cryosections and an in situ hybridization assay for the detection of herpes simplex virus DNA in single cells.

Acetylcholinesterase↗