Biomedical subjects

M Burrell

Publications and source records attributed to M Burrell.

At least 19 recordsLinked to original sources

PubMed1997

Analysis of multiple copies of geminiviral DNA in the genome of four closely related Nicotiana species suggest a unique integration event.

Previously, we discovered multiple direct repeats of geminivirus-related DNA (GRD) sequences clustered at a single chromosomal position in Nicotiana tabacum (tobacco). Here we show that, in addition to tobacco, multiple copies of these elements occur in the genomes of three related Nicotiana species, all in the section Tomentosae: N. tomentosiformis, N. tomentosa and N. kawakamii, but not in 9 other more distantly related Nicotiana species, nor in various other solanaceous and non-solanacous plants. DNA sequence analysis of 18 GRD copies reveal 4 distinct, but highly related, sub-families: GRD5, GRD3 and GRD53 in tobacco; GRD5 in N. tomentosiformis and N. kawakamii; and GRD2 in N. tomentosa. In addition to novel sequences, all elements share significant but varying lengths of DNA sequence similarity with the geminiviral replication origin plus the adjacent rep gene. There is extended sequence similarity to REP protein at the deduced amino acid sequence level, including motifs associated with other rolling circle replication proteins. Our data suggest that all GRD elements descend from a unique geminiviral integration event, most likely in a common ancestor of these Tomentosae species.

Amino Acid Sequence↗

PubMed1997

Decreased immunoglobulin deposition in tumors and increased immature B cells in p53-null mice.

Recent studies have hinted that there may be a relationship between p53 and the immune response. In preliminary experiments, we found significantly decreased levels of immunoglobulin deposition in 13 of 16 p53-null tumors compared with 2 of 17 tumors derived from p53 +/- mice. We further explored the effect of p53 on B-cell development and function. p53-null mice contained more splenic white pulp and more immature B cells in the bone marrow compared with p53 +/- mice. p53-null B cells were hyperresponsive to proliferative challenge but were not more resistant to signal-induced apoptosis. Several p53 DNA-binding sites were localized to the regulatory regions of immunoglobulin heavy and light chain genes, including the KII site, which serves as an enhancer for rearrangement of the mouse kappa chain J cluster genes. Levels of p53 protein and the kappa chain sterile transcript increased after exposure of pre-B cells to the DNA damaging agents etoposide and Adriamycin. Our observations suggest that p53 may be involved in B-cell maturation and may relay certain stress signals to affect B-cell function.

Animals↗

PubMed1996

Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues.

Hereditary nonpolyposis colorectal cancer is caused by inherited mutations of mismatch repair genes. We developed monoclonal antibodies to the prototype human mismatch repair gene hMSH2 and used them to detect an immunoreactive protein of M(r) 100,000 in mismatch-proficient cell lines. In addition, a M(r) 150,000 protein coimmunoprecipitated with the hMSH2 gene product in cell lines expressing hMSH2. Immunohistochemistry demonstrated that the hMSH2 protein was exclusively nuclear. Whereas the hMSH2 protein was expressed in a variety of tissues, the most striking pattern was observed in esophageal and intestinal epithelia, where expression was limited to the replicating compartment. Neoplastic cells within benign and malignant mismatch repair-proficient tumors expressed the protein, but no hMSH2 immunoreactivity was observed in the colorectal tumors of patients with germline hMSH2 mutation. These results have implications for tumorigenic mechanisms and, potentially, for diagnosis.

Animals↗

PubMed1995

APC binds to the novel protein EB1.

Mutations of the APC gene play a critical role in both sporadic and familial forms of colorectal cancer. The vast majority of these mutations result in the loss of the carboxyl terminus of the protein. To further elucidate the function of APC, we searched for cellular proteins that associate with its carboxyl terminus. One million human cDNA clones were screened with the use of the interaction trap two-hybrid system, and 67 clones were found to have a phenotype suggestive of an APC-interacting protein. Nucleotide sequence analysis revealed that 48 of these clones were derived from a single novel named EBI. The association of APC and EB1 proteins was confirmed with in vitro binding assays. mAbs against EB1 were then produced and used to demonstrate the association of APC and EB1 in vivo. The EB1 gene was predicted to encode a 268-amino acid protein without significant homology to proteins with known function. However, searches of nucleotide databases did identify evidence for at least two related human genes and a yeast homologue. This conservation suggests an essential function for EB1 that might provide clues to the mechanism through which APC suppresses colonic neoplasia.

Adenomatous Polyposis Coli Protein↗

PubMed1995

Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues.

The p53-regulated gene product p21WAF1/CIP1 is the prototype of a family of small proteins that negatively regulate the cell cycle. To learn more about p21WAF1/CIP1 regulation in vivo, monoclonal antibodies were developed for immunohistochemistry. These revealed that p21WAF1/CIP1 expression followed radiation-induced DNA damage in human skin in a pattern consistent with its regulation by p53. A detailed comparison of the human, rat, and mouse p21WAF1/CIP1 promoter sequences revealed that this induction was probably mediated by conserved p53-binding sites upstream of the transcription start site. In unirradiated tissues, p21WAF1/CIP1 expression was apparently independent of p53 and was observed in a variety of cell types. Moreover, there was a striking compartmentalization of p21WAF1/CIP1 expression throughout the gastrointestinal tract that correlated with proliferation rather than differentiation. As epithelial cells migrated up the crypts, the Ki67-expressing proliferating compartment near the crypt base ended abruptly, with the coincident appearance of a nonproliferating compartment expressing p21WAF1/CIP1. In colonic neoplasms, this distinct compartmentalization was largely abrogated. Cell cycle inhibitors are thus subject to precise topological control, and escape from this regulation may be a critical feature of neoplastic transformation.

Adenoma↗

PubMed1995

Adenosine diphosphate glucose pyrophosphorylase genes in wheat: differential expression and gene mapping.

A full-length cDNA clone representing the large (shrunken-2) subunit of ADP-glucose pyrophosphorylase (AGP; EC 2.7.7.27) has been isolated from a cDNA library prepared from developing grain of hexaploid wheat (Triticum aestivum L., cv. Chinese Spring). The 2084-bp cDNA insert contains an open reading frame of 1566 nucleotides and primer-extension analysis indicated that the 5' end is 10 nucleotides shorter than the mRNA. The deduced protein contains 522 amino acids (57.8 kDa) and includes a putative transit peptide of 62 amino acids (6.5 kDa). The similarity of the deduced protein to the small subunit of AGP and to other AGP genes from plants and microorganisms is discussed. Northern hybridisation shows that the Agp1 genes (encoding the small subunit in the wheat endosperm) and the Agp2 genes (encoding the large subunit in the wheat endosperm) are differentially expressed in the wheat grain. Transcripts from both gene sets accumulate to high levels in the endosperm during grain development with the majority of the expression in the endopsperm rather than the embryo and pericarp layers. Although enzyme activity is detected in developing grains prior to 10 d post anthesis, only the Agp1 genes are active at this time (the Agp2 genes are not expressed until 10 d post anthesis). The possibility that the enzyme expressed during early grain development is a homotetramer of small subunits is discussed. The Agp1 and Agp2 genes are arranged as triplicate sets of single-copy homoeoloci in wheat. The Agp2 genes are located on the long arms of chromosomes 1A, 1B and 1D, about 80 cM from the centromere. The Agp1 genes have been mapped to a position just distal to the centromere on the long arms of chromosomes 7A, 7B and 7D.

Amino Acid Sequence↗

PubMed1995

Multiple focal nodular hyperplasia of the liver associated with hemihypertrophy and vascular malformations.

A case of multiple focal nodular hyperplasia of the liver occurring in a 22-year-old woman with musculoskeletal hemihypertrophy and anomalous vascular supply to the liver is described. The patient had Klippel-Trénaunay-Weber syndrome and abdominal pain and tender massive hepatomegaly. Visceral angiography showed marked dilatation of the celiac axis and both the main trunk and peripheral branches of the hepatic artery. Large abdominal veins drained from the dome of the liver into the hepatic veins. The vascular anomalies were evident on contrast-enhanced computed tomography and magnetic resonance imaging. Multiple focal nodular hyperplasia was confirmed by laparoscopic liver biopsy. The findings in this patient support the concept that multiple focal nodular hyperplasia characteristically occurs in a syndromic form and is induced by an irregular arterial supply in the liver, with localized hyperfusion that leads to nodular areas of hepatocyte hyperproliferation.

Adult↗

PubMed1995

Endocrine tumors of the small and large intestine.

Among endocrine tumors arising in the intestinal tract, midgut argentaffin EC cell carcinoids, duodenal gastrin cell tumors and rectal trabecular L cell carcinoids, in order of decreasing frequency, are those better represented. Together they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas and poorly differentiated neuroendocrine carcinomas, are also well defined tumor entities. The carcinoid syndrome with intermittent flushing, hypotension and diarrhea, and the Zollinger-Ellison syndrome with severe peptic ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome arises in about 10% of intestinal carcinoids, usually in their advanced metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of gastrin cell tumors, including small intramural growths. Tumor prognosis depends on mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases) and associated clinical syndrome or background disease.

Humans↗

PubMed1994

WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis.

The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells.

Alleles↗

PubMed1993

p53 Mutation and MDM2 amplification in human soft tissue sarcomas.

The p53 and MDM2 genes were analyzed in 24 human soft tissue sarcomas (11 malignant fibrous histiocytomas and 13 liposarcomas). Alterations of p53, consisting of point mutations, deletions, or overexpression, were detected in one-third (8 of 24) of the sarcomas. MDM2 gene amplification was detected in another 8 tumors, but no tumor contained an alteration of both genes. Monoclonal antibodies reactive with the human MDM2 gene product were developed, and immunohistochemical analysis revealed nuclear localization and overexpression of MDM2 in those tumors with amplified MDM2 genes. These data support the hypothesis that p53 and MDM2 genetic alterations are alternative mechanisms for inactivating the same regulatory pathway for suppressing cell growth.

Animals↗

PubMed1993

Enterocolic lymphocytic phlebitis. Clinical, radiologic, and pathologic features.

Venous compromise as a cause of ischemic colitis and enteritis is infrequent. Enterocolic lymphocytic phlebitis, a rare cause of such compromise, to our knowledge has been reported in only three patients. We describe a patient with this condition who had hematochezia and a cecal mass that was mistaken endoscopically and radiologically for carcinoma and required resection. The mass, which was ulcerated, was due to intense submucosal edema. The patient had no history of taking hydroxyethylrutoside, a drug used in Europe in treating varicose veins that has been implicated in all three previously reported cases. This entity is characterized by a mixed T- and B-cell vasculitis affecting veins exclusively in the wall and mesentery of the colon and small bowel, without systemic involvement, leading to fibrointimal proliferation, thrombosis, venous occlusion, and subsequent edema and ischemic necrosis. It should be distinguished from other enterocolic phlebitides, including Behçet disease, systemic lupus erythematosus, and myointimal hyperplasia of mesenteric veins, and can be treated by local excision of the affected bowel.

Aged↗

PubMed1992

Achalasia and hiatal hernia.

Several reports have emphasized the rarity of hiatal hernia in achalasia, despite the lack of inherent incompatibility of the two conditions and despite the relatively high frequency of hiatal hernia in the general population. We reviewed the radiographs of 71 of 94 consecutive patients with manometrically proven achalasia referred to Yale-New Haven Hospital. Unequivocal hiatal hernia was seen in 10 (14.1%) patients and was seen in nine of 35 (25.7%) patients 51 years old or more. Review of the radiographic reports from these 10 patients indicated that only two were properly recognized as showing both achalasia and hiatal hernia. All five patients who underwent pneumatic dilatation had excellent results. We conclude that hiatal hernia in achalasia is frequently unrecognized and underreported but is not rare, with a frequency probably similar to that of the general population.

Adolescent↗

PubMed1992

Laparoscopically-assisted hysterectomy for the management of a borderline ovarian tumor: a case report.

Borderline ovarian tumors account for 4% of ovarian neoplasms, an incidence which remains constant despite advancing age. Management for younger women can be unilateral oophorectomy, although simple hysterectomy with bilateral salpingo-oophorectomy is more appropriate for women beyond childbearing age. The authors report a laparoscopic approach to a case of borderline ovarian tumor.

Adult↗

PubMed1991

Expression of an antisense viral gene in transgenic tobacco confers resistance to the DNA virus tomato golden mosaic virus.

Transgenic tobacco plants carrying a genetic cassette including an antisense DNA sequence of the virally encoded AL1 gene of the geminivirus tomato golden mosaic virus (TGMV) were constructed; AL1 encodes a protein absolutely required for TGMV DNA replication. These genetic cassettes also contained, on the same transcription unit, a gene encoding hygromycin resistance, which allowed selection for concomitant expression of the antisense gene. In transgenic lines, RNA transcripts of the predicted size and strand specificity were detected in antisense plants and sense controls. After infection of plants with TGMV, by agroinoculation, the frequency of symptom development was very significantly reduced in a number of antisense lines and correlated, broadly, with the abundance of antisense RNA transcript and with a reduction in viral DNA harvested from infected leaf tissue. We used an in vitro assay to study viral DNA replication in the absence of cell-to-cell spread; no replication was seen in five of the six antisense lines studied, in contrast to controls.

DNA Viruses↗

PubMed1991

Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings.

Compared with classic achalasia, vigorous achalasia has been defined as achalasia with relatively high esophageal contraction amplitudes, often with minimal esophageal dilation and prominent tertiary contractions on radiographs, and with the presence of chest pain. However, no study using current manometric techniques has compared manometric, radiographic, and clinical findings in vigorous and classic achalasia or questioned the usefulness of making this distinction. Fifty-four cases involving patients with achalasia whose radiographic and manometric studies were performed within 6 months of each other were available for review. Patients with vigorous achalasia (n = 17), defined by amplitude greater than or equal to 37 mm Hg, and patients with classic achalasia (n = 37), defined as amplitude less than 37 mm Hg, had substantial overlap in radiographic parameters of esophageal dilation, tortuosity, and tertiary contractions. Manometric properties of repetitive waves and lower esophageal sphincter pressure and clinical aspects of chest pain, dysphagia, heartburn, and satisfactory responses to pneumatic dilation were similar in both forms of achalasia. A separate analysis of patients with mean contraction amplitude greater than 60 mm Hg revealed similar findings. It is concluded that use of amplitude as a criterion for classifying achalasia is arbitrary and of dubious value.

Adult↗

PubMed1989

Recurrent cholangitis secondary to oriental cholangiohepatitis.

A Korean woman with a known mass in the left lobe of the liver and a normal gallbladder by ultrasound suffered recurrent cholangitis, which ultimately proved to be Oriental cholangiohepatitis. This disease, endemic to East Asia, has become widespread in the United States as immigration from that area has increased. The symptoms are identical to recurrent cholangitis associated with gallstones, but the natural history and definitive treatment are entirely different. The diagnosis should be suspected in patients with a history of parasitic infestation with Ascaris lumbricoides or Clonorchis sinensis or in those who have lived in an endemic area.

Adult↗

PubMed1988

The forgotten surgical foreign body.

Instruments and drains left in the abdomen following surgery may be responsible for bizarre and varied complications. The patient may remain asymptomatic for months or even years. Complications include adhesion formation, intestinal obstruction, abscesses, and erosion into the gastrointestinal tract. We report 3 patients in whom retained surgical material eroded into the duodenum and colon, respectively, and produced unusual radiologic findings and complications.

Adult↗

PubMed1983

Ureterosigmoidostomy: the development of tumors, diagnosis, and pitfalls.

The development of colon carcinoma after ureterosigmoidostomy has not received adequate attention in the radiologic literature. Two patients who had ureterosigmoidostomy and subsequently developed tumors are described. The third case is a patient with a ureterosigmoidostomy and a ureterocele that simulated the appearance of carcinoma in the sigmoid colon. This is the first report of this entity. Ureterosigmoidostomy patients need frequent follow-up studies since their incidence of carcinoma is significant. The use of barium to study the colon in this group of patients is controversial. Barium can potentially reflux into the kidney with fecal material, which can lead to fibrosis and impaired renal function. However, barium reflux up the ureter is usually of no significance except on those rare occasions when intrarenal reflux occurs and inflammatory changes may develop. The diagnosis of tumors in these patients, diagnostic pitfalls, and controversy regarding use of barium enemas in following these patients are discussed.

Adult↗