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Biomedical subjects

C G Pantazis

Publications and source records attributed to C G Pantazis.

At least 19 recordsLinked to original sources

Langerhans cell granulomatosis manifested as pigmented villonodular synovitis.

We report an unusual case of Langerhans cell granulomatosis (LCG) manifested as a villous synovial proliferation in a 38-year-old female jogger. One year after the onset of joint symptoms, she had a classical LCG presentation with skin and visceral lymph node involvement. Review of the literature revealed only one case of synovial shoulder joint tenosynovitis associated with LCG in a middle-aged woman. Ours is the first reported case presenting clinically in the synovium of the hip joint as pigmented villonodular synovitis. Histiocytic/dendritic proliferations involving the synovial tissues are not uncommon. These lesions as well as the rare multicentric reticulohistiocytosis (MRH), a systemic monocytoid/histiocytic disorder with multinucleated giant cells, polyarthritis, and papulonodular skin lesions, should be considered in the differential diagnosis. Clinical and pathologic features will distinguish LCG from MRH.

Adult↗

Constitutive activation of stimulatory guanine nucleotide binding protein (G(S)alphaQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells.

An abnormal stimulation of cAMP signaling cascade has been implicated in various human carcinomas. Since the agents activating G(S)alpha-mediated signaling pathways have been shown to increase in vitro proliferation of prostate cancer cells, present studies examined the G(S)alpha-mediated signaling in tumorigenicity and invasiveness of PC-3M prostate cancer cells. PC-3M cells were stably transfected with plasmids containing either wild type (G(S)alpha-WT) or constitutively active (gsp mutant of G(S)alpha or G(S)alpha-QL) cDNAs. The stable transfectants were then tested for: (1) colony formation in soft agar; (2) cell migration and penetration of basement matrix in an in vitro invasion assay; and (3) the ability to form tumors and metastases in nude mice. PC-3M cells expressing G(S)alpha-QL protein displayed 15-fold increase in their ability to migrate and penetrate the basement membrane as compared to parental PC-3M cells or those expressing G(S)alpha-WT. G(S)alpha-QL transfectants also displayed a dramatically greater rate of growth in soft agar, and greater tumorigenicity and metastasis forming ability when orthotopically implanted in nude mice. All mice receiving PC-3M cells produced primary tumors within 5 weeks after implantation. However, the cells expressing G(S)alpha-QL displayed a significantly faster tumor growth as assessed by prostate weight (greater than 20-fold as compared to PC-3M cells), and produced metastases in kidneys, lymph nodes, blood vessels, bowel mesentery and intestine. Interestingly, expression of G(S)alpha-WT reduced the ability of PC-3M cells to form tumors in nude mice. These results suggest that persistent activation of G(S)alpha-mediated signaling cascade can dramatically accelerate tumorigenesis and metastasizing ability of prostate cancer cells.

Animals↗

Small cell carcinoma of urinary bladder is differentiated from urothelial carcinoma by chromogranin expression, absence of CD44 variant 6 expression, a unique pattern of cytokeratin expression, and more intense gamma-enolase expression.

AIMS: Small cell (neuroendocrine) carcinoma of the urinary bladder is clinically more aggressive than urothelial (transitional cell) carcinoma. We have investigated the immunohistochemical markers most useful in diagnosing small cell carcinoma in bladder. METHODS AND RESULTS: We evaluated the expression of chromogranin A, CD44 variant 6 (CD44v6), cytokeratin (CAM 5.2), gamma-enolase, synaptophysin, and CD45 in 46 small cell carcinomas of the bladder. Small cell and urothelial carcinoma were mixed in 21 (46%) cases. The two immunohistochemical markers with best ability to discriminate between small cell and urothelial carcinoma were chromogranin A and CD44v6. Chromogranin A had 97% specificity for small cell carcinoma, staining 65% of cases with 2+/3+ mean intensity; only one case (5%) of urothelial carcinoma was weakly (1+/3+) positive. CD44v6 was 80% specific for urothelial carcinoma, with immunoreactivity in 60% of cases, compared with 7% of small cell carcinoma cases. In cases positive for CD44v6, the mean percentage of reactive urothelial carcinoma cells was 75% (range 10-100%), greater than the 12% of cells in three cases of small cell carcinoma (P = 0.31); further, the pattern of immunoreactivity was membranous vs. focal cytoplasmic, respectively. All small cell carcinomas stained with one of the three neuroendocrine markers tested; 76% of cases were reactive for synaptophysin and 93% for gamma-enolase, with specificities of 86% and 73% in comparison to urothelial carcinoma. gamma-enolase staining of small cell carcinoma was more intense (P = 0.01) than for urothelial carcinoma. Cytokeratin CAM 5.2 stained a mean 47% of cells in small cell carcinoma, always in a punctate perinuclear pattern, and 75% in urothelial carcinoma, in a membranous pattern. CONCLUSIONS: CD44v6, chromogranin A, and possibly gamma-enolase and cytokeratin (CAM 5.2) help differentiate small cell carcinoma from urothelial carcinoma.

Adult↗

Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors.

Both endogenous and exogenous estrogen exposure is associated with an increased breast cancer risk. In some studies, elevated serum testosterone levels have also been linked to an increased breast cancer risk. Estrogen alone or combined with progesterone induces high mammary tumor incidences in various strains of both male and female rats. Mammary gland ductal adenocarcinomas were induced after 17beta-estradiol (E2) and testosterone propionate (TP) treatment in male Noble rats. Tumor incidence was 100% after 8-9 months of treatment. Such neoplasms were not detected after either estrogen or androgen exposure alone within this time period. TP alone caused disruption of mammary gland ducts and proliferation of stromal tissue, while E2 treatment alone induced both ductal epithelial growth and nodular atypical hyperplasia. To study the interaction of these hormones in mammary tumorigenesis, sex hormone receptors were characterized in mammary glands of Noble rats. Estrogen receptor-alpha (ER) was detected in age-matched, untreated mammary gland epithelium; in most early atypical hyperplastic lesions appearing after E2 and E2 + TP treatment and in E2 + TP-induced mammary tumors. Two major ER putative isoforms, 116 and 120 kDa, were detected in E2- and E2 + TP-treated mammary glands, and in the induced tumors. A 54 kDa ER protein was found in untreated and TP-treated mammary glands, and in the induced tumors. Both progesterone receptor-B (PR-B) and PR-A2, as well as androgen receptor-B (AR-B) and AR-A isoforms were markedly elevated in all E2 + TP-induced mammary tumors. However, the levels of both PR and AR were very low in mammary glands of E2- and E2 + TP-treated male rats. Low and moderate levels of AR and PR, respectively, were detected in most atypical hyperplastic lesions induced by E2- and E2 + TP-treated mammary glands. These results suggest that androgens may interact with either AR or PR, and perhaps both receptors, in E2 + TP-induced mammary glands and the induced tumors to effect the reduction in latency period, enhance tumor size, and increase incidence to 100%.

Adenocarcinoma↗

Induction of cathepsin D protein during estrogen carcinogenesis: possible role in estrogen-mediated kidney tubular cell damage.

We have proposed that an early step in estrogen carcinogenesis in the hamster kidney is tubular damage followed by reparative cell proliferation. This tubular injury is progressive and increases in severity with continued estrogen treatment; one pertinent feature is a marked rise in the number of both secondary and tertiary lysosomes. Data presented herein indicate that cathepsin D, an estrogen-responsive lysosomal proteolytic enzyme, is increased in the kidney following estrogen treatment in the hamster. Three isoforms of cathepsin D were detected in estrogen-treated kidneys, 52, 31, and 27 kDa, the major being 52 kDa. At 1 and 3 months of estrogen treatment, 52-kDa cathepsin D content increased 1.4- to 1.6-fold. These changes coincided with a rise in renal estrogen receptor levels during the same estrogen treatment periods. More pronounced rises in cathepsin D levels, 2.7- and 3.5-fold, were seen after 4 and 5 months of estrogen treatment, respectively. A concomitant, 3.0- to 4.0-fold rise in estrogen receptor content was also observed. At 5 months of estradiol or DES treatment, both 27- and 31-kDa isoforms were present in hamster kidneys, in addition to the 52-kDa form. Neither progesterone nor DHT treatment affected the untreated levels of cathepsin D. Interestingly, either concomitant tamoxifen or DHT and estrogen treatment prevented the rise in cathepsin D and estrogen receptor content observed after estrogen treatment alone. Primary estrogen-induced renal tumors and their metastases exhibited markedly elevated levels of all three isoforms of cathepsin D. Immunohistochemical analysis of cathepsin D in kidney sections confirmed the Western blot findings. These data suggest a novel role for estrogen-induced cathepsin D in the hamster kidney during tumorigenesis; that is, mediating renal tubular damage as a prelude to reparative cell proliferation, thus initiating a multi-step estrogen-driven process which leads to renal tumor formation.

Animals↗

Extensive extramedullary disease in myeloma. An uncommon variant with features of poor prognosis and dedifferentiation.

BACKGROUND: The development of extramedullary plasmacytomas and elevated serum lactic dehydrogenase (LDH) in myeloma indicates poor prognosis. A 75-year-old man was diagnosed with immunoglobulin (Ig) A, lambda myeloma when he developed pathologic rib fractures, hypercalcemia, and anemia. After 6 months of treatment with melphalan and prednisone, he was in complete remission as evidenced by the disappearance of the monoclonal protein in the serum and free light chain in the urine. Eight months after diagnosis, his disease took an unusual course with the simultaneous development of plasmacytomas in the skin, breast, stomach, and pancreatic head, complicated by severe upper gastrointestinal bleeding and obstructive jaundice. METHODS: Immunohistochemical staining of the marrow and breast mass was done using monoclonal antibodies against B-cell and T-cell antigens as well as kappa and lambda light chains. In situ hybridization was performed to detect ras oncogene overexpression in the breast mass. RESULTS: Immunohistochemical staining of the original marrow and breast mass was positive for IgA and lambda, confirming the identical clonal origin of the plasma cells. The disorder expressed elevated serum LDH, both at diagnosis and relapses. Features of dedifferentiation were expressed by the disappearance of myeloma protein in the serum at relapse, absence of marrow plasma cell infiltration, and development of multiple extramedullary plasmacytomas. There was no overexpression of H-ras or N-ras oncogenes by in situ hybridization of the plasmacytoma from the breast. The patient died shortly after the development of the extramedullary plasmacytomas. CONCLUSIONS: The simultaneous appearance of plasmacytomas in multiple extramedullary sites heralds a change of clinical behavior in myeloma. When accompanied by the disappearance of serum myeloma protein, and marrow plasma cell infiltration, and serum LDH elevation, the disorder may follow a fulminant course.

Aged↗

Possible selective elimination of red blood cells under the influence of colloidal silica.

The physical interaction between the red blood cells and colloidal silica leads to hemolysis. We propose that the nature of the red-cell elimination as the result of this interaction is not random. As the negatively charged silica particles at the physiological conditions electrostatically react with the positive sites of the outer side of the cell membrane, it seems reasonable to suppose that the cells with a low density of negative charges on the membrane surface area are more probable to be lysed in the first place.

Cell Adhesion↗

Cervical thymic cysts: CT appearance of two cases including a persistent thymopharyngeal duct cyst.

The differential diagnosis of cervical cysts in children includes common entities such as branchial cleft cysts, thyroglossal duct cysts, and cystic hygromas. Congenital thymic cysts are uncommon and often misdiagnosed as either branchial cleft cysts or cystic hygromas. However, they may have an appearance on CT that can be characteristic. The course of the descent of embryologic thymic tissue in the neck to the mediastinum indicates the potential site of deposition of an ectopic cervical thymic cyst. In a child, a cystic lesion that has an intimate relationship to the carotid sheath is likely to be a thymic cyst. Of the approximately 100 cases of vestigial cervical thymus or thymic cysts that have been reported in children, only 5 cases of a persistent thymopharyngeal duct cyst have been described [1-5]. In two of these five, the persistent thymopharyngeal duct cyst was demonstrated by CT [1,2]. We report one additional case of a cervical thymic cyst and one case of a persistent thymopharyngeal duct cyst both depicted by CT.

Child, Preschool↗

Rapidly progressive CD8-positive cutaneous T-cell lymphoma with tongue involvement.

Cutaneous T-cell lymphoma rarely involves the oral cavity. We describe the histological and immunological findings of a rapidly progressive CD8+ cutaneous T-cell lymphoma involving the tongue. Involvement of the oral cavity usually indicates a poor prognosis. Cases of cutaneous T-cell lymphoma with oral involvement as reported in the English-language literature are reviewed and discussed.

Aged↗

Adsorption of aerosil on erythrocyte surface by flow cytometry measurements.

Light scattering properties of the erythrocytes in less than 0.01% aerosil suspension were measured. It was shown that light scattering properties of intact cells and cells associated with silica (aerosil) are different. It was also established that the aerosil particles are characterized by more intensive autofluorescence in the channel of green fluorescence than the erythrocytes. We propose that this observation allows a facile means of studying the interaction of purified silica and cell membranes. Hemolysis, as a result of interaction between the aerosil particles and the erythrocytes, was confirmed by photometric measurement of hemoglobin in the supernatant.

Adsorption↗

African-American factor VII-deficient variants in Georgia (FVII variants).

We studied African-American Factor (FVII)-deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme-linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII-deficient patients and 3 carriers demonstrated the following results: PT: 18.2 +/- 6.5 sec; FVIIAG: 73.0 +/- 14.9%; HRFVIIC: 30.6 +/- 20.3%; HPFVIIC: 30.5 +/- 21.4%; RBFVIIC: 25.3 +/- 21.4%; BBFVIIC: 30.6 +/- 17.5%; AMFVIIC: 44.1 +/- 18.3%. We conclude that a group of clinically mild African-American FVII-deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; and excellent correlation was noted for both human thromboplastins.

Antibodies↗

Pilomatrical carcinosarcoma of the cheek with subsequent pulmonary metastases. A case report.

We report a case of malignant pilomatrixoma with a pronounced biphenotypic morphology. The lesion, which was excised from the cheek of a 36-year-old man, was composed of a large pilomatrixoma lying within a spindled, sarcomatoid stroma. Fourteen months later, the tumor metastasized to the right upper lobe of the lung. We describe the tumor's pathology, histology, and immunochemistry and discuss the differential diagnosis. We also speculate on its histogenesis.

Adult↗

Inhibition of estrogen stimulated mitogenesis by 3-phenylacetylamino-2,6-piperidinedione and its para-hydroxy analog.

3-Phenylactetylamino-2,6-piperidinedione (A10) inhibited estradiol stimulated cell growth in the MCF-7 (E3) human breast tumor cell line in vivo and in vitro. While high concentrations of A10 were needed to inhibit cell proliferation (IC50 = 3 x 10(-3) M in vitro), the compound demonstrated little toxicity. The effect appeared specific since a hydrolysis product of A10, phenylacetylglutamine, demonstrated no growth inhibitory activity at similar concentrations in MCF-7 (E3) cells in vitro. A computer designed analog, p-hydroxy A10, was more potent than A10 in inhibiting activity in MCF-7 (E3) cells in vitro. The IC50 for p-hydroxy A10 was 7 x 10(-6) M which was comparable to that of the antiestrogen, tamoxifen (IC50 1 x 10(-7) M). All three compounds caused a decline in estrogen receptor levels in a dose-dependent fashion. A10 also inhibited estradiol induction of progesterone receptors. Examination of protein kinase activity following an acute exposure to a 10(-11) M growth stimulatory dose of estradiol revealed a 168% increase in protein kinase activity over that of untreated control cells. A10 in a dose-responsive fashion inhibited the estradiol stimulated increase in protein kinase activity. The protein kinase activity was also inhibited by p-hydroxy A10. These activities of A10 and p-hydroxy A10 coupled with the low toxicity and novelty of the basic A10 structure provide an exciting possibility of developing a new class of clinically useful antineoplastic drugs with minimal side effects.

Animals↗

Immunocytochemical study of insulin-like growth factor I and insulin-like growth factor I receptor in human endometrium during the normal menstrual cycle.

Our aims were to detect, using immunocytochemistry, IGFI and IGFI R in the human endometrium and to assess semiquantitatively their levels in the phases of the normal menstrual cycle. Twelve normal proliferative and 10 normal secretory endometrial samples were studied. Each specimen was subjected to an immunocytochemical peroxidase antiperoxidase protocol. The antibodies used to detect IGFI and IGFI R were, respectively, 3D1/2/1 and alpha 1R3. Analysis of variance (ANOVA) was performed to evaluate mean IGFI and IGFI R levels in the glandular epithelium and stroma of each sample while correcting for intra- and interobserver variation. These experiments show the presence of IGFI and IGFI R in human endometrium. There are significant variations in the IGFI and IGFI R levels from patient to patient within each cycle phase, and between glands and stroma within each sample. These findings highlight the importance of the use of in situ studies to clarify endometrial IGFI and IGFI R physiology.

Endometrium↗

An animal model of lymphatic metastasis using the ascites-form of the murine testicular teratocarcinoma (402AX).

We examined the ascites-form of the murine testicular teratocarcinoma (402AX) as an animal model of spontaneous metastasis. We inoculated 2 x 10(5) cells into a total of seven hundred and twenty-seven 129/J strain mice. They showed clinically manifested ascites approximately two weeks later and died three to nine weeks later. Metastases were seen in lungs and hilar lymph nodes two to three weeks later. We performed staging and developed a definition of metastasis. Pulmonary metastases were quantified by mapping and counting the number of metastatic nodules in the lungs. Lymph node metastases were quantified by measuring the maximum diameter of metastatic lymph nodes (tumors). Additional sectioning was shown to be beneficial to demonstrate lymph node metastasis. The macroscopical metastatic rate was much less than the microscopical metastatic rate. The metastatic rate of the natural-death mice was much higher than that of the sacrificed mice. Lymph node metastatic rate was much higher than pulmonary metastatic rate. The metastatic rate had a direct relationship with the volume of ascites. This animal model can be used to study spontaneous metastasis.

Animals↗

Failure of microchromatographic measurement of fetal hemoglobin in beta zero thalassemia-hereditary persistence of fetal hemoglobin.

We report microchromatographic measurement of fetal hemoglobin (HbF) proportions in a 36-year-old African-American multigravida woman. At 34 weeks she delivered a 630-g male infant who subsequently did well. Hemoglobin electrophoresis of the hemolysate revealed nearly 100% HbF without HbA, an extremely unusual naturally occurring sample. Family studies revealed a combination of hereditary persistence of fetal hemoglobin (HPFH) and beta zero-thalassemia minor. Southern blot technique confirmed heterozygous alpha 2 thalassemia and HPFH but failed to identify the beta thalassemic lesion. The absence of HbA and the very high amounts of HbF led us to measure HbF by several methods to confirm the accuracy of microchromatography of HbF at values approaching 100%. HPLC revealed a 14% F1 suggestive of microchromatographic underestimation due to glycated HbF. We conclude that cation-exchange microchromatography and the Betke method of alkali denaturation underestimate HbF values as they approach 100% and do not recommend these procedures in this rare situation.

Adult↗

Cytology and DNA flow cytometry of peritoneal washings in gynecologic patients.

Peritoneal washing cytology, widely used in the management of gynecologic malignancy, entails several difficulties in interpretation. Quantitative DNA analysis by flow cytometry (FCM) holds promise as a more objective method fo diagnosis of malignancy. We performed traditional cytologic examination and single-parameter FCM DNA analysis on peritoneal washings from 136 gynecologic laparotomies, compared these results with the final pathologic findings, and analyzed sources of error. A total of 50 laparotomies were performed for benign disease. Another 86 were performed for cervical, endometrial, and ovarian carcinomas and various other cancers. In the benign group, cytology had one false suspicious but no false positive results, and FCM showed only diploid cells. In the cancer cases, cytology had five suspicious and 13 positive results and one false negative from laboratory error. On review, 16 washings contained confirmed cancer cells. FCM, performed in 13 of these cases, was diploid in 10 and aneuploid in only 3. In six of the diploid cases, visual cell counts showed that tumor cells were present in concentrations of 2.5% or less of total cells. In the remaining four diploid cases, a second DNA determination was obtained by FCM of nuclei retrieved from paraffin blocks of the tumors. These nuclei were diploid by FCM in three of the tumors and aneuploid in only one. Single-parameter DNA FCM was too insensitive to be helpful in our material.

DNA↗

Recurrent renal cell carcinoma arising in Wilms' tumor.

A 19-month-old black girl had a radical nephrectomy for a Wilms' tumor that contained areas of epithelium indistinguishable from renal cell carcinoma. She was treated with chemotherapy but subsequently had pulmonary metastases develop and massive abdominal recurrence. The recurrent tumor was histologically renal cell carcinoma with no identifiable Wilms' tumor elements. The child died with recurrent and metastatic tumor 13 months after nephrectomy. Pathologic, immunoperoxidase, and flow cytometric studies of this unusual case are presented.

Carcinoma, Renal Cell↗