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Biomedical subjects

M Troster

Publications and source records attributed to M Troster.

18 recordsLinked to original sources
PubMed1996

Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases.

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.

Adenocarcinoma↗
PubMed1996

Intestinal mucosal permeability to 51Cr-ethylenediaminetetraacetic acid is increased after bilateral lower extremity ischemia-reperfusion in the rat.

BACKGROUND: Despite successful revascularization of ischemic extremities, multiorgan dysfunction syndrome develops in some patients. Mechanisms responsible for this are not known; however, the gastrointestinal tract has been implicated as a possible mediator. Our objective was to demonstrate increased intestinal mucosal permeability after bilateral hindlimb ischemia-reperfusion (I-R) in a rodent model. METHODS: Sixteen male Wistar rats were randomized either to 4 hours of bilateral hindlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or control groups (n = 8). The animals received 10 MuCi 51Cr-ethylenediaminetetraacetic acid (EDTA) by gavage, and excretion was measured in urine collected every 8 hours in 16 animals and every 4 hours in 8 animals. Arterial blood pressure was monitored continuously. Intravenous normal saline solution (3 ml/hr) with fentanyl (2 microgram/100 gm/hr) was continuously administered. Immediately before death complete blood count and levels of arterial lactate, creatinine, and urea were obtained. Mesenteric lymph nodes were harvested from the ileocecal region and cultured. Distal small bowel and proximal colon were preserved for histologic analysis. An additional 11 rats, six experimental and five control, were evaluated for mesenteric lymph node cultures only. RESULTS: Urinary excretion of 51Cr-EDTA was significantly greater in the I-R group between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of reperfusion. This increase occurred as early as 4 to 8 hours of reperfusion (p < 0.0001). Urine volume in the I-R group was significantly reduced during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin and lactate level were significantly different in the I-R group. Leukocyte and platelet counts, levels of creatinine and urea, and colony counts from mesenteric lymph nodes were similar in I-R and control groups. Blinded histologic analysis of bowel segments did not reveal morphologic differences. CONCLUSIONS: Bilateral hindlimb I-R produces remote intestinal mucosal injury shown by significantly increased permeability to 51Cr-EDTA. Such increased mucosal permeability may be important in the development of multiorgan dysfunction syndrome in patients who sustain lower extremity I-R injury.

Animals↗
PubMed1994

p53 immunoreactivity in carcinosarcoma of the esophagus.

The case of a primary esophageal carcinosarcoma, shown to express p53 protein, is presented. The patient, a 57-year-old male, presented with fever, weight loss, and clubbing, but without swallowing difficulties. A large intraesophageal tumor was found on radiologic imaging, and sarcoma was diagnosed on esophagoscopic biopsy. Despite total esophagectomy and adjuvant chemo-radiotherapy, pleural metastases developed 3 months postoperatively. Histologically, the tumor was composed of epithelial and sarcomatous elements. Using monoclonal and polyclonal anti-p53 antibodies, p53 protein was distributed heterogenously throughout the sarcomatous elements of the primary tumor. Immunoreactivity was also found in regional lymph node metastases. These observations further implicate the p53 tumor suppressor gene in the pathogenesis of human esophageal cancers.

Carcinosarcoma↗
PubMed1994

Clinical implications of p53 gene mutation in the progression of Barrett's epithelium to invasive esophageal cancer.

The p53 tumor suppressor gene has been implicated in human esophageal tumorigenesis, and mutations are reported in primary esophageal adenocarcinomas and associated Barrett's epithelium. To evaluate the potential clinical significance of this molecular genetic marker in the progression of Barrett's epithelium to invasive esophageal cancer, we studied 20 patients with Barrett's epithelium, 10 of whom had an associated adenocarcinoma. p53 gene mutations were screened using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis and p53 oncoprotein distribution by immunohistochemistry. Point mutations were localized to exons 5 and 7 of the p53 gene, previously recognized as "hot spots." p53 gene mutations and immunoreactivity were detected in 7 of 10 patients with primary esophageal adenocarcinomas and in 6 patients with associated Barrett's epithelium, 3 of whom had high-grade dysplasia. Little correlation was observed between p53 positivity and clinicopathologic findings or outcome, although two patients with p53 mutations subsequently developed second primary cancers. Of 10 patients with Barrett's epithelium alone, 6 had p53 mutations, with mild or no dysplasia histologically, suggesting that p53 gene mutation may be an early event in progression to invasive cancer. No patient has developed invasive cancer to date, with a median follow-up of 8 years. These studies further implicate the p53 gene in the Barrett's epithelium-to-carcinoma sequence. Prospective surveillance studies incorporating molecular analysis of the p53 gene are warranted to further evaluate p53 as a predictor of patients at high risk for developing malignancy.

Adenocarcinoma↗
PubMed1994

p53 and ras gene expression in human esophageal cancer and Barrett's epithelium: a prospective study.

To assess potential clinical applications for molecular genetic markers associated with human esophageal tumorigenesis, ten patients with primary esophageal adenocarcinomas were studied prospectively to evaluate expression of the p53 and H-ras genes. Total RNA was extracted from tumor, Barrett's epithelium, and histologically normal esophageal mucosa obtained at surgical resection, and gene expression investigated by Northern blot analysis. p53 was overexpressed, relative to normal tissue from the same patient, in seven tumor and six Barrett's specimens, whereas high levels of H-ras were found in only four tumor and one Barrett's specimen. Clinical correlative data were obtained for all patients, with a median follow-up of 14 months. Advanced pathologic stage was associated with poor survival. No association was found between gene expression and outcome. Three patients with low p53 and H-ras levels developed metastatic disease 7 to 12 months following resection. We conclude that both p53 and ras are implicated in the progression of Barrett's epithelium to invasive cancer, and that further clinical correlative studies are warranted to evaluate potential clinical application for such molecular markers.

Adenocarcinoma↗
PubMed1993

Medullary thyroid carcinoma: prognostic factors.

Medullary thyroid carcinoma is an uncommon cancer of the thyroid gland. It comprises a neuroendocrine tumor of the calcitonin secreting cells. Its level of aggressiveness lies between that of well-differentiated and anaplastic thyroid malignancies. We have undertaken a retrospective study of 18 patients with medullary thyroid carcinoma to evaluate various parameters for their prognostic value. We looked at epidemiologic factors such as stage, age at onset, sex and the heredity of the disease. In addition various immunohistochemical stains were looked at including Leu-M1, calcitonin, thyroglobulin, somatostatin, carcinoembryonic antigen, neuron specific enolase and BRST-1. Finally, DNA ploidy was determined using the flow cytometer. Stage, age at onset, DNA ploidy and staining for BRST-1 were found to be significant factors in determining outcome of this disease.

Adolescent↗
PubMed1990

The prognostic significance of tumor ploidy and pathology in adenocarcinoma of the esophagogastric junction.

Tumor DNA content has been advocated to be an important prognostic indicator in human malignancies. Paraffin-embedded specimens of 75 resected adenocarcinomas (AC) of the esophagogastric junction were studied by flow cytometric DNA analysis to determine whether tumor ploidy was a significant prognostic variable independent of stage and histologic grade of the tumor. Eighty-one percent of the tumors were aneuploid. More patients with aneuploid tumors had lymph node metastases than patients with diploid tumors (P = 0.007). Patients with aneuploid tumors had poorer 18-month disease-free and overall survival than patients with diploid tumors. Cox regression analysis demonstrated that the most important prognostic variables for predicting overall survival were lymph node status, depth of wall invasion, and tumor differentiation. Tumor ploidy was not an independent prognostic variable in predicting recurrent disease or death from AC of the esophagogastric junction. Tumor DNA content is valuable, however, as a marker for patients at increased risk of lymph node metastases, early recurrence, and poorer survival.

Adenocarcinoma↗
PubMed1990

Histologic and ultrastructural changes in nonpulmonary organs during early hyperdynamic sepsis.

Previous studies describing the histologic elements of multi-system organ failure caused by bacterial sepsis may have been complicated by a significant interaction on tissue injury from either a preterminal low-flow state or the effects of therapy immediately before death. Therefore we evaluated the nonpulmonary histologic findings of sepsis during a 3-day period that followed cecal ligation and perforation. In this septic model, mean arterial perfusion pressures remained unchanged from baseline, systemic flows rose by 54%, and laboratory evidence of organ dysfunction including an elevation of the serum bilirubin levels and a depression of the serum total protein values was considered mild. Concurrently, development of the hyperdynamic central circulatory septic state was associated with widespread histologic changes in myocardium, striated muscle, liver, gut, and pancreas. Lesions common to these organs included high-protein interstitial and intracellular edema, mitochondrial destruction, and patchy cell necrosis. Lesions within the pancreas were exaggerated over those noted in other organs. Of all organs examined, only the liver demonstrated microvascular neutrophil accumulation. Unlike models of shock caused by sepsis, fibrin thrombi were not seen in the microvasculature of any organ. We conclude that tissue injury characterized by the accumulation of protein-rich extravascular fluid and the development of reversible and irreversible cell injury antedated significant multiple-system organ failure in this animal model of normotensive sepsis.

Animals↗
PubMed1988

Calcitonin and chromogranin A localization in medullary carcinoma of the thyroid by immunoelectron microscopy.

We used a post-embedding immunoelectron microscopy method, using protein A-gold, to detect calcitonin and chromogranin A immunoreactivity in three cases of human medullary thyroid carcinoma. Because the epoxy-embedded tissue had been fixed (glutaraldehyde or formaldehyde) and osmicated before embedment, the proteins were identified in optimally preserved tissue. Uranyl and lead staining was used after immunolabeling, so that the tissue was also optimally contrasted. The morphological advantage provided by osmication was tested by labeling rat thyroid gland C-cells for calcitonin. The protein A-gold technique allowed localization of both antigens to the contents of membrane-bound secretory granules in the tumor cells. In one case, labeling density for each antigen was measured over several intercellular compartments and the interstitium. Calcitonin, but not chromogranin A, reactivity was also identified in intracellular amyloid fibrils in two cases, showing that the constant region of calcitonin is preserved in amyloid deposits related to the tumor cells.

Calcitonin↗
PubMed1986

Increased activity on immediate phase of bone imaging does not always indicate increased blood volume.

The immediate Tc-99m MDP image of a neoplastic right wrist mass in a 10-year-old boy demonstrated intense focal accumulation that suggested a very vascular tumor, but delayed images showed only slightly increased activity in the mass. A Tc-99m labeled RBC study was performed to permit whole-body blood pool imaging for other vascular lesions, and it did not demonstrate an increased blood volume in the mass. Biopsy showed the tumor to be a Ewing's sarcoma, probably of soft tissue origin. The sarcoma was not very vascular. The intense immediate accumulation of Tc-99m MDP in this case may be attributed to increased microvascular permeability.

Biopsy↗
PubMed1985

Changes in immunohistochemical staining in prostatic adenocarcinoma following diethylstilbestrol therapy.

Twenty-eight pretreatment and posttreatment biopsies from 11 cases of prostatic adenocarcinoma were stained for prostate-specific acid phosphatase (PAP), prostate-specific antigen (PSA), and keratin to determine the effect of hormonal (diethylstilbestrol) therapy on these immunological markers. Treatment intervals ranged from 2 to 63 months. All pretreatment tumors were strongly positive for PAP, and nine were strongly positive for PSA. Two were weakly positive for PSA, and all were negative for keratin. In five of the 11 posttreatment group cases, staining with both PAP and PSA was reduced. In three posttreatment cases, the malignant epithelium showed a squamoid appearance, and in these areas the keratin gave a positive reaction. These findings indicate that immunohistochemical staining with PAP and PSA may change in response to hormonal therapy. These alterations may lead to false-negative results when using these techniques to identify the primary tumor source of metastatic deposits of prostatic carcinoma.

Acid Phosphatase↗
PubMed1979

The significance of urine phosphate measurements in the early diagnosis of intestinal infarction.

This study has confirmed previous experiments which indicated that inorganic phosphate concentrations rise in body fluids after intestinal infarction. The phosphate clearance ratio is elevated in dogs after occlusion of the superior mesenteric artery, but is not as sensitive as indicator of the presence of a necrotic intestine as the serum or peritoneal fluid phosphate levels. The rise and fall of phosphate levels occur within the first 24 hours after infarction, similar to amylase levels in acute pancreatitis. The renal failure observed in dogs after ligation of the superior mesenteric vein is likely on the basis of hypovolemia and does not seem to result from hyperphosphatemia. Intestinal infarction should be suspected with laboratory evidence of hemo-concentration, marked leukocytosis, an inappropriate metabolic acidosis and elevated serum and peritoneal fluid phosphate levels. In dogs with normal renal function, an elevated urinary phosphate clearance ratio of greater than 0.20, as measured on a spot sample of urine and serum, is also highly suggestive of the presence of this condition, but its absence, by no means, excludes the diagnosis. With these simple laboratory tests, possibly an earlier diagnosis can be made, and timely operation can be an entirely intestine-saving procedure.

Acute Kidney Injury↗
PubMed1978

Parathyroid cysts: report of a case with ultrastructural observations.

Parathyroid cysts are an uncommon cause of neck masses which are of uncertain origin. Electron microscopic observations reveal the cysts to be lined by a simple absorptive rather than secretory cell, which rests on a basement membrane. These are not cheif cells. Smooth muscle forms an integral part of the cyst wall. These findings of simple epithelial cells and mesenchymal tissue (smooth muscle) support the concept that these cysts represent persistent embryological remnants. A likely source is the third pharyngeal pouch.

Adult↗
PubMedDate not supplied

Nephrogenic adenoma of the urinary bladder. Histologic and cytologic observations in a case.

The histologic and cytologic features of multiple tissue and voided urine specimens from a man with nephrogenic adenoma of the urinary bladder are described. The urinary cytology showed papillary fragments, with cells showing palisade formation. The cells were round to oval, with a centrally placed nucleus with a fine chromatin pattern. These cells were identical to those seen in a low-grade papillary transitional-cell carcinoma. Tissue biopsy is needed to separate these two very different pathologic conditions.

Adenoma↗