Peter Pharis | Southeastern Baptist Theological Seminary (original) (raw)

Papers by Peter Pharis

Research paper thumbnail of Tissue section image analysis of the breast neoplasms: Evidence of false aneuploidy

Journal of Cellular Biochemistry, 1993

Two methods have emerged for measuring the DNA content of paraffin-embedded tissue using image cy... more Two methods have emerged for measuring the DNA content of paraffin-embedded tissue using image cytometry: (1) analysis of thin sections, and (2) analysis of nuclei extracted from thick sections. These methods were evaluated using 31 breast tumors for which paraffin-embedded material was available. Cases selected represented 11 diploid, 11 tetraploid, and 9 aneuploid tumors. Results generated using image cytometry methods were compared with those obtained using flow cytometry. For thin sections, the tissue correction feature of the CAS 200 Image Cytometer was used to estimate the DNA content of whole nuclei from measurements made on sectioned nuclei. DNA histograms were generated from tissue sections cut at the same microtome setting (5 pm) before and after software corrections of 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, and 7.5 pm. A comparison of flow cytometry and thin-section image analysis in the absence of tissue correction showed 90% concordance for diploid, 27% concordance for tetraploid, and 77% concordance for aneuploid tumors. The ploidy estimated on thin sections by at least one of the correction values was discordant in 72% of diploid, 91% of tetraploid, and 78% of aneuploid tumors. For cell nuclei extracted from paraffin, excellent agreement was found between flow and image cytometry (r = 0.933). It was concluded that in most cases, cell nuclei extracted from paraffin are preferable to tissue sections for ploidy analysis of breast tumors using image cytometry.

Research paper thumbnail of Antigen Based Therapies to Prevent Diabetes in NOD Mice

Journal of Autoimmunity, 1996

Interventional approaches that have been successful in delaying insulindependent diabetes mellitu... more Interventional approaches that have been successful in delaying insulindependent diabetes mellitus (IDDM) using antigen-based immunotherapies include parenteral immunization. It has potential for clinical application provided that effective adjuvants suitable for human use can be found. We have previously shown that immunization with insulin and insulin B chain but not A chain in incomplete Freund's adjuvant (IFA) prevented diabetes by reducing IFN-mRNA in the insulitis lesions. In this paper we show that the insulin B chain peptide (p9-23) contain the most protective epitope. Immunization with selected GAD peptides was ineffective. Immunization with B chain but not A chain using alum as adjuvant delayed diabetes onset (P=0.012), whereas administration of alum alone was not protective. When Diphtheria-Tetanus toxoid-Acellular Pertussis (DTP) vaccine was used as the adjuvant vehicle, DTP itself induced significant protection (P<0.003) which was associated with a Th2-like cytokine producing insulitis profile, IL-4 driven IgG1 antibody responses to insulin, GAD in the periphery and an augmentation of the autoimmune response to GAD. The anti-diabetic effect of DTP was enhanced when given with insulin B chain. These results encourage consideration of an approach using alum/DTP and insulin B chain immunization in clinical trials.

Research paper thumbnail of Mesenchymal hamartoma of the liver. DNA flow cytometric analysis of eight cases

Cancer, 1994

Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is bel... more Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is believed to be either a developmental anomaly or reactive process. Because of recent reports of specific translocations involving chromosome 19 in mesenchymal hamartomas and certain ultrastructural and histologic features suggesting a relationship between mesenchymal hamartoma and undifferentiated (embryonal) sarcoma of the liver, some have speculated that mesenchymal hamartoma may be a neoplastic lesion with uncertain malignant potential. Because DNA aneuploidy can be useful as a marker for neoplasia, the authors decided to assess ploidy in paraffin embedded mesenchymal hamartomas using flow cytometry. The authors retrospectively examined mesenchymal hamartomas from eight children and evaluated the clinicopathologic features and the ploidy of the lesions. Boys and girls were equally affected, and the mean age at presentation was 11 months. Lesions involved predominantly the right lobe of the liver, with a range of greatest dimension of 7-25 cm, and a mean weight of 651 g (though weights for three of the largest lesions were not recorded). Flow cytometric analysis of nuclei extracted from paraffin embedded tissue revealed that six of the eight lesions were DNA diploid, whereas two were DNA aneuploid (with DNA indices of 1.13 and 1.25). All of the lesions had a low S phase fraction. The authors concluded that although most mesenchymal hamartomas are diploid, a subset of mesenchymal hamartomas is aneuploid. The finding of aneuploidy in mesenchymal hamartoma, in conjunction with the reported cytogenetic abnormalities, suggests that mesenchymal hamartoma may be a true neoplasm and not a developmental anomaly or reactive process.

Research paper thumbnail of Mesenchymal hamartoma of the liver. DNA flow cytometric analysis of eight cases

Cancer, 1994

Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is bel... more Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is believed to be either a developmental anomaly or reactive process. Because of recent reports of specific translocations involving chromosome 19 in mesenchymal hamartomas and certain ultrastructural and histologic features suggesting a relationship between mesenchymal hamartoma and undifferentiated (embryonal) sarcoma of the liver, some have speculated that mesenchymal hamartoma may be a neoplastic lesion with uncertain malignant potential. Because DNA aneuploidy can be useful as a marker for neoplasia, the authors decided to assess ploidy in paraffin embedded mesenchymal hamartomas using flow cytometry. The authors retrospectively examined mesenchymal hamartomas from eight children and evaluated the clinicopathologic features and the ploidy of the lesions. Boys and girls were equally affected, and the mean age at presentation was 11 months. Lesions involved predominantly the right lobe of the liver, with a range of greatest dimension of 7-25 cm, and a mean weight of 651 g (though weights for three of the largest lesions were not recorded). Flow cytometric analysis of nuclei extracted from paraffin embedded tissue revealed that six of the eight lesions were DNA diploid, whereas two were DNA aneuploid (with DNA indices of 1.13 and 1.25). All of the lesions had a low S phase fraction. The authors concluded that although most mesenchymal hamartomas are diploid, a subset of mesenchymal hamartomas is aneuploid. The finding of aneuploidy in mesenchymal hamartoma, in conjunction with the reported cytogenetic abnormalities, suggests that mesenchymal hamartoma may be a true neoplasm and not a developmental anomaly or reactive process.

Research paper thumbnail of Tissue section image analysis of the breast neoplasms: Evidence of false aneuploidy

Journal of Cellular Biochemistry, 1993

Two methods have emerged for measuring the DNA content of paraffin-embedded tissue using image cy... more Two methods have emerged for measuring the DNA content of paraffin-embedded tissue using image cytometry: (1) analysis of thin sections, and (2) analysis of nuclei extracted from thick sections. These methods were evaluated using 31 breast tumors for which paraffin-embedded material was available. Cases selected represented 11 diploid, 11 tetraploid, and 9 aneuploid tumors. Results generated using image cytometry methods were compared with those obtained using flow cytometry. For thin sections, the tissue correction feature of the CAS 200 Image Cytometer was used to estimate the DNA content of whole nuclei from measurements made on sectioned nuclei. DNA histograms were generated from tissue sections cut at the same microtome setting (5 pm) before and after software corrections of 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, and 7.5 pm. A comparison of flow cytometry and thin-section image analysis in the absence of tissue correction showed 90% concordance for diploid, 27% concordance for tetraploid, and 77% concordance for aneuploid tumors. The ploidy estimated on thin sections by at least one of the correction values was discordant in 72% of diploid, 91% of tetraploid, and 78% of aneuploid tumors. For cell nuclei extracted from paraffin, excellent agreement was found between flow and image cytometry (r = 0.933). It was concluded that in most cases, cell nuclei extracted from paraffin are preferable to tissue sections for ploidy analysis of breast tumors using image cytometry.

Research paper thumbnail of Antigen Based Therapies to Prevent Diabetes in NOD Mice

Journal of Autoimmunity, 1996

Interventional approaches that have been successful in delaying insulindependent diabetes mellitu... more Interventional approaches that have been successful in delaying insulindependent diabetes mellitus (IDDM) using antigen-based immunotherapies include parenteral immunization. It has potential for clinical application provided that effective adjuvants suitable for human use can be found. We have previously shown that immunization with insulin and insulin B chain but not A chain in incomplete Freund's adjuvant (IFA) prevented diabetes by reducing IFN-mRNA in the insulitis lesions. In this paper we show that the insulin B chain peptide (p9-23) contain the most protective epitope. Immunization with selected GAD peptides was ineffective. Immunization with B chain but not A chain using alum as adjuvant delayed diabetes onset (P=0.012), whereas administration of alum alone was not protective. When Diphtheria-Tetanus toxoid-Acellular Pertussis (DTP) vaccine was used as the adjuvant vehicle, DTP itself induced significant protection (P<0.003) which was associated with a Th2-like cytokine producing insulitis profile, IL-4 driven IgG1 antibody responses to insulin, GAD in the periphery and an augmentation of the autoimmune response to GAD. The anti-diabetic effect of DTP was enhanced when given with insulin B chain. These results encourage consideration of an approach using alum/DTP and insulin B chain immunization in clinical trials.

Research paper thumbnail of Mesenchymal hamartoma of the liver. DNA flow cytometric analysis of eight cases

Cancer, 1994

Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is bel... more Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is believed to be either a developmental anomaly or reactive process. Because of recent reports of specific translocations involving chromosome 19 in mesenchymal hamartomas and certain ultrastructural and histologic features suggesting a relationship between mesenchymal hamartoma and undifferentiated (embryonal) sarcoma of the liver, some have speculated that mesenchymal hamartoma may be a neoplastic lesion with uncertain malignant potential. Because DNA aneuploidy can be useful as a marker for neoplasia, the authors decided to assess ploidy in paraffin embedded mesenchymal hamartomas using flow cytometry. The authors retrospectively examined mesenchymal hamartomas from eight children and evaluated the clinicopathologic features and the ploidy of the lesions. Boys and girls were equally affected, and the mean age at presentation was 11 months. Lesions involved predominantly the right lobe of the liver, with a range of greatest dimension of 7-25 cm, and a mean weight of 651 g (though weights for three of the largest lesions were not recorded). Flow cytometric analysis of nuclei extracted from paraffin embedded tissue revealed that six of the eight lesions were DNA diploid, whereas two were DNA aneuploid (with DNA indices of 1.13 and 1.25). All of the lesions had a low S phase fraction. The authors concluded that although most mesenchymal hamartomas are diploid, a subset of mesenchymal hamartomas is aneuploid. The finding of aneuploidy in mesenchymal hamartoma, in conjunction with the reported cytogenetic abnormalities, suggests that mesenchymal hamartoma may be a true neoplasm and not a developmental anomaly or reactive process.

Research paper thumbnail of Mesenchymal hamartoma of the liver. DNA flow cytometric analysis of eight cases

Cancer, 1994

Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is bel... more Mesenchymal hamartoma of the liver is a rare lesion seen predominantly in childhood, which is believed to be either a developmental anomaly or reactive process. Because of recent reports of specific translocations involving chromosome 19 in mesenchymal hamartomas and certain ultrastructural and histologic features suggesting a relationship between mesenchymal hamartoma and undifferentiated (embryonal) sarcoma of the liver, some have speculated that mesenchymal hamartoma may be a neoplastic lesion with uncertain malignant potential. Because DNA aneuploidy can be useful as a marker for neoplasia, the authors decided to assess ploidy in paraffin embedded mesenchymal hamartomas using flow cytometry. The authors retrospectively examined mesenchymal hamartomas from eight children and evaluated the clinicopathologic features and the ploidy of the lesions. Boys and girls were equally affected, and the mean age at presentation was 11 months. Lesions involved predominantly the right lobe of the liver, with a range of greatest dimension of 7-25 cm, and a mean weight of 651 g (though weights for three of the largest lesions were not recorded). Flow cytometric analysis of nuclei extracted from paraffin embedded tissue revealed that six of the eight lesions were DNA diploid, whereas two were DNA aneuploid (with DNA indices of 1.13 and 1.25). All of the lesions had a low S phase fraction. The authors concluded that although most mesenchymal hamartomas are diploid, a subset of mesenchymal hamartomas is aneuploid. The finding of aneuploidy in mesenchymal hamartoma, in conjunction with the reported cytogenetic abnormalities, suggests that mesenchymal hamartoma may be a true neoplasm and not a developmental anomaly or reactive process.