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A Montag

Publications and source records attributed to A Montag.

At least 19 recordsLinked to original sources
PubMed1999

[Stage 3 syphilis of the mouth cavity].

BACKGROUND: Untreated syphilis or lues is a chronic infectious disease. It is caused by treponema pallidum, which is most commonly transmitted by sexual contact and occasionally by blood transfusion or by intrauterine infection. If the disorder is not treated, its clinical course can be chronic, persisting for decades. During this time, a variety of morphological signs occur depending on the stage of the disease. CASE REPORT: We describe a case of tertiary syphilis in the oropharynx with a defect of the soft palate. In a 37-year-old woman, the first symptom was a dryness of the throat followed by a feeling of foreign body in the palate area. The patient had a history of sexual contact with a man who had had syphilis ten years ago, and our initial suspicion was confirmed by a final diagnosis of tertiary syphilis. Signs of primary or secondary syphilis were not observed. RESULTS: In the course of diagnostic procedures both further manifestatons of syphilis and other infectious or malignant causes were excluded. The serological results showed a typical constellation of Treponema and non-Treponema serum reactions. The histopathological examination of an exploratory excision from the soft palate showed granulomatous changes with peripheral participation of plasma cells. We initiated appropriate antibiotic therapy, using clemizole penicillin G over a period of 21 days, which induced healing of the soft palate. CONCLUSIONS: A defect of the soft palate was diagnosed as a very rare sign of tertiary syphilis.

Adult↗
PubMed1998

K-ras oncogene mutations in osteoclast-like giant cell tumors of the pancreas and liver: genetic evidence to support origin from the duct epithelium.

Osteoclast-like giant cell tumors (OCGTs) of the pancreas and liver are enigmatic tumors. Despite their striking morphologic resemblance to certain mesenchymal tumors of bone and tendon sheath, it has been suggested that these tumors may, in fact, arise from epithelial precursors. It is also unclear whether the osteoclast-like giant cells in OCGTs are neoplastic or nonneoplastic. We identified OCGTs of the pancreas and liver that were associated with atypical intraductal epithelial proliferations or mucinous cystic neoplasms. To determine the relationship between the noninvasive epithelial proliferations and the infiltrating OCGTs, each individual component was analyzed for mutations at codon 12 of the K-ras oncogene. Four of the five-duct epithelial lesions harbored activating mutations of the K-ras oncogene. In each case, the same K-ras mutation was also present in the mononuclear cells from the paired OCGT. Moreover, these same mutations were detected when the osteoclast-like giant cells were individually microdissected and analyzed. A panel of immunohistochemical stains was performed, and the osteoclast-like giant cells demonstrated macrophage differentiation. These cells were consistently reactive for the monocyte/macrophage marker KP1, but showed absent staining for a panel of epithelial markers. The infiltrating mononuclear cells lacked strong staining for epithelial markers and monocyte/macrophage markers. These findings suggest that OCGTs of the pancreas and liver are undifferentiated carcinomas that arise directly from intraductal epithelial precursors. The finding of K-ras mutations in the osteoclast-like giant cells may reflect their propensity to phagocytize tumor cells.

Antigens, CD↗
PubMed1997

Chromosome 8 Losses in Colorectal Carcinoma: Localization and Correlation With Invasive Disease.

Background: Allelic losses from the short arm of chromosome 8 (8p) are frequent in a variety of epithelial malignancies. In colorectal cancer, there are two discrete regions of 8p loss of hterozygosity (LOH), suggesting the existence of two putative tumor suppressor genes. Previous studies have shown an association of 8p LOH with tumor invasiveness. To better define the deletion extent and the clinical significance of these losses, a series of 41 colorectal cancers were examined for 8p LOH and correlated with clinical features. Methods and Results: Paired normal and enriched tumor DNA from the same individual was typed by polymerase chain reaction for 11 microsatellite polymorphisms and scored as positive or negative for 8p LOH. Loss of 8p markers was observed in 44% of the cases. Most cases had large deletions, but several had localized interstitial losses, enabling specification of two nonoverlapping regions of LOH. The telomeric region of loss is defined by the markers D8S262 and D8S133 at 8p22, and the centromeric region is proximal to NEFL. Clinical, histopathologic, and molecular data were obtained and a significant correlation of 8p LOH with microinvasion (invasion of lymphatics, vessels, or perineurium, ascertained by light microscopy) (P=.01) and also with loss of chromosome arm 18q (P=.001) was found. Conclusions: An association of 8p allelic loss with poor outcome was demonstrated. The correlation between 8p loss and 18q loss suggests that 8p LOH is a late event in the multistep model of colorectal carcinogenesis. 8p LOH may provide a clinically useful prognostic marker in colorectal cancer, thereby warranting further testing. The involvement of two independent loci on 8p is confirmed, and the refined localization of these sites will contribute to the eventual identification of these genes, which appear to play an important role in the progression of epithelial malignancies.

Journal Article↗
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↗
PubMed1996

Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival.

Recent studies have shown that p53 mutations are frequently found in cancer of the head and neck, whereas others have indicated that human papilloma virus (HPV) infection may be involved. Thus far, no studies have examined both p53 and HPV in the same patient population and correlated the results with clinical characteristics and outcome. The purpose of this study was to examine any interrelationship between p53 and HPV in patients with squamous cell carcinoma (SCC) of the head and neck. We also planned to correlate the experimental findings with clinical characteristics, known risk factors, and treatment outcome to determine whether any prognostic factors could be detected. Archival material from 66 patients with SCC of the head and neck were selected for study based on the availability of tissue from the primary tumors prior to treatment. A data base was constructed containing all clinical parameters at the time of diagnosis and risk factors. Genomic DNA was isolated and amplified using PCR, followed by SSCP analysis and direct genomic sequencing of all variants to detect p53 mutations. Two independent methods were used for HPV detection: (a) PCR amplification using primers homologous to the E6 region of HPV 16, 18, and 33, followed by RFLP analysis; and (b) PCR amplification with HPV L1 consensus primers, followed by triple restriction enzyme digestion. The results were entered into the data base for statistical analysis. Twenty-four percent of patients were found to have p53 mutations, and 18% were positive for HPV infection. Only one patient was positive for both. Tonsilar cancer was strongly correlated with HPV (P = 0.0001) and inversely correlated with p53 (P = 0.03). The only clinical parameter associated with p53 mutation was a trend toward a heavier smoking history. A subset analysis of the patients with tonsilar cancer revealed inverse correlations with smoking (P = 0. 015) and alcohol use (P = 0.05). Also, white patients with SCC of the tonsil were more likely to be HPV positive (P = 0.015). No significant relationships with outcome were detected with either p53 or HPV in the entire population. A subset analysis of patients with stage IV disease revealed that HPV infection was correlated with overall survival. This is the largest study to date to examine both p53 and HPV in patients with SCC of the head and neck. Our results suggest that HPV may be involved in the development of these cancers in patients without traditional risk factors and that HPV-related cancers are more prevalent in the white race.

Adult↗
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↗