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M Jeffers

Publications and source records attributed to M Jeffers.

51 records · Page 3Linked to original sources
PubMed1995

Wheeze in a heart transplant patient with lymphoma.

We report a case of wheeze in a heart transplant patient who was receiving chemotherapy for a transplant-associated lymphoma. The patient was in severe respiratory distress; there were no radiological abnormalities. A diagnosis of invasive bronchopulmonary aspergillosis was made by bronchoscopy and bronchoalveolar lavage. Despite prompt antifungal therapy the patient died. Wheeze in a non-asthmatic immunocompromised patient, even in the absence of radiological abnormalities, is highly suggestive of invasive bronchopulmonary aspergillosis. Diagnosis is best established by bronchoscopy and examination of the fluid obtained by bronchoalveolar lavage; currently the response to treatment is often disappointing.

Aspergillosis↗
PubMed1994

Identification of multiple promoters within the N-ras proto-oncogene.

N-ras possesses a 'housekeeping' promoter, being G + C-rich and devoid of a TATA-box. Transcription initiates at a number of locations within this gene, a phenomena that is generally attributed to the absence of a TATA-box. In this report we investigate the possibility that multiple promoters, which could potentially contribute to the observed 5' end heterogeneity, exist within the murine N-ras gene. The 5' region of the gene was subdivided into several fragments, each corresponding to a region in which one or more transcription initiation site(s) had been mapped, and the ability of each fragment to express a reporter gene was assessed. Promoter activity was found associated with three independent, non-overlapping fragments, two of which were located entirely within transcribed regions of the gene. We found that these intragenic promoters were able to express the N-ras gene itself, as well as the reporter gene. In addition, we found that the activity of an intragenic promoter fragment was dependent upon the presence of regions encompassing initiation sites, and that a small fragment (approximately 40 bp) encompassing several initiation sites possessed promoter activity. These data support the existence of an 'initiator' element within the N-ras gene. Overall, our results demonstrate that multiple promoters reside within N-ras and suggest that they may play a role in generating the observed mRNA 5' end heterogeneity. The identification of multiple promoters within N-ras may have important implications regarding the regulation of expression of this gene in normal and malignant tissues. In addition, since a number of other genes with housekeeping promoters also initiate transcription at multiple locations, it is possible that the utilization of multiple promoters may represent a common feature of this class of genes.

Animals↗
PubMed1994

Invasive pulmonary aspergillosis associated with low dose methotrexate therapy for rheumatoid arthritis: a case report of treatment with itraconazole.

Opportunistic infections complicating low dose methotrexate therapy are rare, consisting predominantly of Pneumocystis carinii pneumonia. We report a case of invasive pulmonary aspergillosis which developed in a patient being treated for seropositive rheumatoid arthritis with low dose methotrexate (5-7.5 mg weekly) for 8 years. The patient was successfully treated with itraconazole 200 mg daily for 6 months. This case adds to the growing evidence implicating low dose methotrexate with opportunistic infections and should heighten clinical awareness in patients on this treatment.

Aged↗
PubMed1994

Adenovirus 12 E1A gene detection by polymerase chain reaction in both the normal and coeliac duodenum.

A 12 amino acid sequence from the adenovirus 12 E1B protein is homologous at the protein level with a similar 12-mer derived from the wheat protein A-gliadin. It has been suggested that exposure to Ad 12 could sensitise individuals to gliadins with resultant gluten sensitive enteropathy. In this study, the polymerase chain reaction (PCR) was used to analyse duodenal biopsy tissue from patients with coeliac disease for the presence of Ad 12. The sensitivity of the assay system was at least 1 in 10(5) cells and specificity was confirmed both by probing with an internal oligonucleotide and by direct sequencing. Ad 12 sequences were detected in three of 17 patients with adult coeliac disease and in five of 16 adult controls with normal duodenal biopsies. Since exposure to the virus would be predicted to occur in infancy we also studied patients with childhood coeliac disease diagnosed at less than 1 year of age. Ad 12 was positive in three of 10 childhood coeliac patients and one of seven controls. In addition, we studied a cohort of patients who presented with a diarrhoeal illness and associated anti alpha gliadin antibodies in 1983. These patients had duodenal biopsies performed at this time. One of three patients with abnormal histology had detectable Ad 12 while two of 14 with normal findings were positive for Ad 12. Finally, the potential oncogenic nature of Ad 12 prompted examination of a group of patients with intestinal tumours. Ad 12 DNA was, however, in only two of 19 tumour samples tested. These data indicate that Ad 12 can be successfully detected using PCR on paraffin embedded tissue. Furthermore, Ad 12 was detected at a relatively high level in normal duodenum. The results do not, however, support the hypothesis that prior exposure to Ad 12 is implicated in the pathogenesis of coeliac disease.

Adenocarcinoma↗
PubMed1993

Met expression and sarcoma tumorigenicity.

The met protooncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signaling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. However, mouse NIH/3T3 fibroblasts overexpressing Met induce tumor formation in nude mice via an autocrine mechanism (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that human cell lines established from various sarcomas express high levels of activated Met receptor. HGF/SF is also detected in the human sarcoma cell lines but at a reduced level when compared to primary fibroblasts. These properties, high Met expression and reduced ligand levels, are indistinguishable from the properties of NIH/3T3 tumor explant cells overexpressing Met (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992; S. Rong et al., Cell Growth & Differ., 4: 563-569, 1993). Moreover, paraffin-embedded sections of primary tumors from human osteosarcomas, chondrosarcomas, and leiomyosarcoma stain intensely for Met and/or HGF/SF and display extensive tumor cell heterogeneity with regard to both paracrine and autocrine stimulation. On the basis of these findings, we propose that Met-HGF/SF autocrine signaling may contribute to the tumorigenic process in human sarcomas.

3T3 Cells↗
PubMed1992

Multiple intragenic elements regulate the expression of the murine N-ras gene.

We have identified two separate regions within the murine N-ras transcription unit which may participate in the regulation of N-ras gene expression. One of these regions, localized to the first half of intron 1, contains a site of premature transcriptional arrest. We propose that premature transcription termination, which has been identified as an important control mechanism for several genes, may also play a role in the regulation of the N-ras gene. In addition, we have identified a positively acting region within the N-ras transcription unit. This region, localized to the end of intron 1/beginning of exon 1, was found to greatly increase expression from the N-ras promoter.

3T3 Cells↗
PubMed1991

Bleeding due to colorectal atheroembolism. Diagnosis by biopsy of adenomatous polyps or of ischemic ulcer.

Atheroembolism, although not infrequent at autopsy, is seldom identified in life, when it may present as a multisystem disease involving lower limbs, kidney, and gastrointestinal (GI) tract. Diagnosis of isolated GI involvement usually requires examination of surgically resected tissue, because recognition by endoscopic GI biopsy is exceptional. We diagnosed colorectal atheroembolism by biopsy in four patients. All were elderly (68-80 years old) and had generalized atheroma, including aortic aneurysms. Three patients had sudden onset of frank rectal bleeding with clots or bloody diarrhea, lower abdominal discomfort, and tenderness. Biopsy revealed atheroemboli in a rectal ischemic ulcer and in colorectal adenomatous polyps. In all three, disease resolved on conservative management and did not recur during the period of follow-up. In the fourth patient, asymptomatic atheroembolism was identified in an adenomatous polyp at the splenic flexure. Extraintestinal disease attributable to atheroembolism was not present in any of the patients. Atheroembolism with manifestations confined to the colon may sometimes be diagnosed by biopsy, appears to be more frequent than currently recognized, and may present a diagnostic challenge as a self-limited episode of rectal bleeding.

Aged↗
PubMed1990

Characterization of unr; a gene closely linked to N-ras.

The mammalian N-ras gene is believed to play a role in cellular proliferation, differentiation, and transformation. While investigating N-ras, we isolated cDNA's that originate from a closely linked upstream gene. RNase protection assays reveal that this gene, unr, is transcribed in the same direction as N-ras and that its 3' end is located just 130 base pairs away from the point at which N-ras transcription begins. The close spatial relationship between the two genes is conserved in all species from which the N-ras gene has been isolated. An open reading frame, potentially encoding a 798 amino acid protein, is contained within the unr cDNA. Neither the primary protein structure nor the nucleic acid sequence of unr is homologous to any other known gene, including N-ras. Unr transcripts are detected in mouse, rat and human cells, and Southern analysis indicates that the unr locus found immediately upstream of the N-ras gene is transcriptionaly active in the mouse since only a single copy of unr is detected in this species. Unr produces multiple transcripts that differ in their 3' ends and are apparently created through the differential use of multiple polyadenylation sites located in the 3' untranslated region of the gene. Both unr and N-ras are expressed in all tissues examined. In the testis, both genes are developmentally regulated, with an increase in expression occurring upon testicular maturation. Thus the two genes may be coordinately regulated, at least in certain circumstances. Our findings suggest that a thorough analysis of the relationship that exists between the two genes could potentially provide insights into the regulation and/or function of N-ras.

Amino Acid Sequence↗
PubMed1986

Granulocytopaenia and thrombocytopaenia in dairy cattle--a suspected mycotoxicosis.

During a 6-week period, 22 Dairy Shorthorn cows and heifers died with granulocytopaenia and thrombocytopaenia. Clinical signs observed in the affected animals included increased salivation, pyrexia, depression, rumenal stasis, bilateral epistaxis, melaena, increased bleeding after removal of retained foetal membranes and rapid weight loss. Despite intensive antibiotic and vitamin K therapy and blood transfusions, all affected animals died. The aetiological agent, thought to be a fungal toxin, could not be isolated from post mortem specimens or pasture samples.

Agranulocytosis↗
PubMedDate not supplied

Primary abdominal wall clear cell carcinoma arising in a Caesarean section scar endometriosis.

BACKGROUND: Endometriosis occurring in a surgical scar is well recognized and occurs mainly in patients with a history of hysterectomy or Caesarean section. Scar endometriosis, as well as endometriosis at other sites, can undergo malignant change. Endometrioid carcinoma is the most common malignant tumour arising in endometriosis. However, clear cell carcinoma can also occur but is unusual. AIM: To discuss the diagnosis and management of such a case. METHODS: We report a case of primary clear cell carcinoma in endometriosis of a Caesarean section scar and review the literature. RESULTS: The patient presented with a large right lower quadrant abdominal wall mass within a Caesarean section scar. Histological examination revealed a clear cell carcinoma. The patient had a prior history of pelvic endometriosis. According to the Irish National Cancer Registry, this is the first reported case of a primary abdominal wall clear cell carcinoma developing within a Caesarean section scar in Ireland. CONCLUSION: Any lesion occurring in a Caesarean section scar with a history of previous endometriosis cannot be underestimated and warrants careful clinical follow-up and histological evaluation as appropriate.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Unusual presentation of an appendiceal malignancy.

Primary malignant epithelial tumors of the appendix are uncommon. The most common presentation of appendiceal malignancy is right lower abdominal pain suggestive of acute appendicitis. Presentation caused by loco-regional spread with involvement of neighboring organs is rare. We present the case of a 48-year-old woman with an appendiceal malignancy who presented with symptoms and signs suggestive of complicated diverticular disease with an enterovaginal fistula. From a review of the literature, this is the first report of an appendiceal malignancy presenting in this manner.

Adenocarcinoma, Mucinous↗