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A Uri

Publications and source records attributed to A Uri.

17 recordsLinked to original sources
PubMed1998

Novel galanin receptor ligands.

Galanin is a neuroendocrine peptide which is 29/30 amino acids in length and is recognised by G-protein-coupled central nervous system receptors via its N-terminus. We synthesised several galanin receptor ligands and fragments around C-terminal extensions of galanin(1-13) to yield chimeric peptides with C-terminals corresponding to bioactive peptides like bradykinin(2-9), mastoparan, neuropeptide Y(25-36) or substance P(5-11), respectively. We also synthesised short galanin analogs in which galanin(1-13) was C-terminally elongated with Lys14; different pharmacologically active small molecules were then attached to the epsilon-amino group of Lys14. Several cysteine-substituted linear and ring closed analogs of galanin(1-9) and galanin(1-16) were also synthesised. The equilibrium binding constants for these peptides at hypothalamic galanin receptors were determined and found in the subnanomolar to micromolar range. The large number of peptides and their binding affinities presented here permit structure-activity relationship analysis of peptide-type ligands to galanin receptors.

Amino Acid Sequence↗
PubMed1996

Peptidyl conjugates of adenosine 5'-carboxylic acid synthesized and evaluated as ligands for P2 purinoceptors.

The role of extracellular ATP in vivo and the various cellular responses mediated by P2 purinoceptors have not yet been fully elucidated, in part depending on the lack of subtype-specific high affinity antagonists. Here we describe the synthesis of a new class of compounds, peptidyl derivatives of adenosine 5'-carboxylic acid, among which some have inhibitory effects in certain P2 purinoceptor-carrying biological systems, e.g., glioma and smooth muscle cell lines and isolated smooth muscle tissue preparations from guinea pig vas deferens and urinary bladder.

Adenosine↗
PubMed1994

A new class of compounds, peptide derivatives of adenosine 5'-carboxylic acid, includes inhibitors of ATP receptor-mediated responses.

A new type of ligand for the study of P2-purinergic receptor subtypes was synthesized by combining and modifying conventional nucleoside chemistry with Fmoc solid phase peptide synthesis techniques. The tri- and tetra-aspartic acid derivatives of adenosine-5'-carboxylic acid (AdoCAsp3 and AdoCAsp4) were found to act as weak agonists at P2-purinergic receptors, (activated by ATP and UTP respectively) present on C6 glioma cells. AdoCAsp4 induced inositol 1,4,5-trisphosphate formation in the C6 cells with an EC50 of 73 microM. In addition, AdoCAsp4 was found to inhibit (IC50 approximately 80 microM) ATP-induced cytosolic [Ca2+] transients in these glioma cells. The glycine derivative, AdoCGly, increased evoked release of noradrenaline from mouse vas deferens slices, probably due to the blockade of presynaptic P2-autoreceptors. The possibility that aspartic, glutamic or gamma-carboxyglutamic residues may be used to replace phosphate groups on an ATP receptor ligand, opens up new ways in ligand design.

Adenosine↗
PubMed1994

Early region 3-replacement adenovirus recombinants are less pathogenic in cotton rats and mice than early region 3-deleted viruses.

BACKGROUND: Adenovirus type-5 (Ad5) recombinant viruses with replacement of the 1.9 kb XbaI fragment in the early region 3 (E3) by foreign genes have been constructed with the ultimate goal of inducing immune responses to the product of the inserted gene against a variety of virus infections. The pathogenicity of these recombinants, however, has not been studied. EXPERIMENTAL DESIGN: Histopathologic changes induced in cotton rat and mouse lung by E3-replacement-Ad5 recombinant or wild-type Ad (Wt-Ad) or E3-deleted mutant (Ad5-delta E3) viruses were compared. Expression of viral mRNA and replication of these viruses in cotton rat and mouse lungs, as well as in human tissue culture cells, were assayed. Expression of class I major histocompatibility complex antigens and the E3-14.7 kilodalton protein in virus-infected cells were also analyzed. RESULTS: An Ad5 recombinant, Ad-human cytomegalovirus glycoprotein B (Ad-HCMV.gB), in which the E3 region is replaced by the full-length gB gene of HCMV and with a genome size exceeding that of Wt-Ad, induced mild histopathologic responses in cotton rat and mouse lungs, comparable with those of Wt-Ad, but less severe than those of Ad5-delta E3. Analysis indicated that neither class I major histocompatibility complex expression on the cell surface nor differential expression of the protective E3-14.7 kilodalton protein underlies the pathologic differences observed in cells infected with Ad5-delta E3 or the Ad-HCMV.gB recombinant. In the mouse lung, another Ad-E3 replacement recombinant, Ad-herpes simplex glycoprotein B (HSV.gB), containing the complete HSV.gB gene and with a genome size larger than that of Wt-Ad, also induced a very mild inflammatory response. However, two recombinants with truncated forms of the HCMV.gB (Ad-HCMV.gB.155) or HSV.gB genes (Ad-HSV.gB.147) produced more severe histopathologic changes than the Wt-Ad or the recombinants with the full complement of HCMV.gB or HSV.gB genes. Ad5 and some of the recombinants replicated in mouse and cotton rat lung, and the extent of replication was inversely proportional to genome size, both in the lung and in human tissue culture cells. Infectious virus titers were, however, higher in cotton rat than in mouse lung. In situ hybridization analysis of cotton rat and mouse lung infected with Wt-Ad, Ad5-delta E3, or Ad-HCMV.gB virus revealed expression of Ad early/late mRNA predominantly in bronchial epithelial cells. CONCLUSIONS: These data not only confirm that E3-deleted viruses induce more severe pathologic changes in cotton rat lungs than Wt-Ad viruses (Ginsberg et al., Proc Natl Acad Sci USA 1989;86:3823-7) but led to the observation that some E3 replacement recombinants also lacking the expression of the 19 and 14.7 kilodalton proteins are significantly less pathogenic in cotton rats and mice than an E3-deleted virus. Pathogenicity and replication of the recombinant viruses inversely correlate with the genomic size.

Adenoviridae↗
PubMed1991

Severe perinatal liver disease and Down syndrome: an apparent relationship.

Down syndrome (DS) is not usually thought of in association with significant infantile liver disease. We present clinical and histopathologic data from 10 patients with DS who presented with severe liver disease at birth or within the first few weeks of life, and summarize the findings of eight previously reported cases. The liver disease was fatal in all but one case. Diffuse lobular fibrosis surrounding proliferating ductular elements and residual hepatocytes characterized the pathologic findings in the liver in all patients. A large number of megakaryocytes were present in the liver in nine of 12 patients. The phenotype of "perinatal hemochromatosis" was documented in eight of nine cases in which the presence of iron was investigated. Since only a fraction of the patients with this phenotype have DS, the patients we describe seem to represent a relatively well-defined subset of the perinatal hemochromatosis phenotype. The existence of such a subset suggests that the perinatal hemochromatosis phenotype does not represent a single etiopathogenetic disorder. The association between DS, megakaryocytic infiltrates in the liver, and fatal subacute/chronic liver disease gives rise to the speculation that fibrosis-promoting factors and/or metabolic abnormalities, such as those resulting from a gene dosage effect, may play a role in the genesis of the liver disease, perhaps due to a particular susceptibility of fetal liver.

Down Syndrome↗
PubMed1989

Hepatoblastoma.

Explore the source record for details and available documents.

Carcinoma, Hepatocellular↗
PubMed1989

Perinatal hemochromatosis: entity or end result?

A clinicopathologic picture of severe neonatal liver disease associated with heavy stainable iron stores in a "hemochromatotic" distribution has been designated as neonatal or perinatal iron storage disease or hemochromatosis. In an attempt to determine the specificity of these findings, we determined the amount and distribution of stainable iron in four groups of autopsied infants: those with severe subacute/chronic liver disease of undetermined etiology, those with subacute/chronic liver disease of known etiology, those with severe acute liver disease, and those with no liver disease. Fourteen of 15 infants with severe subacute/chronic liver disease of unknown etiology showed heavy iron accumulation in a hemochromatotic distribution in more than one organ, in contrast to only one of 37 cases in the other three groups. The findings are compatible with the possibility that the combination of morphologic findings defines a single disease entity (of currently unknown etiology), and also with the possibility that this disease entity is specific only to the extent of establishing a relationship between severe early (in utero) liver injury and a hemochromatotic distribution of iron in multiple organs.

Hemochromatosis↗
PubMed1988

Genetic disorders and major extracardiac anomalies associated with the hypoplastic left heart syndrome.

All pediatric autopsies of patients with hypoplastic left heart syndrome seen during an 11-year interval were reviewed to determine the frequency of underlying chromosomal and single-gene defects and idiopathic major extracardiac anomalies associated with this common, lethal congenital heart abnormality. Of 83 patients identified, nine had underlying chromosomal abnormalities, four had single-gene defects, ten had one or more major extracardiac anomalies without an identifiable chromosomal or mendelian disorder, and two were infants of insulin-dependent diabetic mothers. Overall, 23 patients (28%) had a genetic disorder and/or major extracardiac anomaly. The substantial prevalence of genetic causes of and major extracardiac anomalies associated with hypoplastic left heart syndrome underscores the need for a detailed genetic evaluation for all patients with hypoplastic left heart syndrome.

Abnormalities, Multiple↗
PubMed1987

Malignant ovarian tumors in children and adolescents.

Eighteen patients aged 4 to 18 years (median, 10 years) were treated at the Children's Cancer Research Center of The Children's Hospital of Philadelphia (CHP) from September 1973 to September 1983 for malignant ovarian tumors. The pathologic categories were endodermal sinus tumor (eight patients), embryonal carcinoma (three patients), pure dysgerminoma (three patients), adenocarcinoma (three patients), and malignant granulosa-cell tumor (one patient). In 1973 and 1975, respectively, two patients with endodermal sinus tumors were treated with surgical removal with or without radiation therapy (RT) and chemotherapy with vincristine (Vc) and actinomycin D+ cyclophosphamide + Adriamycin (Adria Laboratories, Columbus, OH) (ACAdr); both developed local recurrence within 12 months and died of tumor. Since 1977, four of six patients with endodermal sinus tumors have been managed successfully with surgery followed by chemotherapy with cisplatin (P), bleomycin (B), vinblastine (Vb), and ACAdr; none received RT. One died of recurrent tumor and the other died of congestive heart failure attributed to Adriamycin (Adr). All three patients with embryonal carcinoma were well after surgical excision alone (one patient) or surgery and chemotherapy with cisplatin + bleomycin + vinblastine (PBVb) + ACAdr (two patients). Treatment of the remaining seven patients included excision alone (two patients) or excision and chemotherapy (five patients) with various combinations of Vc, ACAdr, and P. One patient with granulosa-theca cell tumor also received whole abdominal RT (3000 rad by external beam), and died of congestive heart failure attributed to Adr. The other six children were free of detectable tumor 16 months to 8 years from diagnosis. Chemotherapy with PBVb and actinomycin D + cyclophosphamide (AC) should be used in the postoperative management of young persons with malignant ovarian tumors. Adr is of doubtful value and may be considerably toxic. RT is of limited use and usually is not indicated.

Adenocarcinoma↗
PubMed1987

Nonsurgical management of children with recurrent or unresectable fibromatosis.

At The Children's Hospital of Philadelphia, since 1971, six children 3 months to 17 years of age with fibromatosis have been treated with a combination of vincristine, actinomycin D, and cyclophosphamide (VAC). The first three patients also received radiation therapy (5,500 rads). Locally recurrent tumors developed in four of the children after previous operative removal; the other two had tumors that could not be removed initially. The tumors arose in the neck (three patients), pelvis (two patients), or foot (one patient). In the three patients treated with VAC alone, complete disappearance of tumor was confirmed at second operation in two, and greater than 75% shrinkage on CT scans occurred in the third, all at 4 to 6 months after VAC was started. In two of the three patients who received VAC plus radiation therapy, complete disappearance of tumor occurred at 13 and 16 months; the third had no response. Five of the six patients are free of recurrent fibromatosis at 1, 2, 4, and 11 years after VAC was begun; the sixth has required multiple operations during the last 6 years. We conclude that combination chemotherapy with VAC can produce regression of fibromatosis in some children with recurrent or unresectable lesions. The administration of VAC should be considered for children with fibromatosis in whom operative removal is not feasible, would prove mutilating, or is unlikely to produce long-term control of the disease.

Adolescent↗
PubMed1986

Malignant fibrous histiocytoma of soft tissue in childhood.

Seven children aged 6 months to 11 years with malignant fibrous histiocytoma, a type of sarcoma of soft tissues, have been treated at the Children's Hospital of Philadelphia from January 1975 through July 1983. The primary tumor arose in the head and neck region in three patients, the chest wall in two patients and the pelvis or buttock in one patient each. Operative management consisted of complete tumor removal in the two patients with chest wall tumors, and biopsy only in the remaining five children. Afterward, all seven patients were treated with a multiple-agent chemotherapy program consisting of vincristine, dactinomycin, and cyclophosphamide for two years, with or without Adriamycin (doxorubicin). The five patients with residual tumor also received radiation therapy (RT) in doses of 1500 to 5500 rad. The two children with localized, completely excised sarcoma are continuously free of tumor at 1.4 and 9 years after initiation of treatment. Of the five with residual sarcoma, three had a complete response to radiation and chemotherapy, and two of them are free of recurrence at 4 and 5 years, respectively. In the three remaining children, the tumor spread regionally into the central nervous system or distantly into the lungs, subcutaneous tissues, and liver. Childhood malignant fibrous histiocytoma of soft tissue appears to be similar to childhood rhabdomyosarcoma in its modes of spread and response to management. Operative removal is the key to successful therapy. The roles of multiple-agent chemotherapy and RT remain to be defined. Adriamycin appears to be the most promising single agent. In the absence of concrete data, it seems prudent to follow the same guidelines for irradiation as those used for other soft tissue sarcomas of childhood.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Cancer in neonates: the experience at the Children's Hospital of Philadelphia.

Among 22 neonates treated at the Children's Cancer Research Center of Philadelphia, 11 had neuroblastoma, which in two cases was widely metastatic. There were three infants with teratoma, three with sarcoma, three with leukemia, one with Wilms' tumor, and one with parotid carcinoma. Nine of eleven patients (82%) are long-term survivors following complete surgical excision of tumor, whereas only one of eight (13%) has survived following incomplete surgical excision. All three neonates with leukemia died. The overall two-year actuarial survival is 45% (10/22). The problems associated with treating neonates with chemotherapy, radiation therapy, or both are especially difficult because of the immaturity of the organs and structures. Surgical excision alone has been the treatment of choice for solid tumors. Chemotherapy or radiation therapy, when indicated, require careful monitoring for both acute toxicities and potential long-term morbidities.

Female↗