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Biomedical subjects

J C Murray

Publications and source records attributed to J C Murray.

At least 109 records · Page 6Linked to original sources
PubMed1996

Lymphoblastic lymphoma following prenatal exposure to phenytoin.

PURPOSE: Oncogenesis has been associated with prenatal exposure to phenytoin, concomitant with or independent of the fetal hydantoin syndrome. The majority of reported cases have been embryonal tumors of neural crest origin and have occurred in the first 3 years of life. PATIENTS AND METHODS: We report a boy who was exposed to phenytoin throughout gestation and later developed T-lymphocyte lymphoblastic lymphoma, a previously unreported malignancy associated with in utero phenytoin exposure. Previously reported cases of neoplasia occurring after such exposure are tabulated. CONCLUSION: The actual transplacental oncogenic potential of phenytoin and the epidemiology of this association are poorly understood. Phenytoin-induced alterations in lymphocyte-mediated immunosurveillance or oxidative metabolic clearance may be etiologic. Inquiry into prenatal phenytoin exposure should be done in any child who develops cancer, especially those who develop a rare tumor or present with a more common tumor at an unusually young age. Continued documentation of such cases will advance the understanding of phenytoin-associated transplacental oncogenesis.

Anticonvulsants↗
PubMed1996

Intraabdominal desmoplastic small round cell tumor presenting as a gastric mural mass with hepatic metastases.

PURPOSE: An atypical case of childhood intraabdominal desmoplastic small round cell tumor (DSRCT) is presented. PATIENT AND METHODS: An 11-year-old boy presented with progressive nausea and vomiting, abdominal pain, hepatomegaly, and an epigastric mass. Computed tomographic scanning as well as findings at gastroscopy and laparotomy revealed a large gastric mural tumor accompanied by multiple large intrahepatic masses. Histopathologic examination of biopsy samples revealed evidence of a polyphenotypic neoplasm diagnostic of DSRCT. RESULTS: Unlike most reported cases of DSRCT, no evidence of peritoneal involvement or ascites was detected. Despite an excellent initial response to multiagent chemotherapy, the patient eventually died of progressive tumor. CONCLUSIONS: Though the radiographic and surgical findings in DSRCT usually suggest a mesenteric, peritoneal, or retroperitoneal site of tumor origin, this case demonstrates that intraabdominal DSRCT can present with a primary visceral lesion without evidence of peritoneal or mesenteric involvement or ascites. Combination chemotherapy using vincristine, doxorubicin, cyclophosphamide, cisplatin, and 5-fluorouracil may be of some benefit to patients with this rare tumor.

Abdominal Neoplasms↗
PubMed1996

Renal venous thrombosis complicating acute myeloid leukemia with hyperleukocytosis.

PURPOSE: Leukemic hyperleukocytosis may cause organ- or life-threatening complications. Patients at highest risk appear to be those with acute myeloid leukemia (AML). Blast cell aggregation and thrombus formation in the microvasculature most commonly involves the central nervous system and the pulmonary circulation. We describe a child with AML and renal venous thrombosis (RVT), a previously unreported complication of hyperleukocytosis. PATIENTS AND METHODS: A 17-month-old boy had a white blood cell count of 103 X 10(9) cells/L and RVT (hematuria, arterial systolic hypertension, unilateral nephromegaly, poor renal venous blood flow) at diagnosis of acute myelomonocytic leukemia (AML, FAB M4). CONCLUSION: This case emphasizes the danger of hyperleukocytosis in AML and demonstrates that there may be other organ system dysfunction in addition to the well-described central nervous system and pulmonary complications. Renal venous thrombosis should be considered in the patient with leukemic hyperleukocytosis, hematuria, arterial hypertension, and appropriate radiographic findings. Aggressive cytoreductive measures should be pursued in such cases.

Acute Disease↗
PubMed1996

Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants.

Results of studies to determine whether women who smoke during early pregnancy are at increased risk of delivering infants with orofacial clefts have been mixed, and recently a gene-environment interaction between maternal smoking, transforming growth factor-alpha (TGFa), and clefting has been reported. Using a large population-based case-control study, we investigated whether parental periconceptional cigarette smoking was associated with an increased risk for having offspring with orofacial clefts. We also investigated the influence of genetic variation of the TGFa locus on the relation between smoking and clefting. Parental smoking information was obtained from telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants and with mothers of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening blood spots and genotyped for the allelic variants of TGFa. We found that risks associated with maternal smoking were most elevated for isolated cleft lip with or without cleft palate, (odds ratio 2.1 [95% confidence interval 1.3-3.6]) and for isolated cleft palate (odds ratio 2.2 [1.1-4.5]) when mothers smoked > or =20 cigarettes/d. Analyses controlling for the potential influence of other variables did not reveal substantially different results. Clefting risks were even greater for infants with the TGFa allele previously associated with clefting whose mothers smoked > or =20 cigarettes/d. These risks for white infants ranged from 3-fold to 11-fold across phenotypic groups. Paternal smoking was not associated with clefting among the offspring of nonsmoking mothers, and passive smoke exposures were associated with at most slightly increased risks. This study offers evidence that the risk for orofacial clefting in infants may be influenced by maternal smoke exposures alone as well as in combination (gene-environment interaction) with the presence of the uncommon TGFa allele.

Adult↗
PubMed1996

Exclusion of epidermal growth factor and high-resolution physical mapping across the Rieger syndrome locus.

We have evaluated the 4q25-4q26 region where the autosomal dominant disorder Rieger syndrome has been previously mapped by linkage. We first excluded epidermal growth factor as a candidate gene by carrying out SSCP analysis of each of its 24 exons using a panel of seven unrelated individuals with Rieger syndrome. No evidence for etiologic mutations was detected in these individuals, although four polymorphic variants were identified, including three that resulted in amino acid changes. We next made use of two apparently balanced translocations, one familial and one sporadic, to identify a narrow physical localization likely to contain the gene or to be involved in regulation of gene function. Somatic cell hybrids were established from individuals with these balanced translocations, and these hybrids were used as a physical mapping resource for, first, preliminary mapping of the translocation breakpoints using known sequence tagged sites from chromosome 4 and then, after creating YAC and cosmids contigs encompassing the region, for fine mapping of those breakpoints. A cosmid contig spanning these breakpoints was identified and localized the gene to within approximately 150 kb of D4S193 on chromosome 4. The interval between the two independent translocations is approximately 50 kb in length and provides a powerful resource for gene identification.

Chromosome Mapping↗
PubMed1996

Closing in on the Rieger syndrome gene on 4q25: mapping translocation breakpoints within a 50-kb region.

Rieger syndrome (RGS) is an autosomal dominant disorder of morphogenesis affecting mainly the formation of the anterior eye chamber and of the teeth. RGS has been localized to human chromosome 4q25 by linkage to epidermal growth factor (EGF). We have constructed a detailed physical map and a YAC contig of the genomic region encompassing the EGF locus. Using FISH, several YACs could be shown to cross the breakpoint in two independent RGS patients with balanced 4q translocations. Alu- and LINE-fragmentation of a 2.4-Mb YAC generated a panel of shorter YACs ranging in size from 2.4 Mb to 75 kb. Several fragmentation YACs were subcloned in cosmids, which were mapped to specific subregions of the original YAC by hybridization to the fragmentation panel to further refine the localization of the translocation breakpoints, allowing mapping of the breakpoints to within the most-telomeric 200 kb of the original 2.4-Mb YAC. FiberFISH of cosmids located in this 200-kb region mapped the two translocation breakpoints within a 50-kb region approximately 100-150 kb centromeric to D4S193, significantly narrowing down the candidate region for RGS. The mapping data and resources reported here should facilitate the identification of a gene implicated in Rieger syndrome.

Blotting, Southern↗
PubMed1995

Molecular analysis of nondisjunction in Down syndrome patients with and without atrioventricular septal defects.

BACKGROUND: Congenital heart disease is common in Down syndrome patients, with atrioventricular septal defects accounting for a majority of the abnormalities. The molecular mechanisms of meiotic nondisjunction resulting in Down syndrome were studied for associations with the presence of atrioventricular septal defects. METHODS AND RESULTS: Twenty highly polymorphic chromosome 21 microsatellite markers were used to genotype two groups of patients (group 1: Down syndrome with atrioventricular septal defects, n = 43; and group 2: Down syndrome without cardiac defects, n = 51) to determine (1) the parental origin of the extra chromosome, (2) the stage of meiotic nondisjunction resulting in the trisomy, (3) the presence or absence of disomic homozygosity or heterozygosity, and (4) the degree of recombination in the nondisjoined chromosomes. The parental origin of the nondisjoined chromosome was maternal in 86.2% of the families, with no significant differences between groups. The most centromeric marker was nonreduced, indicating a meiosis I nondisjunction in 76.5% of maternally derived trisomies, and reduced, indicating a meiosis II nondisjunction in 76.9% of paternally derived trisomies, with no significant differences between groups. There were no significant differences in the proportion of reduced markers at any locus between groups. The distribution of the number of crossovers was significantly different between groups (chi 2 = 14.12, P < .001), with less recombination observed in group 1. CONCLUSIONS: In Down syndrome patients, no association was found between the presence of an atrioventricular septal defect and the parent of origin, stage of meiotic nondisjunction, or disomic homozygosity or heterozygosity. A significant association was found between the presence of an atrioventricular septal defect and reduced frequency of recombination.

Case-Control Studies↗
PubMed1995

Genomic organization of the human osteopontin gene: exclusion of the locus from a causative role in the pathogenesis of dentinogenesis imperfecta type II.

Osteopontin (SPP1) is the principal phosphorylated glycoprotein of bone that is also expressed in a limited number of other tissues including dentine. In the current investigation we report the genomic organization of the SPP1 gene, which comprises seven exons, six of which contain coding sequence. The splice sites for exon donor and acceptor positions are in close agreement with previously published consensus sequences. Comparison of the human gene with its murine and bovine counterparts revealed a highly homologous organization. A highly informative short tandem repeat polymorphism isolated at the SPP1 locus showed no recombination with the autosomal dominant disorder dentinogenesis imperfecta type II. Nevertheless, sequencing of each exon in individuals affected by this disorder failed to reveal any disease-specific mutations.

Alleles↗
PubMed1995

Lymphoid malignancies following Kawasaki disease.

Kawasaki disease is a childhood multisystem vasculitic syndrome of unknown etiology. Associated immunological dysregulation is consistently observed and may be pathogenic in the known cardiac and noncardiac complications of the disease. Despite the well-known association between acquired immunodeficiency states and neoplasia, there are no reports of cancer accompanying or following the onset of this disease. We report here two children who were diagnosed with lymphoid malignancies shortly following the diagnosis of Kawasaki disease, suggesting an association between the two entities.

Child↗
PubMed1995

Changes in cartilage composition and physical properties due to stromelysin degradation.

OBJECTIVE: To determine the effects of stromelysin treatment on biochemical, histologic, and swelling characteristics of intact cartilage explants and to correlate these effects with changes in the functional physical properties of the tissue. METHODS: Bovine articular cartilage explants were cultured for up to 3 days in the presence or absence of recombinant human stromelysin (SLN). Damage to matrix proteoglycans and collagens was assessed and characterized by N-terminal sequencing and Western blot analysis, respectively. Explants were mechanically tested to assess the ability of the tissue to withstand cyclic and static compressive loads. RESULTS: Treatment with SLN resulted in a time- and dose-dependent loss of proteoglycans from cartilage explants, with significant loss seen after 3 days of exposure to 20 nM SLN: Histology indicated that initial loss of proteoglycans occurred in regions near the tissue surface and proceeded inward with increasing time of SLN exposure. SLN treatment resulted in degradation of matrix collagen types IX and II, and a concomitant increase in tissue swelling. This matrix degradation resulted in severe alterations in functional physical properties of the tissue, including compressive stiffness. The initial, focal loss of proteoglycans that resulted from SLN treatment was most accurately detected with high-frequency streaming potential measurements. CONCLUSION: Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.

Amino Acid Sequence↗
PubMed1995

Atypical cytogenic aberrations in two childhood peripheral primitive neuroectodermal tumors.

Atypical cytogenetic abnormalities were detected in peripheral primitive neuroectodermal tumors (PPNET) of the extremity in two children. One had an osseous tumor with a balanced reciprocal translocation, t(5;9)(q22;q32), and had a complete response to therapy. The other had a non-osseous tumor with an interstitial deletion, del(18)(q12.2q21.2), was resistant to combination therapy, and at autopsy had evidence of possible clonal evolution with the karyotype 46,XX der(8)t(8;8)(p11.2;q13), inv(16)(p13.2q12),del(18)(q12.2q21.2). Neither tumor demonstrated the t(11;22)(q24;q12) typically found in Ewing's sarcoma and PPNET, suggesting heterogeneity of the cytogenetic aberrations seen in this rare childhood malignancy.

Bone Neoplasms↗