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Biomedical subjects

N P Zauber

Publications and source records attributed to N P Zauber.

At least 19 recordsLinked to original sources
PubMed2004

Ki-ras gene mutations, LOH of the APC and DCC genes, and microsatellite instability in primary colorectal carcinoma are not associated with micrometastases in pericolonic lymph nodes or with patients' survival.

AIMS: The primary aim of this study was to look for possible correlations between molecular genetic changes in primary colorectal cancer and the presence or absence of micrometastases in the accompanying pericolonic lymph nodes. The secondary aim was to correlate the data on these molecular genetic changes and micrometastases with survival. METHODS: One hundred and twenty five Dukes's stage B colorectal cancers from 1989 to 1992 were analysed. The primary tumours were evaluated for Ki-ras mutation, adenomatous polyposis coli (APC) loss of heterozygosity (LOH), deleted in colon cancer (DCC) LOH, and microsatellite instability using standard molecular techniques. All available lymph nodes were immunohistochemically stained for micrometastases. RESULTS: Micrometastases were present in 41% of patients. There were significantly more lymph nodes removed in the patients with micrometastases. Micrometastases were not associated with Ki-ras mutation, APC LOH, DCC LOH, or microsatellite instability, even when controlling for the number of lymph nodes removed. None of the molecular variables considered had a significant impact on either overall survival or on death with disease. CONCLUSIONS: There are insufficient data to justify using molecular genetic changes in primary colorectal carcinomas as prognostic markers. Micrometastases do not provide prognostic information on survival. There is value in increasing the numbers of lymph nodes removed and analysed along with the primary tumour.

Aged↗
PubMed2001

Molecular changes in the Ki-ras and APC genes in colorectal adenomas and carcinomas arising in the same patient.

The purpose of this study was to compare the molecular genetic changes in the Ki-ras and adenomatous polyposis coli (APC) genes between adenomas and carcinomas removed from the same patients. This comparison of benign and malignant tissue would enhance understanding of the progression of molecular changes during the development of colorectal malignancy and similarities between paired lesions could be indicative of a common aetiology. The basic procedures used were DNA extraction from wax blocks of removed tissue, followed by polymerase chain reaction (PCR) and gel electrophoresis for mutations in the Ki-ras gene using single strand conformational polymorphism (SSCP); amplification of a CA repeat marker was used to assess for loss of heterozygosity (LOH) of the APC gene. The main findings in 100 adenoma and carcinoma pairs for the Ki-ras gene were as follows: the frequency of Ki-ras mutation in the adenomas increased with increasing villous component, but did not vary in the paired carcinomas; the frequency of Ki-ras mutation in villous adenomas was greater than in carcinomas; and when both paired lesions had Ki-ras mutations, only 44% had the identical mutation. For the APC gene, the incidence of LOH in the adenomas did not vary by histological type; the LOH status of the adenoma was associated with that of the paired carcinoma; but when both paired lesions had LOH of the APC gene, only 50% had LOH for the same allele. In conclusion, these data on paired adenomas and carcinomas suggest that a Ki-ras mutation is not a consistent finding between the adenoma and carcinoma from the same bowel. The development of LOH of the APC gene is a slightly more consistent finding between the pair, but is not always allelic-specific.

Adenoma↗
PubMed2000

Effect of cholesterol levels on villous histology in colonic adenomas.

To date no studies have examined the relationship between cholesterol levels and the occurrence of specific colonic polyp histologies. Villous histology has a greater predilection for subsequent malignancies than other histologies. Consequently, we examined the effect of cholesterol levels on the occurrence of villous adenomas. Just under one in 10 (9.5%, 15/158) patients had polyps with villous histologies. Cholesterol levels were positively and nonlinearly associated with a greater likelihood of villous histology, suggesting that a threshold exists for the effect of cholesterol level on the likelihood of having polyps with villous histology [odds ratios (OR) for combined two variable quadratic effect: cholesterol OR, 1.18; 95% confidence interval (CI), 1.02-1.37 and cholesterol squared OR, 1.004; 95% CI, 1.00-1.02]. Our data suggest that, in patients with polyps, higher cholesterol levels increase the likelihood of having polyps with villous histology, but that the effect of cholesterol level reaches a threshold.

Adenoma, Villous↗
PubMed1999

K-ras mutation and loss of heterozygosity of the adenomatous polyposis coli gene in patients with colorectal adenomas with in situ carcinoma.

BACKGROUND: The majority of colorectal carcinomas, if not all, arise from a benign adenoma. The DNA of the carcinomatous cells frequently has mutations in several genes. However, it is not exactly clear when during the neoplastic process each mutation develops. An adenoma with an area of in situ carcinoma provides an opportunity to evaluate genetic changes within a single neoplasia whose separate areas are comprised of both the benign adenoma as well as the malignant carcinoma. METHODS: Thirty-seven neoplasms with areas of both benign adenoma and in situ carcinoma were studied. Both portions were evaluated for loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene and for mutations in codons 12/13 of the K-ras oncogene using the polymerase chain reaction technique. RESULTS: Twenty-eight neoplasms showed no LOH in either portion whereas both portions of 4 neoplasms revealed a loss of heterozygosity. In three lesions the APC gene was normal in the adenomatous portion but LOH was present in the carcinomatous portion. Two neoplasms were uninformative for LOH of the APC gene. Thirteen neoplasms showed the wild-type pattern for the K-ras oncogene whereas 15 contained the identical mutation in both portions. Of the remaining nine neoplasms, six had a K-ras mutation in the adenomatous portion only and three had one pattern in the adenomatous portion and a different pattern in the in situ carcinoma portion. CONCLUSIONS: LOH of the APC gene is an early and persistent feature in the evolution of a benign colorectal adenoma into an in situ carcinoma. There is less consistency regarding K-ras mutations; one in five in situ carcinomas contains a K-ras mutation different from that observed in the adenomatous portion.

Adenomatous Polyposis Coli↗
PubMed1999

Comparison of allelic ratios from paired blood and paraffin-embedded normal tissue for use in a polymerase chain reaction to assess loss of heterozygosity.

BACKGROUND: One method to assess loss of heterozygosity (LOH) of various genes is the amplification of DNA from neoplastic tissue by using microsatellite markers. LOH can best be considered on a quantitative basis as a comparison of allelic ratios of neoplastic tissue to that of the normal control. We will illustrate through quantitative methods the importance of using the appropriate controls when determining allelic loss. METHODS AND RESULTS: DNA extracted from 28 paired blood and formalin-fixed, paraffin-embedded normal mucosal tissue was amplified using the DP1 microsatellite marker, consisting of a variable number of CA repeats. This marker is located within the D5S346 (DP1) region on chromosome 5 and is linked to the adenomatous polyposis coli gene. Allelic ratios were calculated after scanning autoradiographs on a densitometer. Ratio values approaching 1 were observed when the two alleles were close in molecular weight, whereas ratios less than 1 were detected when the two alleles had very different molecular weights. This discrepancy was more pronounced in paraffin-embedded tissue than with blood samples. CONCLUSION: For LOH amplification assays, it is best to use normal control samples that are of the same tissue source as the neoplastic sample being analyzed. When assessing LOH in neoplastic tissue, a quantitative value rather than visual assessment of the alleles should be considered. The values may be normalized by dividing the ratio of the two tumor alleles by the ratio of the two normal alleles.

Alleles↗
PubMed1998

Enteropathy-associated T cell lymphoma with brain involvement.

In a patient with enteropathy-associated T cell lymphoma. there was dissemination to the brain manifesting as an inflammatory lesion. the intestinal and brain lesions were studied using routine histology, immunohistochemistry, and polymerase chain reaction. The jejunum was involved by a multifocal large cell lymphoma associated with multiple inflammatory ulcers and villous atrophy with crypt hyperplasia of the intervening mucosa. The lesion in the brain consisted of necrotic tissue associated with an infiltrate of histiocytes and a relatively scant infiltrate of primarily small lymphocytes. The appearance was that of an inflammatory rather than a neoplastic process. The intestinal lymphoma cells were positive for T cell markers and contained cytotoxic granules detected with the TIA-1 monoclonal antibody. The small lymphocytes and occasional large cells in the cerebral lesion showed the same immunophenotype. DNA extracted from the intestinal lymphoma and the cerebral lesion showed identical monoclonal rearrangement of the TCR-gamma gene. Dissemination from enteropathy-associated T cell lymphoma may masquerade as an inflammatory lesion. Molecular analysis is useful in confirming the diagnosis.

Aged↗
PubMed1998

Factor V Leiden mutation is not increased in patients with inflammatory bowel disease.

Individuals with inflammatory bowel disease (IBD) are known to have an increased incidence of thromboembolic disease. Activated protein C resistance (APCR) has been identified as one of several inherited disorders of coagulation that predispose individuals to thromboembolic problems. This resistance results from a single point mutation in the factor V gene, called factor V Leiden. It has been suggested that many patients with IBD have APCR, as tested by a clotting assay. We have evaluated a series of 49 patients with IBD, none of whom had a history of thromboembolic disease. We assayed for the factor V Leiden mutation by polymerase chain reaction and found only one heterozygote. Seventeen of the 49 patients were negative for APCR by the clotting assay. Factor V Leiden mutation is not more common in patients with IBD than in the general population. We were unable to confirm a prior report indicating that patients with IBD have a higher prevalence of resistance to activated protein C.

Activated Protein C Resistance↗
PubMed1995

Myeloproliferative disorders in two New Jersey families.

Two New Jersey families were diagnosed with myeloproliferative disorders. Each family had an associated disorder: beta-thalassemia and lung carcinoma. In both families, neoplasia in the second generation was diagnosed at an earlier age than in the predecessors.

Adenocarcinoma↗
PubMed1987

Hematologic data of healthy very old people.

Hematologic values were analyzed for 44 people who were 84 years of age or older. Individuals were selected based on extensive long-term records confirming their excellent health. Mean hemoglobin values were 14.8 +/- 1.1 g/dL (148 +/- 11 g/L) for men and 13.6 +/- 1.0 g/dL (136 +/- 10 g/L) for women. Mean values were also computed for red blood cell indexes, red and white blood cell counts, sedimentation rate, and serum iron, and all values were compared with those of a concurrent control group of healthy young adults. Results are discussed in the context of previous reports on hematologic data of the elderly.

Adult↗
PubMed1982

Giant cell arteritis and microangiopathic hemolytic anemia.

Microangiopathic hemolytic anemia was found in a 67 year old woman with biopsy-proven giant cell arteritis. The patient's symptoms, as well as the hemolytic process, were suppressed by high-dose steroid therapy on several occasions. The presence of microangiopathic hemolytic anemia is consistent with the concept that erythrocyte fragmentation resulted from contract with intravascular fibrin. This is the first, reported case of microangiopathic hemolytic anemia with temporal arteritis.

Aged↗
PubMed1977

Factor IX levels in patients with hemophilia B (Christmas disease) following transfusion with concentrates of factor IX or fresh frozen plasma (FFP).

There has been no systematic re-examination of variables that may affect the level and duration of response of patients with hemophilia B (Christmas disease) to transfusion. Therefore, 49 of our transfusion episodes and 171 previously reported transfusions were evaluated. Mean calculated initial increase of Factor IX levels (delta %/unit (U) of procoagulant activity infused/kg) was 0.82 +/- 0.09% (mean +/-S.E.) in previously reported cases and 1.01 +/- 0.13% in our patients, after transfusion of concentrate; but only 0.05 +/- 0.11% after fresh frozen plasma (FFP). Response was not altered by acute hemorrhage, baseline Factor IX levels, or body weight. Proplex (Hyland) and Konyne (Cutter) produced similar responses. Following transfusion, the disappearance curve was biphasic. The mean T1/2 for the second component was 27.5 hrs, but the direct T1/2 was only 6.4 +/- 1.0 hr. Regardless of common clinical variables, increase of Factor IX following transfusion of American concentrates is 1.0% (or 0.01 U)/1 administered/kg. Appropriate frequency of transfusion depends upon an understanding of the biphasic disappearance of Factor IX. Importantly, the initial frequency of transfusion therapy should be based on a direct T1/2 of only 6 to 8 hrs.

Blood Transfusion↗