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Biomedical subjects

A Montag

Publications and source records attributed to A Montag.

At least 19 recordsLinked to original sources
PubMed1996

Circular sampling: perspective of a time-saving scanning procedure.

A time-saving pulse sequence that requires relatively low gradients and slow rise time is suggested herein. With this pulse sequence the entire k domain is sampled along a set of concentric circles using only 50% of the number of pulses required by the standard line sampling technique (2DFT). This can result in saving about half the total scanning time in gated cardiac imaging. The sampling configuration in the k domain is identical to MR projection reconstruction, with the advantage that a considerably smaller number of excitations is required. Furthermore, computer simulations indicate that the proposed method is also advantageous over the "half-Fourier" method, as it provides better SNR for equal acquisition time (0.83 vs. 0.707 of the 2DFT SNR respectively.

Computer Simulation↗
PubMed1996

Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors.

We performed a prospective study of sixty-two patients who were managed with a closed core needle biopsy in an outpatient clinic for a soft-tissue mass or a bone tumor with soft-tissue extension between August 1, 1992, and June 1, 1994. Eight (13 percent) of the closed core needle biopsies yielded no neoplastic tissue. Two needle biopsies (3 percent), which were of myxomatous masses, did not allow distinction between a benign and a malignant neoplasm; both masses were extraskeletal myxoid chondrosarcomas. Additionally, the histological grade of four resected specimens (6 percent) differed from that determined with the closed needle biopsy. The diagnostic accuracy of the closed needle biopsies was 84 percent (fifty-two of sixty-two). All ten diagnostic errors involved soft-tissue tumors. A retrospective study of a similar cohort of patients who had open biopsy in an outpatient operating room by the same surgeon in a contemporary period in the same institution and with analysis by the same pathologist, revealed a diagnostic accuracy of 96 percent (forty-eight of fifty). The hospital charges for the closed core needle biopsy were $1106, compared with $7234 for the open biopsy. We concluded that core needle biopsy can be performed in an outpatient clinic with use of local anesthesia and that it is substantially less expensive and more convenient than open biopsy. This technique has an acceptable but definitely lower rate of accuracy compared with open biopsy, especially for soft-tissue tumors, and it should be used only in a small subset of patients (those who have a large soft-tissue mass or a bone tumor with palpable soft-tissue extension). However, given the small size of the tissue sample, the clinician must recognize possible disadvantages, including a non-diagnostic biopsy, an indeterminate biopsy, or a potential error in the histological grade. These problems are much more likely to occur after core needle biopsy of soft-tissue masses. Because of the potential for errors in diagnosis when core needle biopsy is used, the musculoskeletal oncologist must rely on his or her clinical acumen. When a diagnosis is in reasonable doubt, there is no radiographic confirmation, the biopsy shows no tumor cells, or there is a combination of these findings, operative decisions should be made as if no biopsy had been performed. The management of patients who, after core needle biopsy, have a diagnosis of a bone or soft-tissue tumor, is best carried out by an experienced musculoskeletal oncologist working in close collaboration with an experienced musculoskeletal pathologist.

Ambulatory Care↗
PubMed1995

Chromosome 17p allelic loss in colorectal carcinoma. Clinical significance.

OBJECTIVE: To correlate allelic losses on chromosomes 5q, 8p, 17p, and 18q in colorectal adenocarcinomas with histopathologic features of known prognostic significance. DESIGN: DNA was extracted from paired samples of 56 fresh-frozen colorectal adenocarcinomas (one classified as Dukes' stage A, 22 as Dukes' stage B, 27 as Dukes' stage C, and six as Dukes'stage D) and adjacent normal mucosa. SETTING: Specimens were resected at the University of Chicago (Ill) and the University of Padova (Italy) in 1991. PATIENTS: Samples were obtained from consecutive patients. INTERVENTIONS: Chromosomes 5q, 8p, 17p, and 18q were studied for loss of heterozygosity by means of Southern hybridization blot analysis of restriction fragment length polymorphisms, and the results were correlated with pathologic tumor stage, degree of differentiation, and lymphatic and/or vascular microinvasion. RESULTS: Chromosomes 17p and 18q exhibited the highest frequency of loss of heterozygosity (40.6% and 48.8%, respectively). Most of the allelic losses were found in advanced tumors (60% in Dukes' stages C and D combined). A statistically significant correlation was found between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion (P < .01, Fisher's Exact Test). CONCLUSIONS: There was a significant correlation between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion in colorectal adenocarcinoma, a known stage-independent negative prognostic risk factor. Detection of loss of heterozygosity on chromosome 17p may identify a group of patients who may benefit from more aggressive surgical and/or early adjuvant therapy.

Alleles↗
PubMed1994

Inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islet cells with anti-ICAM-1 antibodies.

Cognate recognition of antigen-presenting cells by antigen-specific T cells is critically dependent on non-cognate adhesive interactions. For instance, several studies have shown that in vivo anti-LFA-1 plus anti-ICAM-1 mAb treatment results in prolongation of allograft survival. We have developed a xenogeneic islet transplant model to investigate the role of various adhesion interactions in the xenogeneic response and study the effect of pretreating donor tissue with immunosuppressive drugs. Pancreatic islet cells were pretreated in vitro with anti-human ICAM-1 mAb, transplanted under the renal capsule of diabetic B6 mice in the absence of systemic immunosuppression and examined for long-term xenograft acceptance. The survival of human islets pretreated with anti-human ICAM-1 was significantly prolonged (MST = 53 days, with 40% of grafts surviving > 100 days). In contrast, the survival of human islets pretreated with the control antibody was similar to those of nontreated islets (MST = 7 days). A massive lymphocyte infiltrate into control xenografts was observed at 5 days post-transplant. In contrast, a lymphocyte infiltrate did not appear in the anti-ICAM-1-treated islets for at least 11 days. Only mAbs specific for the LFA-1 binding epitope of ICAM-1 were found to inhibit a mixed islet/lymphocyte reaction in vitro and block graft rejection in vivo. However, graft prolongation is not accompanied by systemic tolerance. Mice transplanted simultaneously with human islet cells treated with control Ig (left kidney) or anti-ICAM-1 (right kidney) rejected the control islets but not anti-ICAM-1-treated islets. These results suggest that the LFA-1/ICAM-1 interaction is a critical component for xenograft rejection and, more important, that pretreatment of islet tissue with anti-adhesion molecule antibodies can profoundly alter graft recognition and rejection in the absence of any systemic drug therapy. However, graft prolongation is not accompanied by systemic tolerance induction.

Animals↗
PubMed1994

Protective effect of an adenosine kinase inhibitor in septic shock.

Adenosine exhibits potent anti-inflammatory activities but its therapeutic use is limited by cardiovascular side effects. Inhibitors of an enzyme involved in adenosine metabolism, adenosine kinase (EC 2.7.1.20), were evaluated for their ability to enhance endogenous adenosine production. One novel adenosine kinase inhibitor, GP-1-515, was studied in two models of septic shock to assess its protective effects. GP-1-515 significantly decreased mortality in mice that received a lethal i.v. injection of endotoxin. The beneficial effect was accompanied by decreased neutrophil accumulation in the lungs and was reversed by an adenosine receptor antagonist, implying that the effects were mediated by endogenous adenosine. Plasma levels of TNF-alpha, but not IL-1 alpha or IL-6, were lower in the GP-1-515-treated animals. In a second model of sepsis, GP-1-515 increased survival in bacterial peritonitis in rats. The mechanism of action in both models was likely multifactorial, including adenosine-mediated inhibition of neutrophil adhesion, cytokine production, and oxygen radical generation. Adenosine kinase inhibitors have potent anti-inflammatory effects in vitro and in vivo and represent a novel therapeutic approach to the treatment of inflammatory diseases.

Adenosine↗
PubMed1994

Loss of heterozygosity in 8p is associated with microinvasion in colorectal carcinoma.

Loss of heterozygosity (LOH) from the short arm of chromosome 8 is frequent in a variety of malignancies, suggesting the presence of a tumor suppressor gene in this region. Previous studies suggested that this deletion may correlate with higher clinicopathologic stages in colorectal cancer, but others did not support this finding; in part, this difficulty is due to the low heterozygosity of the RFLP markers that were used. Here we report on a preliminary investigation in which we used highly informative microsatellite markers to determine whether deletions of 8p are correlated with poor prognostic features. Paraffin-embedded tumor tissue from 15 patients was analyzed with a panel of three microsatellite markers that are known to be sites of frequent LOH. Fourteen of the 15 cases were informative with at least one marker, and 7 showed LOH. Analysis of clinical features showed that there was no relation of 8p LOH with patient age or tumor stage, grade, location, or pattern of growth. However, a statistically significant correlation was seen between LOH and lymphatic, vascular, or perineural microinvasion (Fisher exact test, P = 0.01). This histologic feature is known to be a stage-independent indicator of prognosis. Our data suggest that 8p LOH may be associated with poor outcome and demonstrate the utility of these microsatellite markers for its detection.

Adenocarcinoma↗
PubMed1994

Histologic pathology of the liver in progressive familial intrahepatic cholestasis.

This work details the histologic findings in 84 liver biopsy specimens from 28 patients with progressive familial intrahepatic cholestasis (PFIC), who met the clinical criteria of early onset of chronic unremitting cholestasis, exclusion of any known metabolic or anatomic etiology, and low serum gamma-glutamyl transpeptidase (GGTP) values. Hepato-canalicular cholestasis and disruption of the liver cell plate arrangement were early, uniform findings, and giant cell transformation was found in 56% of initial biopsies. Duct loss was a prominent finding; 70% of patients had ductal paucity, and many had abnormal bile duct epithelium, suggesting degeneration. Fibrosis was seen in the samples from 16 patients, including bridging fibrosis in specimens obtained from six patients during the first 2 years of life. Proliferating ductules at the margins of portal tracts increased as fibrosis progressed and were especially prominent in end-stage histology. Cirrhosis developed in nine of these patients and had a characteristic histologic pattern, consisting of biliary cirrhosis with diffuse stellate lobular fibrosis associated with severe cholestasis and pseudoacinar transformation. Mallory hyalin and hepatocellular carcinoma were observed in materials from some patients with advanced cirrhosis. The constellation of histologic findings in PFIC forms a recognizable pattern, and the liver histology appears to have a predictable progression.

Adolescent↗
PubMed1994

Adenosine-mediated inhibition of platelet aggregation by acadesine. A novel antithrombotic mechanism in vitro and in vivo.

Inhibition of platelet aggregation by acadesine was evaluated both in vitro and ex vivo in human whole blood using impedance aggregometry, as well as in vivo in a canine model of platelet-dependent cyclic coronary flow reductions. In vitro, incubation of acadesine in whole blood inhibited ADP-induced platelet aggregation by 50% at 240 +/- 60 microM. Inhibition of platelet aggregation was time dependent and was prevented by the adenosine kinase inhibitor, 5'-deoxy 5-iodotubercidin, which blocked conversion of acadesine to its 5'-monophosphate, ZMP, and by adenosine deaminase. Acadesine elevated platelet cAMP in whole blood, which was also prevented by adenosine deaminase. In contrast, acadesine had no effect on ADP-induced platelet aggregation or platelet cAMP levels in platelet-rich plasma, but inhibition of aggregation was restored when isolated erythrocytes were incubated with acadesine before reconstitution with platelet-rich plasma. Acadesine (100 mg/kg i.v.) administered to human subjects also inhibited platelet aggregation ex vivo in whole blood. In the canine Folts model of platelet thrombosis, acadesine (0.5 mg/kg per min, i.v.) abolished coronary flow reductions, and this activity was prevented by pretreatment with the adenosine receptor antagonist, 8-sulphophenyltheophylline. These results demonstrate that acadesine exhibits antiplatelet activity in vitro, ex vivo, and in vivo through an adenosine-dependent mechanism. Moreover, the in vitro studies indicate that inhibition of platelet aggregation requires the presence of erythrocytes and metabolism of acadesine to acadesine monophosphate (ZMP).

Adenosine↗
PubMed1994

A comparison of the prognoses for deep and subcutaneous sarcomas of the extremities.

We evaluated 172 patients who had a soft-tissue sarcoma of the extremity in order to determine whether the prognosis for a subcutaneous sarcoma was better than that for a deep sarcoma. At a median of thirty-six months after the biopsy or definitive operation at our hospital, six of the fifty-two patients who had had a subcutaneous sarcoma had died and one had had a local recurrence; in contrast, forty of the 120 patients who had had a deep sarcoma had died and eight had had a local recurrence. Twenty-five (48 percent) of the subcutaneous sarcomas were malignant fibrous histiocytomas, and thirty-eight (73 percent) were small (five centimeters or less in the largest dimension). The three-year estimates of disease-free survival were 85 percent for the patients who had a subcutaneous sarcoma and 54 per cent for those who had a deep sarcoma (p = 0.002). Although the survival estimates remained significantly different when the groups were matched for histological diagnosis and for intracompartmental location (p = 0.0001 and 0.0006, respectively), they were not significantly different when the groups were matched for the size of the tumor (p = 0.42). A Cox proportional-hazards model confirmed that a tumor size of more than five centimeters and the histological grade are the most significant prognostic factors (p = 0.0007 and p = 0.004, respectively): a tumor size of more than five centimeters was associated with a relative risk of 3.5 (95 per cent confidence interval, 1.7 to 7.3), and a higher histological grade was associated with a relative risk of 4.0 (95 per cent confidence interval, 1.6 to 10.3). Subcutaneous location, when considered separately, was not a significant prognostic factor (p = 0.45). The data indicate that a tumor size of more than five centimeters is a more important prognostic indicator than histological diagnosis, depth, or intracompartmental location.

Adolescent↗
PubMed1993

Comparison of mutations of ras oncogene in human pancreatic exocrine and endocrine tumors.

BACKGROUND: Ras oncogene mutations have been found in many human cancers; however, pancreatic endocrine tumors have rarely been studied. The purpose of this study was to analyze ras mutations in pancreatic endocrine tumors and to compare these results with the incidence of ras mutations in pancreatic exocrine cancers studied in our laboratory. METHODS: Ras oncogene mutations were studied in 33 foregut endocrine tumors (pancreatic 31, duodenal submucosa 2). Eleven were insulinomas, 12 gastrinomas, 2 glucagonomas, and 11 others were nonfunctioning islet cell carcinomas. Thirteen were benign and 20 were malignant. These were compared with 65 pancreatic exocrine cancers. Tumors were microdissected from paraffin-embedded sections. DNA was extracted and amplified by polymerase chain reaction. Mutations were detected by a oligonucleotide hybridization method with sequence-specific phosphorus 32-radiolabeled probes. RESULTS: No ras mutations were identified among the 33 pancreatic endocrine tumors. In contrast, 51 of 65 (78.5%) pancreatic exocrine cancers exhibited a ras mutation. Fifty were K-ras mutations and one unusual tumor exhibited a N-61 ras mutation. CONCLUSIONS: Ras oncogene mutations do not play a role in the tumorigenesis of pancreatic endocrine tumors.

Adenoma, Islet Cell↗
PubMed1993

Tissue and cell-specific patterns of expression of rat liver and intestinal fatty acid binding protein during development and in experimental colonic and small intestinal adenocarcinomas.

BACKGROUND: Mammalian small intestinal and colonic epithelium express members of a multigene family of hydrophobic ligand binding proteins of which liver and intestinal fatty acid binding protein represent among the most abundant intestinal gene products. These proteins are expressed in a cell- and region-specific manner and emerge in a temporally distinctive pattern. EXPERIMENTAL DESIGN: We have studied expression of these genes in the small intestine and colon of rats treated with 1,2-dimethylhydrazine since these animals develop a predictable pattern of both small and large bowel cancers. Studies were also undertaken in fetal and neonatal small intestine and colon. RESULTS: There was a 10- and 50-fold decrease, respectively, in mRNA abundance for intestinal and liver fatty acid binding protein in RNA from colon cancers compared with either uninvolved or control RNA. Immunocytochemical analysis revealed decreased staining for both proteins within their normal distribution together with ectopic clusters of cells reactive for liver fatty acid binding protein within colonic tumors. A more striking mosaic of immunocytochemical staining for both liver and intestinal fatty acid binding protein was found in small intestinal adenocarcinomas. Similar mosaic patterns of immunocytochemical staining were transiently detectable in rat fetal small intestine and neonatal colon. CONCLUSIONS: The region- and cell-specific expression of these genes, which may be linked temporally to events in intestinal differentiation, are subject to disruption in a cell-specific manner in the transformed, or dedifferentiated, phenotype.

1,2-Dimethylhydrazine↗
PubMed1992

Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer.

Little is known regarding the molecular genetic events in head and neck carcinoma. Epidemiological evidence suggests that both alcohol and tobacco use are related to the development of these neoplasms, and viral infections have also been postulated to play a role in some tumors. Loss of p53 tumor suppressor gene function has been found in many malignancies and can occur through either gene mutation or by interaction with the E6 protein of oncogenic human papilloma viruses (HPV). Because the mucosal surfaces of the head and neck are exposed to mutagens and HPVs, we studied DNA derived from 30 stage I-IV squamous cell carcinomas of the head and neck (9 primary tumors and 21 early passage cell lines) for p53 gene mutations as well as for the presence of oncogenic HPV DNA. Exons 2 through 11 of the p53 gene were examined using single strand conformation polymorphism analysis followed by direct genomic sequencing of all variants. HPV detection was done using polymerase chain reaction amplification with HPV E6 region type specific primers as well as L1 region degenerate ("consensus") primers; HPV type was determined by restriction fragment length polymorphism analysis of the amplified fragment as well as by Southern blotting of genomic DNA. Sixteen of 30 tumors (53%) had p53 mutations and oncogenic HPV DNA was detected in 3 of 30 (10%) tumors, none of which had p53 mutations. The p53 mutational spectrum observed was characterized by equal frequencies of transversions (6 of 16), transitions (5 of 16), and deletions (5 of 16). This distribution of mutations differs from the spectrum of p53 mutation reported in esophageal (P = 0.05) and lung (P = 0.02) cancers, two other tobacco associated neoplasms. A previously undescribed clustering of 3 mutations at codon 205 was also observed. A trend toward a shorter time to tumor recurrence after treatment was noted for those patients with tumors exhibiting p53 gene mutations, and no relationship between p53 mutations and tumor stage or node status was noted. Alteration in p53 gene function appears common in head and neck cancer, and the mutational spectrum observed may reflect the role of different mutagens or mutagenic processes than those responsible for the p53 mutations in lung and esophageal neoplasms.

Alcohol Drinking↗
PubMed1992

Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg.

Antigen-specific T cell activation depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules bind to their ligands, such as CD28 to the B7 (also called BB1) molecule. A soluble fusion protein of human CTLA-4 (a protein homologous to CD28) and the immunoglobulin (lg) G1 Fc region (CTLA4lg) binds to human and murine B7 with high avidity and blocks T cell activation in vitro. CTLA4lg therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7+ antigen-presenting cells. In addition, CTLA4lg induced long-term, donor-specific tolerance, which may have applications to human organ transplantation.

Abatacept↗