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ABSTRACT: We studied the magnitude, significance, and origin of an analytic bias that emerged between our point-of-care (POC) and our central laboratory (CL) methods for the measurement of hemoglobin A1c (HbA1c) and evaluated the analytic accuracy of 7 commonly used HbA1c methods relative to the National Glycohemoglobin Standardization Program (NGSP) reference method. The POC and CL methods were compared by split-sample analysis of clinical specimens and time series analyses of the HbA1c results reported for a 33-month period. The relative accuracies of 7 HbA1c methods were evaluated using College of American Pathologists proficiency survey results. Long-term drifts in the CL- and POC-analyzed test results caused the median intermethod bias [(POC result)-(CL result)] to increase from -0.4% to -0.9% HbA1c. Systematic biases, drifts in analytic performance over time, and intermethod variability were frequently observed among the 7 NGSP-certified HbA1c methods. Intermethod variability is a potential source of inaccuracy whenever HbA1c results are interpreted relative to universal, fixed, clinical decision thresholds.
American Journal of Clinical Pathology 05/2008; 129(4):540-7. · 2.60 Impact Factor
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ABSTRACT: Myeloid sarcoma is a tumor of myeloblasts or immature myeloid cells occurring in an extramedullary site. Myeloid sarcoma of female genital tract is very rare with no cases of vulvar location reported in English-language literature.
A 73-year-old female presented with an indurated mass encompassing her left labia majora and vulva. The mass was diagnosed as vulvar myeloid sarcoma. The patient's peripheral blood smear revealed Auer rods and other findings consistent with a diagnosis of acute myeloid leukemia (M-2 type, FAB classification).
To the best of our knowledge this case is the first report in the English-language literature of the myeloid sarcoma of the vulva. Correct diagnosis of myeloid sarcoma in an otherwise asymptomatic patient is crucial for early administration of antileukemic chemotherapy.
Gynecologic Oncology 08/2007; 106(1):259-61. · 3.89 Impact Factor
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Diagnostic Cytopathology 06/2006; 34(5):349-50. · 1.16 Impact Factor
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ABSTRACT: Mesonephric adenocarcinoma of the vagina is exceedingly rare, with only one well-documented case in the literature. Little is known regarding clinical presentation, pathological characteristics, therapy, or prognosis of the vaginal mesonephric adenocarcinoma.
A 55-year-old woman presented with a polypoid mass at the right vaginal apex, extending to the right paravaginal tissue. The tumor was an adenocarcinoma with ductal and tubular pattern arising in a background of mesonephric remnants. Tumor cells showed immunoreactivity for pankeratin, epithelial membrane antigen (EMA), and calretinin. The right fallopian tube and one paravaginal lymph node were positive for metastases. The patient is disease-free 3 years after surgery, radiation therapy, and chemotherapy.
We report the second case of mesonephric adenocarcinoma of the vagina with metastasis to the right fallopian tube and to one paravaginal lymph node.
Gynecologic Oncology 01/2006; 99(3):757-60. · 3.89 Impact Factor
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Archives of pathology & laboratory medicine 05/2005; 129(4):537-8. · 2.58 Impact Factor
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ABSTRACT: Verruciform xanthoma (VX) is a rare lesion with a predilection for oral mucosa. Only 16 cases of VX of the penis have been reported. Histologically, VX lesions in different locations are identical; however, the etiology is controversial. Previous studies have reported the presence of human papillomavirus (HPV) in VX of the skin. The purpose of this study was to determine whether HPV is a causative agent in this rare case of VX of the penis. Microscopically, the lesion demonstrated prominent verrucoid squamous hyperplasia with hyperkeratosis, parakeratosis, and acanthosis. Histiocytes, a hallmark of VX, were identified in the elongated dermal papillae. Nested polymerase chain reaction was performed on the DNA with the commonly used primer sets MY9/MY11 and GP5+/GP6+, which identify more than 40 HPV types. The results failed to identify HPV DNA in the sample, although HPV could be readily detected in genomic DNA extracted from paraffin-embedded condyloma acuminatum, a known HPV-associated lesion. Additionally, we tested a VX lesion of the palate for HPV DNA and obtained negative results. Our results indicate that VX can arise without HPV infection and suggest other possible origins may be involved.
Archives of pathology & laboratory medicine 04/2005; 129(3):e62-4. · 2.58 Impact Factor
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ABSTRACT: Aminopeptidase P (APP) isoforms specifically remove the N-terminal amino acid from peptides that have a proline residue in the second position. The mRNA levels of three different isoforms, each coded by a different gene, were determined in 16 human tissues and in peripheral blood mononuclear cell (PBMC) fractions by RT-PCR. The cytosolic isoform, APP1, and the cell surface membrane-bound isoform, APP2, are expressed in all of the human tissues and PBMC fractions examined. The very high expression of APP2 mRNA in kidney compared to other tissues was confirmed by enzyme activity measurements. Among the PBMC fractions, APP2 expression is highest in resting CD8(+) T cells, but decreases in these cells following their activation with phytohemagglutinin; in contrast, expression of APP2 increases in CD4(+) T cells upon activation. The third isoform, APP3, is a hypothetical protein identified by nucleotide sequencing. A detailed analysis of its amino acid sequence confirmed that the protein is an aminopeptidase P-like enzyme with greater similarity to Escherichia coli APP than to either APP1 or APP2. Two splice variants of APP3 exist, one of which is predicted to have a mitochondrial localization (APP3m) while the other is cytosolic (APP3c). Both forms are variably expressed in all of the human tissues and PBMC fractions examined.
Archives of Biochemistry and Biophysics 04/2005; 435(2):303-10. · 2.93 Impact Factor
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ABSTRACT: Membrane-bound aminopeptidase P (mAPP) is a highly specific exopeptidase that removes the N-terminal amino acid only from a peptide (three amino acids or longer) that has a prolyl residue in the second position. mAPP can inactivate bradykinin, a potent vasodilating and cardioprotective peptide hormone, by hydrolyzing the Arg(1)-Pro(2) bond. Studies on the rat have shown that the metabolism of bradykinin is an important physiological role of this enzyme. We report here the complete coding sequences for rat and mouse mAPP determined from mRNA isolated from lung tissue. Key structural features that determine post-translational processing and substrate recognition and catalysis were identified based on sequence homologies and the crystal structure of Escherichia coli aminopeptidase P complexed with Pro-Leu. The tissue-specific expression of mAPP was studied using the polymerase chain reaction. The mAPP gene is widely, but variably, expressed in adult tissues of the rat and mouse and in mouse embryos.
Archives of Biochemistry and Biophysics 10/2003; 417(2):131-40. · 2.93 Impact Factor
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ABSTRACT: This study investigated the receptor mechanism(s) by which the hormone melatonin directly affects ovarian function. Expression of MT1 and MT2 melatonin receptor mRNA was detected in the rat ovaries both by reverse transcriptase-polymerase chain reaction and in situ hybridization with digoxigenin-labeled oligoprobes. Specific 2-[125I]iodomelatonin binding was significantly higher in ovarian tissue from animals sacrificed during proestrus than in metestrus, suggesting regulation of melatonin receptors by estrogens. Additionally, basal and melatonin-mediated stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding to ovarian sections was higher in proestrus compared with metestrus. During proestrus, both luzindole (0.1 microM) and 4-phenyl-2-propionamidotetraline (4P-PDOT) (0.1 microM), acting as inverse agonists, inhibited basal [35S]GTPgammaS binding to ovarian sections, suggesting the presence of MT1 constitutively active melatonin receptors. In primary cultures of ovarian granulosa cells, melatonin inhibited forskolin-stimulated cAMP accumulation through activation of Gi-coupled melatonin receptors. This inhibition was blocked by both, luzindole, and 4P-PDOT, acting as competitive receptor antagonists. Exposure of granulosa cells in culture to 17beta-estradiol seems to alter the state of melatonin receptor coupling. Indeed, the efficacy of 4P-PDOT on forskolin-stimulated cAMP formation was reversed from an MT2 partial agonist in vehicle-treated cells to that of an MT1 inverse agonist in 17beta-estradiol (0.1 microM)-treated granulosa cells. We conclude that MT1 and MT2 melatonin receptors expressed in antral follicles and corpus luteum may affect steroidogenesis through cAMP-mediated signaling. These results underscore the implications of the levels of ovarian estrogen when melatonin receptor ligands are used as therapeutic agents.
Journal of Pharmacology and Experimental Therapeutics 09/2003; 306(2):694-702. · 3.83 Impact Factor
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ABSTRACT: This study assessed the state of melatonin MT(1) receptor coupling in sections of male rat caudal arteries by [35S]GTPgammaS binding autoradiography. The melatonin MT(1) receptor inverse agonist 4-phenyl-2-propionamidotetraline (4P-PDOT) (0.1-1 microM) significantly decreased [35S]GTPgammaS binding compared to basal, strongly suggesting the presence of constitutively active receptors. Formation of constitutively active receptors during subjective day, when the levels of melatonin are low, may be a physiological mechanism by which the organism maintains vascular tone.
European Journal of Pharmacology 04/2002; 439(1-3):171-2. · 2.52 Impact Factor
