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1.
Early Hum Dev ; 134: 14-18, 2019 07.
Article in English | MEDLINE | ID: mdl-31112857

ABSTRACT

BACKGROUND: The association between cardiorespiratory events (CRE) and gastro-esophageal reflux (GER) among neonates is still controversial. AIMS: To test such an association in preterm and term infants. STUDY DESIGN: Prospective observational study. SUBJECTS: Forty-seven infants with suspected GER and recurrent CRE admitted at a neonatal intensive care unit, who underwent simultaneous and synchronized 24-hour recording of heart rate (HR), peripheral oxygen saturation (SpO2) and pH-impedance monitoring (MII-pH). HR/SpO2 data were filtered to avoid artefactual episodes of hypoxia and hypoperfusion. OUTCOME MEASURES: The main outcome measure was the symptom association probability (SAP), with a 2-minute time window. Infants with positive (>95%) and negative (≤95%) SAP index tests were compared by univariate and multivariate statistics. RESULTS: Median gestational age at birth was 294/7 weeks, median age at study 36 days. We recorded 3341 GER events and 4936 CRE (4710 desaturations, 226 bradycardias); 609/4936 (12%) CRE were temporally associated with GER episodes: 338 preceded and 271 followed GER events. The SAP index was significant in 5/47 (11%) patients. The SAP index including only CRE following GER events was significant in 3/47 (6%). There was no significant difference in the number of acid, weakly acid, non-acid, pH-only events preceding or following CRE between infants with SAP-positive and SAP-negative tests. Infants with positive SAP-index tests compared to those with SAP-negative tests had lower weight gain in the three days preceding the test and tended to have lower birth weight. CONCLUSIONS: GER and CRE were associated in <11% of patients. The evaluation of ponderal growth might be helpful in predicting such an association.


Subject(s)
Apnea/epidemiology , Bradycardia/epidemiology , Gastroesophageal Reflux/epidemiology , Infant, Premature/physiology , Female , Heart Rate , Humans , Infant, Newborn , Male , Oxygen Consumption
2.
Clin Ter ; 168(5): e297-e299, 2017.
Article in English | MEDLINE | ID: mdl-29044351

ABSTRACT

Survival of preterm infants have dramatically improved over the last decades. Nonetheless, infants born preterm remain vulnerable to many complications, including necrotizing enterocolitis (NEC). The severity of the disease and the mortality rate are directly correlated with decreasing gestational age and birth weight. Despite surgical treatment mortality rate remains very high in extremely premature infants, especially in newborns at the lowest limit of viability. Survival of infants of birth weight (BW) below 750 g has been increasingly reported in recent years, however the overall mortality in extremely low "BW" infants (ELBW) requiring surgery for NEC has not decreased over the past years. We describe our experience with a male preterm infant who survived after an ileostomy procedure for Bell stage II NEC, with improving neuromotor skills at 2 years follow up. Although standard indication to surgery is Bell stage III, in our case the choice of minimal laparotomy, exploration of the bowel and ileostomy at Bell stage II was safe and effective. Our experience suggest that surgery has not a negative impact on survival and ileostomy could prevent further damage of the bowel in NEC. We hypothesize that indication to surgery at an earlier stage may prevent further progression of the disease without a significantly negative impact on survival. Further studies are needed to confirm the appropriateness of this approach in ELBW infants.


Subject(s)
Enterocolitis, Necrotizing/surgery , Ileostomy , Infant, Low Birth Weight , Infant, Premature, Diseases/surgery , Infant, Premature , Humans , Infant , Infant, Newborn , Laparotomy , Male
3.
Curr Genomics ; 17(1): 70-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-27013925

ABSTRACT

Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder to the upper urinary tract. It is the most common congenital urological anomaly affecting 1-2% of children and 30-40% of patients with urinary tract infections. VUR is a major risk factor for pyelonephritic scarring and chronic renal failure in children. It is the result of a shortened intravesical ureter with an enlarged or malpositioned ureteric orifice. An ectopic embryonal ureteric budding development is implicated in the pathogenesis of VUR, which is a complex genetic developmental disorder. Many genes are involved in the ureteric budding formation and subsequently in the urinary tract and kidney development. Previous studies demonstrate an heterogeneous genetic pattern of VUR. In fact no single major locus or gene for primary VUR has been identified. It is likely that different forms of VUR with different genetic determinantes are present. Moreover genetic studies of syndromes with associated VUR have revealed several possible candidate genes involved in the pathogenesis of VUR and related urinary tract malformations. Mutations in genes essential for urinary tract morphogenesis are linked to numerous congenital syndromes, and in most of those VUR is a feature. The Authors provide an overview of the developmental processes leading to the VUR. The different genes and signaling pathways controlling the embryonal urinary tract development are analyzed. A better understanding of VUR genetic bases could improve the management of this condition in children.

4.
Minerva Pediatr ; 66(4): 287-91, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25198565

ABSTRACT

AIM: Aim of the study was to compare multichannel intraluminal impedance (MII)-pH monitoring versus pH only, as first-line assessment of gastroesophageal reflux (GER) in children and to define the relation between GER and symptoms as well relation between types of GER and age of children. METHODS: All the patients with GER were divided in three groups: A, younger than 24 months, B, older than 24 months with typical symptoms and C, older than 24 months with atypical symptoms. The groups A and C underwent a combined MII-pH recording. The group B underwent a only pH recording. MII-pH measurements were performed in 89 children (63 group A and 26 group C), only pH measurements in 170 cases (group B). RESULTS: Sixty-seven of the 247 pH measurements demonstrated abnormal reflux indices: 25.0% (group A), 28.8% (group B) and 20.8% (group C). The number of the reflux periods and the total reflux index were highest in the patients of the group B, but the number of long reflux periods was highest in the group C. Abnormal values at MII results were found in 36 cases: 41.7% in group A (high number of weakly acid refluxes events) and 45.8% in group C (similar number of acid and weakly acid events). The MII were considered pathological because of high number of reflux episodes and symptom index ≥ 50% respectively in 60.0% and 40.0% of the group A and 27.3% and 62.7% of the group C. CONCLUSION: MII-pH study must be reserved to patients younger than 2-year old (high probability of weakly acid reflux) and children with atypical symptoms.


Subject(s)
Electric Impedance , Esophageal pH Monitoring , Gastroesophageal Reflux/diagnosis , Hydrogen-Ion Concentration , Adolescent , Child , Child, Preschool , Female , Gastroesophageal Reflux/physiopathology , Humans , Infant , Male , Prognosis , Retrospective Studies , Time Factors
5.
Minerva Pediatr ; 65(2): 193-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23612265

ABSTRACT

AIM: Constipation is a common pediatric problem. Sometimes the hospitalization is necessary and in these patients the organic cause should be verified. The authors report their experience in the management of children with severe constipation. METHODS: Anorectal manometry (ARM) was performed after a careful examination of perineum and bowel disimpaction. Once organic cause had be excluded, the patient got medical therapy. If recto-anal inhibitory reflex (RAIR) was absent, not collaborative patient or medical treatment failed, the child underwent contrast enema (CE) and rectal suction biopsies (RSB). Local anesthetics were used for anal fissures or internal anal sphincter (IAS) hypertonia. Anal malformations and Hirschsprung's disease (HD) were surgically treated. Posterior sagittal anorectoplasty was performed for anal malformations. RESULTS: In 5 years 98 children (63 males) were observed (mean age 6 years). 5 children were premature for gestational age, 4 presented failure to thrive, 5 anal malformations and 45 anal fissures. ARM was performed in 87 children and 74 of them showed normal RAIR. Hypertonia of the IAS was recorded in 38 patients. RAIR was absent/unclear in 13 patients. Follow-up revealed 6 patients (negative to ARM) with poor results without oral laxative. CE was performed in 19 children (2 positive cases) and RBS in 25 patients (2 cases of HD). CONCLUSION: Children with severe constipation must be carefully observed and studied because of not negligible incidence of organic cause. The first step in the management of these patients is the evacuation of the fecaloma.


Subject(s)
Constipation/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies , Severity of Illness Index
6.
Pediatr Med Chir ; 33(3): 134-6, 2011.
Article in English | MEDLINE | ID: mdl-22145297

ABSTRACT

Posterior urethral hemangioma (PUH) is a rare congenital lesion, included in group of polypoid or papillary lesion of the prostatic urethra. This lesion is responsible for a variety of symptoms in children that may be associated or isolated, sometimes its finding is occasional. The diagnosis is usually made by ultrasonography and cystourethrogram, but the gold standard is represented by the urethrocystoscopy with double possibility: diagnostic and therapeutic. The Authors report a case of 1-year-old boy with persisting haematuria, in whom a previews cystoscopy didn't find any cause of haematuria. An accurate urethrocystoscopy let to make diagnosis of prostatic urethral polyp, a transurethral resection was performed and pathological assessment confirmed the diagnosis of PUH.


Subject(s)
Hematuria/etiology , Polyps/complications , Urethral Diseases/complications , Humans , Infant , Male
7.
Minerva Pediatr ; 63(3): 163-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21654596

ABSTRACT

AIM: Recently laparoscopic endorectal pull-through (LERPT) has been widely performed for treatment of Hirschsprung's disease (HD) as a one stage procedure. In long segment aganglionosis (LSA) and in case of total colonic aganglionosis (TCA) a staged procedure can be preferred. The authors report their experience in the staged LERPT for LSA and TCA. METHODS: In the last five years we treated 4 infants (3 male, 1 female) with LSA and TCA. The mean age at presentation was 40 days (2-110 days). In 3 patients we performed in the first step rectal biopsies, multiple laparoscopic biopsies and stoma. In one case ­ presenting as small bowel obstruction - we performed an emergency laparotomy for ileostomy and biopsies of the bowel. Histology showed 2 left colon aganglionosis (LCA) and 2 TCA. The LERPT was performed at a main age of 10 months. After stoma closure the LERPT was performed according to Georgeson's technique. RESULTS: There were no intraoperative complications. The patient with previous laparotomy needed conversion because of the abdominal adhesions. The two infants with LCA had preoperative and recurrent postoperative enterocolitis. In one case a successful posterior anorectal myectomy was performed. At follow up the children present constipation. The patient with TCA undergoing to LERPT presents a good frequency of defecation. CONCLUSION: Our experience, although on limited series, shows that staged minimally invasive surgical treatment can be safely performed in the LSA and TCA, but conversion can be necessary especially in case of previous laparotomy.


Subject(s)
Hirschsprung Disease/surgery , Laparoscopy/methods , Digestive System Surgical Procedures/methods , Female , Humans , Infant , Infant, Newborn , Male , Rectum
8.
J Pediatr Urol ; 6(6): 550-4, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20106723

ABSTRACT

OBJECT: To retrospectively review the value of laparoscopy in the management of impalpable testis. MATERIALS AND METHODS: In 1993-2006, 182 laparoscopies for impalpable testis were performed for a total of 194 testicular units. Five laparoscopic findings were considered: testicular ectopia, intra-abdominal testis, and cord structures that are blind ending, completely absent (agenesis) or entering the internal inguinal ring. RESULTS: In 62 cases an intra-abdominal testis was found; 18 were classified as high and managed by a laparoscopic Fowler-Stephens procedure. Cord structures entering the inguinal ring were observed in 77 patients and 45 underwent an inguinal exploration: a testis was found in 12 cases and in 33 a remnant was excised. In 35 cases, intra-abdominal blind ending vas and vessels were observed and eight showed testicular agenesis. No major surgical complications were recorded. Follow up ranged from 1 to 3 years. CONCLUSIONS: Our study confirms the value of laparoscopy in the management of non-palpable testis, providing a definitive diagnosis by the direct view of spermatic bundle and testis. Ninety-three patients were managed by laparoscopy only, and in 44 it was essential for the subsequent surgical approach. When the internal inguinal ring is patent and/or normal spermatic vessels are present an inguinal exploration is mandatory.


Subject(s)
Cryptorchidism/surgery , Laparoscopy , Child , Child, Preschool , Cryptorchidism/diagnosis , Cryptorchidism/pathology , Humans , Infant , Laparoscopy/methods , Male
9.
Colorectal Dis ; 12(10): 1044-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19604284

ABSTRACT

AIM: The aim of this study was to evaluate the effectiveness of a differential diagnostic approach to Hirshchsprung's Disease (HD) on the basis of age. METHOD: Data on 185 consecutive children with suspected HD were subjected to an age-related diagnostic approach. The patients were divided into two groups according to age (A < 1 year; B > 1 year). Children in Group A had rectal suction biopsy (RSB) and contrast enema (CE), and in Group B anorectal manometry (ARM) was performed. Patients with a normal recto-anal inhibitory reflex (RAIR) underwent bowel disimpaction and medical treatment. Only selected cases in Group B underwent RSB and CE. RESULTS: In Group A (18 patients) CE showed a colonic transitional zone in three patients, whereas RSB led to the diagnosis of HD in nine. In Group B (167 patients) ARM was not possible in seven patients and it was normal in 140 (normal anal sphincter pressure: 83; hypertonia of the internal anal sphincter: 57). The RAIR was negative in 20 patients. RSB performed in 31 children in Group B confirmed HD in three patients. CONCLUSIONS: For patients with a neonatal onset of constipation RSB is the best diagnostic technique. Chronic constipation is rarely due to HD and ARM is a useful non-invasive screening tool.


Subject(s)
Hirschsprung Disease/diagnosis , Age Factors , Child, Preschool , Diagnosis, Differential , Female , Hirschsprung Disease/pathology , Hirschsprung Disease/surgery , Humans , Infant , Laparoscopy , Male
10.
Colorectal Dis ; 11(5): 480-4, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18662235

ABSTRACT

OBJECTIVE: Constipation is one of the most frequent disorders of the digestive tract in children and it can be an important problem in paediatric and surgical practice. Most of the time, the cause is psychological or because of a slowing of colonic transit, but it can be a sign of organic gastrointestinal outlet obstruction. Some patients with chronic constipation are resistant to a medical approach and they present with a severe form of constipation that needs recurrent hospital admission. Anorectal manometry (ARM) is a noninvasive procedure and it helps to explain the mechanisms of defecation disorders. The aim of the present study was to evaluate the role of ARM in children with severe constipation. METHOD: From October 2003 to October 2006, in the Paediatric Surgery Unit, 85 children - aged more than 1 year - with severe constipation were seen. The mean age was 5 years (range, 1-13). At presentation, every child had abdominal and rectal examination in order to identify abdominal distension or faecal masses. Bowel preparation with enemas was performed before ARM in patient with a rectal faecaloma. Myoelectric activity of the internal anal sphincter and resting anal tone was recorded; recto-anal inhibitory reflex (RAIR) was tested to exclude Hirschsprung's disease (HD). Anal tone was considered normal until 50 cm H(2)O. When the RAIR was absent, the patient underwent rectal suction biopsies (RSB) for histology and acetylcholinesterase histochemistry. In cases of normal or high anal tone with the RAIR present, the child had bowel cleaning, medical treatment, 2- and 6-month follow-up. Children with ineffective treatment at follow-up underwent RSB. In case of HD, a laparoscopic-assisted endorectal pull-through (ERPT) according to Georgeson's technique was performed. RESULTS: Seventy per cent of the patients had bowel preparation before ARM. In four patients the ARM was impossible to assess because of crying. In 28 patients, the anal tone result was higher than 50 cm H(2)O and local treatment with anaesthetic agents was used for 8 weeks. Seventeen patients underwent RSB: 11 patients with RAIR absent/unclear, 4 noncooperative children and 2 patients with ineffective medical treatment at follow-up. HD was diagnosed in 2 patients and laparoscopic-assisted ERPT was performed. The remaining patients had good results at 6-month follow-up. CONCLUSION: ARM is a noninvasive diagnostic tool to study the mechanism of defecation in children with constipation in order to prescribe the appropriate treatment. This procedure can be used in every child - aged more than 1 year - with severe constipation and assessment of the RAIR can select the cases for RSB.


Subject(s)
Constipation/physiopathology , Manometry/methods , Adolescent , Anal Canal/physiopathology , Biopsy/methods , Child , Child, Preschool , Constipation/therapy , Defecation/physiology , Female , Humans , Infant , Male , Rectum/pathology
11.
Minerva Pediatr ; 59(2): 157-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17404566

ABSTRACT

Neonatal adrenal hemorrhage may rarely present as scrotal hematoma. This condition can simulate a torsion of the testis requiring an immediate surgical exploration of the scrotum. Ultrasonographic study of the abdomen can find out intraperitoneal or retroperitoneal bleeding in order to avoid unnecessary surgical intervention. The case of a newborn with right adrenal hemorrhage presenting as left scrotal hematoma is reported.


Subject(s)
Adrenal Gland Diseases/complications , Genital Diseases, Male/etiology , Hematoma/etiology , Hemorrhage/complications , Scrotum , Adrenal Gland Diseases/diagnosis , Hemorrhage/diagnosis , Humans , Infant, Newborn , Male
12.
J Virol ; 81(9): 4776-86, 2007 May.
Article in English | MEDLINE | ID: mdl-17329339

ABSTRACT

Viruses encounter changing selective pressures during transmission between hosts, including host-specific immune responses and potentially varying functional demands on specific proteins. The human immunodeficiency virus type 1 Nef protein performs several functions potentially important for successful infection, including immune escape via down-regulation of class I major histocompatibility complex (MHC-I) and direct enhancement of viral infectivity and replication. Nef is also a major target of the host cytotoxic T-lymphocyte (CTL) response. To examine the impact of changing selective pressures on Nef functions following sexual transmission, we analyzed genetic and functional changes in nef clones from six transmission events. Phylogenetic analyses indicated that the diversity of nef was similar in both sources and acutely infected recipients, the patterns of selection across transmission were variable, and regions of Nef associated with distinct functions evolved similarly in sources and recipients. These results weighed against the selection of specific Nef functions by transmission or during acute infection. Measurement of Nef function provided no evidence that the down-regulation of either CD4 or MHC-I was optimized by transmission or during acute infection, although rare nef clones from sources that were impaired in these activities were not detected in recipients. Nef-specific CTL activity was detected as early as 3 weeks after infection and appeared to be an evolutionary force driving the diversification of nef. Despite the change in selective pressure between the source and recipient immune systems and concomitant genetic diversity, the majority of Nef proteins maintained robust abilities to down-regulate MHC-I and CD4. These data suggest that both functions are important for the successful establishment of infection in a new host.


Subject(s)
Evolution, Molecular , Gene Expression Regulation, Viral , Gene Products, nef/genetics , Gene Products, nef/metabolism , Genetic Variation , HIV Infections/transmission , HIV-1/genetics , Selection, Genetic , Amino Acid Sequence , Base Sequence , Blotting, Western , CD4 Antigens/metabolism , Flow Cytometry , Genes, MHC Class I/physiology , HIV Infections/metabolism , Humans , Likelihood Functions , Models, Genetic , Molecular Sequence Data , Phylogeny , Sequence Alignment , Sequence Analysis, DNA , T-Lymphocytes, Cytotoxic/immunology , nef Gene Products, Human Immunodeficiency Virus
13.
Minerva Pediatr ; 57(1): 35-40, 2005 Feb.
Article in Italian | MEDLINE | ID: mdl-15791200

ABSTRACT

AIM: To verify the efficacy of botulinus toxin A (TB-A) in treating children with neuropathic bladder secondary to myelomeningocele (MMC) with detrusor hyperactivity/low compliance, resistance to pharmacological therapy, and candidates for enterocystoplasty. METHODS: From January 2002 to June 2003, a group of 7 patients was selected (4 females, 3 males, mean age, 9.8 years, age range, 5-17 years) with detrusor hyperactivity, clean intermittent catheterization and resistance to pharmacological therapy. Two patients presented with grade 2-3 monolateral vesicoureteral reflux (VUR). All patients were incontinent despite catheterization. Botulinus toxin A was administered under general or local anesthesia by the injection of 200 IU of toxin diluted in 10 cc of physiologic solution with a metal or a flexible needle (3.7 F/21 GA). The needle was fully inserted into the detrusor muscle in about 20 sites, and 0.5 cc of solution were injected in each site, except the trigonum vesicae. Follow-up included ultrasound examination of the urinary tract and urodynamic studies performed at 6, 12 and 24 weeks and biannually thereafter. Micturition cystography was performed 3 months after the intervention. Urodynamic parameters were leak point pressure (LPP), leak point volume (LPV) and specific volume at 20 cm H2O pressure. The results were analyzed using the Wilcoxon test. RESULTS: A significant increase in LPV (range, 30-108%, mean, 77.6%) and in specific volume at 20 cm H2O pressure (CS 20) was observed in all patients. No significant change in LPP was found. One patient previously treated with the Cohen reimplantation technique experienced transient VUR which resolved spontaneously within 1 month. No major side effects from the injection of TB-A occurred. All patients were hospitalized for 24 hours with catheterization. CONCLUSIONS: The preliminary results in this small sample of patients suggest that the use of TB-A is efficacious in significantly improving urodynamic parameters and urine storage volume at low pressures in patients with neuropathic bladder resistant to pharmacological therapy.


Subject(s)
Botulinum Toxins, Type A/therapeutic use , Meningomyelocele/complications , Neuromuscular Agents/therapeutic use , Urinary Bladder, Neurogenic/drug therapy , Adolescent , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/adverse effects , Child , Child, Preschool , Data Interpretation, Statistical , Female , Follow-Up Studies , Humans , Injections, Intramuscular , Male , Meningomyelocele/physiopathology , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/adverse effects , Radiography , Radionuclide Imaging , Time Factors , Treatment Outcome , Urinary Bladder, Neurogenic/diagnostic imaging , Urinary Bladder, Neurogenic/physiopathology , Urinary Incontinence/etiology , Urodynamics , Vesico-Ureteral Reflux/etiology
14.
Surg Endosc ; 2004 Aug 24.
Article in English | MEDLINE | ID: mdl-16467971

ABSTRACT

The laparoscopic one- and two-stage Fowler-Stephens procedure has gained large popularity in the treatment of the child with a high intraabdominal testis. It is largely debated which technique (e.g., testicular autotransplant or Fowler-Stephens procedure) offers the best results for high intraabdominal testes. We describe a case of a 3-year-old boy for whom previous bilateral inguinal exploration results were negative for testes or testicular remnants. The diagnostic laparoscopy showed two iliac intraabdominal testes with short spermatic vessels, closed inguinal rings, and complete dissociation of didime-epididime. A left open orchidopexy was perfomed, and testicular autotransplant was proposed for the right testes located 4 cm from the internal inguinal ring. Long-term follow-up evaluation (1.8 years) of the left testis showed it in the scrotum with good testicular size (1.5 cm). We believe that there are two main reasons to contraindicate the Fowler-Stephens technique: associated malformation that does not permit the development of the collateral blood flow via the vasal artery necessary for a viable testis, and previous surgery that represents a risk factor for testicular atrophy. The laparoscopic anatomic classification for the intraabdominal testis is reliable and can disclose the most suitable surgical technique. Laparoscopy is a valuable tool in the diagnosis and treatment of the nonpalpable testicle.

15.
Mol Cell Biol ; 21(20): 6939-50, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11564877

ABSTRACT

Numerous signaling molecules associate with lipid rafts, either constitutively or after engagement of surface receptors. One such molecule, phospholipase Cgamma-1 (PLCgamma1), translocates from the cytosol to lipid rafts during T-cell receptor (TCR) signaling. To investigate the role played by lipid rafts in the activation of this molecule in T cells, an influenza virus hemagglutinin A (HA)-tagged PLCgamma1 was ectopically expressed in Jurkat T cells and targeted to these microdomains by the addition of a dual-acylation signal. Raft-targeted PLCgamma1 was constitutively tyrosine phosphorylated and induced constitutive NF-AT-dependent transcription and interleukin-2 secretion in Jurkat cells. Tyrosine phosphorylation of raft-targeted PLCgamma1 did not require Zap-70 or the interaction with the adapters Lat and Slp-76, molecules that are necessary for TCR signaling. In contrast, the Src family kinase Lck was required. Coexpression in HEK 293T cells of PLCgamma1-HA with Lck or the Tec family kinase Rlk resulted in preferential phosphorylation of raft-targeted PLCgamma1 over wild-type PLCgamma1. These data show that localization of PLCgamma1 in lipid rafts is sufficient for its activation and demonstrate a role for lipid rafts as microdomains that dynamically segregate and integrate PLCgamma1 with other signaling components.


Subject(s)
Adaptor Proteins, Signal Transducing , Isoenzymes/metabolism , Membrane Microdomains/metabolism , Membrane Proteins , Nuclear Proteins , T-Lymphocytes/enzymology , Type C Phospholipases/metabolism , Acylation , Calcium/metabolism , Carrier Proteins/metabolism , Cell Line , DNA-Binding Proteins/metabolism , Electrophoresis, Polyacrylamide Gel , Enzyme Activation , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Enzymologic , Humans , Immunoblotting , Interleukin-2/metabolism , Jurkat Cells , Luciferases/metabolism , Microscopy, Confocal , Microscopy, Fluorescence , NFATC Transcription Factors , Phospholipase C gamma , Phosphoproteins/metabolism , Phosphorylation , Plasmids/metabolism , Precipitin Tests , Protein Transport , Protein-Tyrosine Kinases/metabolism , Signal Transduction , Subcellular Fractions , Transcription Factors/metabolism , Transcription, Genetic , Transcriptional Activation , Transfection , Tyrosine/metabolism , ZAP-70 Protein-Tyrosine Kinase
16.
Breast Cancer Res ; 2(4): 307-10, 2000.
Article in English | MEDLINE | ID: mdl-11056688

ABSTRACT

Protein truncation test (PTT) and single-strand conformation polymorphism (SSCP) assay were used to scan the BRCA1 and BRCA2 genes in 136 unrelated Italian breast/ovarian cancer patients. In the sample tested, BRCA1 and BRCA2 equally contributed to site-specific breast cancer patients who reported one to two breast cancer-affected first-/ second-degree relative(s) or who were diagnosed before age 40 years in the absence of a family history of breast/ovarian cancer. BRCA1 and BRCA2 mutations were mostly found in patients with disease diagnosis before and after age 50 years, respectively. Moreover, in cases with familial clustering of site-specific breast cancer, BRCA1 mostly accounted for tumours diagnosed before age 40 years and BRCA2 for tumours diagnosed after age 50 years. The BRCA1 and BRCA2 mutation spectrum was consistent with a lack of significant founder effects in the sample of patients studied.


Subject(s)
Breast Neoplasms/genetics , Gene Frequency , Genes, BRCA1 , Neoplasm Proteins/genetics , Neoplastic Syndromes, Hereditary/genetics , Oncogenes , Ovarian Neoplasms/genetics , Transcription Factors/genetics , Adult , Age of Onset , Aged , BRCA2 Protein , Breast Neoplasms/epidemiology , Codon, Nonsense , DNA Mutational Analysis , DNA, Neoplasm/genetics , Female , Genes, Tumor Suppressor , Genetic Predisposition to Disease , Genotype , Humans , Italy/epidemiology , Middle Aged , Neoplastic Syndromes, Hereditary/epidemiology , Ovarian Neoplasms/epidemiology , Polymorphism, Single-Stranded Conformational , Prospective Studies
17.
Int J Oncol ; 17(4): 819-26, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10995897

ABSTRACT

We analyzed 7 mono-, 6 di- and 2 trinucleotide repeat loci in a well characterized series of 69 breast cancer cases, treated in the period 1985-1986 and followed for 12 years. Tumor-associated allele contractions or expansions were observed only at di- and trinucleotide repeats, and were detected in 14/69 cases (20%), of which 7 (10%) showed instability at 2 or more loci (10%). No alterations were detected at mononucleotide repeats known to be unstable in gastrointestinal tumors with the microsatellite mutator phenotype. Disease-free survival at 5 years, overall survival at 12 years of follow-up, tumor stage, estrogen/progesteron receptor status, and expression of the Ki-67 proliferation marker were independent of microsatellite status.


Subject(s)
Breast Neoplasms/pathology , Dinucleotide Repeats/genetics , Trinucleotide Repeats/genetics , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , DNA/genetics , Female , Follow-Up Studies , Genotype , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Middle Aged , Phenotype , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Survival Analysis
19.
Clin Cancer Res ; 2(9): 1601-6, 1996 Sep.
Article in English | MEDLINE | ID: mdl-9816339

ABSTRACT

Deletions and rearrangements involving chromosome 6q have been reported in a number of human cancers such as ovarian and breast tumors as well as melanoma and hemopoietic malignancies. To gain insight into the regions undergoing deletions on the long arm of chromosome 6, we performed a survey of loss of heterozygosity (LOH) at 11 CA repeat markers, mapping from 6q13 to 6q27 in 83 matched sets of tumor and blood DNAs from breast tumor patients. LOH was observed at all tested markers with frequencies ranging from 11.4 to 39.8% of the informative cases, whereas D2S123, a marker linked to the HMSH2 gene mapping in a region rarely presenting allele losses, showed 3.2%. LOH patterns were often complex, with a number of tumors presenting multiple interstitial losses, thus indicating that chromosome 6q can be severely rearranged in breast cancer. Patterns of losses and correlation between LOH occurring at adjacent markers suggested the existence of three (possibly four) distinct regions of allele losses. These were defined by: D6S251-D6S434 (6q13), D6S292-D6S310-D6S314-D6S311 (6q24-q25), and D6S441-D6S281 (6q27). The fourth and more hypothetical region was in the 6q21 region and defined by D6S287-D6S407. Interestingly, the region at 6q24-q25 defined by D6S292-D6S310-D6S314-D6S311 was predominantly observed in evolved and aggressive breast tumors. LOH at D6S314 was correlated with PR- tumors. All together, our data suggest the possible presence of several genes on 6q whose alteration may play a role in breast cancer formation and development.


Subject(s)
Breast Neoplasms/genetics , Chromosomes, Human, Pair 6/genetics , Loss of Heterozygosity , Alleles , Breast Neoplasms/pathology , Chromosome Deletion , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Dinucleotide Repeats , Female , Genetic Markers , Humans , Middle Aged
20.
Biochim Biophys Acta ; 482(2): 379-85, 1977 Jun 10.
Article in English | MEDLINE | ID: mdl-884121

ABSTRACT

An electrophoretically homogeneous preparation of endo-polygalacturonase (poly(1,4-alpha-D-galacturonide)glycanohydrolase, EC 3.2.1.15) from culture filtrates of Rhizoctonia fragariae, a pathogenic agent in strawberry plants, was resolved into two isoenzymes when subjected to isoelectrofocusing in a narrow pH range. The isoelectric points of the two isoenzymes were 6.76 +/- 0.03 and 7.08 +/- 0.05. The two polygalacturonases exhibited similar substrate specificity, pH optimum and pattern of degradation of sodium polypectate. The two enzymes consisted of a single polypeptide chain which had an apparent molecular weight of 36 000 as determined by gel filtration on Sephadex G-100.


Subject(s)
Glycoside Hydrolases , Isoenzymes , Mitosporic Fungi/enzymology , Polygalacturonase , Rhizoctonia/enzymology , Glycoside Hydrolases/metabolism , Isoenzymes/isolation & purification , Isoenzymes/metabolism , Molecular Weight , Polygalacturonase/isolation & purification , Polygalacturonase/metabolism
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