Biomedical subjects

J I Diaz

Publications and source records attributed to J I Diaz.

18 recordsLinked to original sources

PubMed2005

In search of candidate genes critically expressed in the human endometrium during the window of implantation.

BACKGROUND: In this prospective randomized blinded clinical trial, we examined gene expression profiles of the human endometrium during the early and mid-luteal phases of the natural cycle. METHODS: An endometrial biopsy was performed on day 16 (LH +3) or on day 21 (LH +8), followed by RNA extraction and microarray analysis using an Affymetrix HG-U95A microchip. Data analysis was carried out using pairwise multiple group comparison with the significance analysis of microarrays (SAM) software. RESULTS: With a false discovery rate of 0, the analysis revealed that 107 genes were significantly and differently expressed (> or =2-fold) during the early versus the mid-luteal phase of the cycle. Forty-five of these genes have not been previously linked to endometrial receptivity. Validation of the microarray data was accomplished using semiquantitative RT-PCR. We demonstrated the presence of estrogen and progesterone response elements (ERE and PRE) by analysis of the 5'-flanking regions of a subset of differentially regulated genes. CONCLUSIONS: Using a strict bioinformatics approach of microarray data, we demonstrated significant changes in candidate genes during the transition of the early to the mid-luteal phase of the human endometrium that may have functional significance for the opening and maintenance of the window of implantation.

Adult↗

PubMed2000

Postradiation therapy adenosquamous cell carcinoma of the prostate.

The objective of this study was to present two cases of adenosquamous cell carcinoma of the prostate following radiation therapy. Two patients with history of prostate cancer treated with radiation therapy presented with rectal bleeding and a large ulcerated rectal mass. The rectal biopsy revealed on both cases squamous cell carcinoma. The initial diagnosis was invasive squamous cell carcinoma from anal origin. Both patients underwent pelvic exenteration with continent urinary diversion. After extensive histological sampling and immuno-histochemisty, they were correctly diagnosed of adenosquamous cell carcinoma of the prostate with invasion of the rectum. The patients died 6 and 16 months after surgery with widespread metastases. A review of the literature is presented. Adenosquamous cell carcinoma of the prostate is an unusual histological variant of prostate cancer. To our knowledge, only three cases of adenosquamous cell carcinoma of the prostate following radiation therapy have been reported. The unusual clinical and histopathological features of the two cases reported here led to an initial mistaken diagnosis. Adenosquamous cell carcinoma of the prostate should be considered in the differential diagnosis when a patient with prostate cancer develops a rectal mass or rectal bleeding following radiation therapy and the rectal biopsy reveals squamous cell carcinoma. Prostate Cancer and Prostatic Diseases (2000) 3, 53-56

Journal Article↗

PubMed1999

Predictability of PSA failure in prostate cancer by computerized cytometric assessment of tumoral cell proliferation.

OBJECTIVES: To evaluate the relationship of DNA ploidy and cell proliferation (CP) with Gleason score (GS) and clinical outcome in prostate cancer. METHODS: Sixteen patients with benign prostatic hyperplasia (BPH) and 65 patients with prostate cancer classified by GS (four groups: 2 to 4, 5 to 6, 7, and 8 to 10) were studied. All patients with carcinoma underwent prostatectomy and were separated into prostate-specific antigen (PSA) failure and nonfailure groups (failure if PSA 0.1 ng/mL or more three times after surgery). Tumoral CP (Ki-67 inmunostaining and SG2M phase) and DNA ploidy were evaluated by computerized cytometry. RESULTS: BPH were diploid with low CP (8% SG2M cells or less). Carcinomas were either diploid with high CP (greater than 8% SG2M cells) or aneuploid. CP was significantly higher (P <0.001) in tumors with GS 7 or greater than in tumors with GS less than 7 (mean percent Ki-67 cells 18.3% versus 7.8%, respectively). PSA failure increased with GS (7.1% in GS 2 to 4, 21% in GS 5 to 6, 28.6% in GS 7, and 50% in GS 8 to 10), as well as with aneuploidy (18.5% in diploid tumors versus 72.7% in aneuploid tumors). Those experiencing PSA failure had significantly higher (P <0.001) CP than those not failing (mean percent Ki-67 cells 24% and mean percent SG2M 30.4% versus 8.7% and 13.5%, respectively). Cox regression analysis showed GS, DNA ploidy, Ki-67, and SG2M to each be univariately prognostic for time to PSA failure; however, Ki-67 and SG2M were more highly significant (P <0.0001 for both) than GS (P = 0.007) or DNA ploidy (P = 0.002). After adjusting for either SG2M or Ki-67 measures of CP, neither ploidy nor GS contained additional prognostic value. CONCLUSIONS: Tumor CP and DNA ploidy can be reliably determined in prostate cancer by computerized cytometry. On the basis of our preliminary results, CP correlates well with GS and predicts PSA failure better than DNA ploidy or GS.

Aged↗

PubMed1999

Retinoblastoma protein expression leads to reduced Oct-1 DNA binding activity and enhances interleukin-8 expression.

Tumor cell lines with a defective retinoblastoma gene are unable to transcribe the HLA class II genes in response to IFN-gamma treatment, and reconstitution of functional Rb rescues IFN-gamma-induced class II gene expression. However, the molecular mechanism of Rb rescue of the class II genes is unknown. We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA, the prototype class II gene. Oct-1, a POU domain transcription factor, was identified as a repressor of HLA-DRA promoter activity in the Rb-defective cells. Rb expression led to phosphorylation of Oct-1, thus relieving its repressive effect. Oct-1 has also been shown to repress interleukin 8 promoter activity. Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines, interleukin 8 expression is higher in these cell lines.

Blotting, Western↗

PubMed1997

Prostate cancer.

Prostate cancer is the most common cancer in American men and the second leading cause of death in men aged 65 years or older. This article reviews the epidemiology and the principles of screening and management of prostate cancer.

Aged↗

PubMed1996

Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocyte-macrophage colony-stimulating factor.

The signal pathway for control of apoptosis in human neutrophils is currently unknown. In this study, we provide the first evidence that a Src family tyrosine kinase, Lyn, plays a key role in inhibition polymorphonuclear (PMN) cell death. Several nuclear proteins associated with apoptosis, i.e., p53, cdc2, and Rb, were absent from PMN. Bcl-2, known to inhibit apoptosis, was also not expressed. Programmed cell death that rapidly occurred in PMN could be arrested by granulocyte-macrophage CSF (GM-CSF), but this activation did not induce p53, cdc2, retinoblastoma, or Bcl-2 expression. Instead, GM-CSF produced a rapid activation of Lyn and Hck, but not Fgr, tyrosine phosphorylation within 1 min. Co-immunoprecipitation studies indicated that only Lyn, but not Hck, was physically coupled to GM-CSF receptor. By histologic assessment and evaluation of DNA fragmentation, only antisense Lyn, but not antisense Hck or antisense Fgr, could reverse the cell survival advantage provided by GM-CSF. Therefore, the physical coupling of Lyn to GM-CSF receptor and its early activation are required for inhibition or delay of apoptosis in PMN.

Apoptosis↗

PubMed1996

Ancillary techniques in the followup of transitional cell carcinoma: a comparison of cytology, histology and deoxyribonucleic acid image analysis cytometry in 91 patients.

PURPOSE: Voided urine and bladder washing cytology are used frequently in the evaluation of transitional cell carcinoma of the bladder. As part of an ongoing investigation we report on the role of deoxyribonucleic acid (DNA) image analysis cytometry as an adjunct to cytology in the followup of patients with transitional cell carcinoma. MATERIALS AND METHODS: Urine cytology and image analysis cytometry were performed independently on aliquots of voided urine, catheterized urine or bladder washings from 91 patients with previous or active transitional cell carcinoma of the bladder, and the results were compared to those of concurrent biopsy and clinical followup. RESULTS: Of 75 recurrent transitional cell carcinomas 42 were detected by cytology, while 63 and 64 were identified by image analysis cytometry and biopsy, respectively, for a sensitivity of 57, 84 and 85%, respectively. Combined cytology and image analysis cytometry detected 67 recurrences, for an overall sensitivity of 89%. Of 11 cases undetected by concurrent biopsy 9 had abnormal DNA histograms with transitional cell carcinoma at followup and 2 were DNA diploid but with grade 1 transitional cell carcinoma at followup. Of 12 cases undetected by image analysis cytometry 8 were grade 1 and 4 were grade 2 transitional cell carcinoma. CONCLUSIONS: Urine cytology and image analysis cytometry detect most recurrent tumors. Their combined use is indicated in the followup of patients with bladder transitional cell carcinoma.

Adult↗

PubMed1996

Macrophage expression of interleukin-1 in lymphoepithelioid cell ("Lennert's") lymphoma.

Macrophage activation was studied in three cases of a genuine form of T cell non-Hodgkin's lymphoma particularly rich in epithelioid histiocytes, the so-called "lymphoepithelioid cell lymphoma" or "Lennert's lymphoma". Host tumor infiltrating macrophages actively produced Interleukin-1 as demonstrated by immunohistochemistry. The activated histiocytes also contained intracytoplasmic tumor cells which were either intact or at various stages of apoptosis. We postulate that in Lennert's lymphoma, tumor cells are capable of activating host macrophages. Initial macrophage activation is followed by IL-1 production with recruitment of additional macrophages accounting for the characteristic histological appearance of this tumor. The activated macrophages are also engaged in a phagocytic antitumoral response. Future studies should investigate if this host response can be potentiated.

Humans↗

PubMed1996

Memory T cell subsets in B cell non-Hodgkin's lymphomas.

Memory T cells were quantitated by three color flow cytometry in cell suspensions from biopsy specimens of 34 B cell non-Hodgkin's lymphomas (NHL) and 10 benign lymphoid hyperplasias (BLH). CD3+CD45R0-CD45RA+ (naive), CD3+CD45R0+CDRA- (memory) and total CD3+ T cells were compared in BLH, low grade (LG), intermediate (IG) and high grade (HG) B cell NHL. Mean percentage +/- s.e. of CD45R0 + T cells for BLH, LG, IG and HG NHL were: 14.7 +/- 3.8, 11.2 +/- 3.5, 28.9 +/- 7.5 and 45 +/- 15, respectively. Mean percentage +/- s.e. of CD45RA+ T cells were: 10.2 +/- 2.6, 7.1 +/- 2.3, 5.4 +/- 1.4 and 3.5 +/- 1.2, respectively. Mean percentage +/- s.e. of total CD3+ T cells were: 42.5 +/- 11, 22.4 +/- 7.5, 39.3 +/- 10.1 and 62.7 +/- 22.2, respectively. Memory and total T cells progressively increased from LG toward IG and HG NHL while naive T cells simultaneously decreased. Although the differences in naive T cells were non-significant, the differences in memory T cells were significant between LG and IG and LG and HG NHL (both p < .0100). We previously reported an increase in activated-cytotoxic T cells in IG -HG B cell NHL. We now report that this subset of lymphocytes has also acquired memory function. Future studies should determine if in vitro expansion and adoptive transfer of this subset of T cells results in tumor cytolysis.

B-Lymphocytes↗

PubMed1996

Metastatic seminoma simulating malignant lymphoma in an HIV infected hemophiliac.

Although most common, malignant lymphoma and Kaposi's sarcoma are not the only malignancies encountered in lymph nodes from HIV-infected patients. An increased frequency of testicular germ cell tumors in HIV-infected individuals has been reported. We report here the first case, to our knowledge, of a metastatic seminoma in an HIV-infected hemophiliac. The atypical clinical presentation, cervical and axillary adenopathy, simulated malignant lymphoma. The diagnosis was first suspected when a fine needle aspiration biopsy from an enlarged cervical node revealed a mixture of benign appearing lymphocytes and loosely cohesive large tumor cells in a "tigroid" background. Immunocytochemistry and a subsequent excisional biopsy confirmed the cytologic diagnosis. Metastatic germ cell tumors should be considered in the differential diagnosis of HIV-related lymphadenopathy.

Adult↗

PubMed1995

Role of extracellular adenosine triphosphate in the cytotoxic T-lymphocyte-mediated lysis of antigen presenting cells.

The lysis of antigen presenting cells (APCs) by cytotoxic T lymphocytes (CTLs) may be one mechanism whereby an immune response is downregulated by Staphylococcus superantigens. Disappearance of monocytes/macrophages from staphylococcal enterotoxin A (SEA)-activated peripheral blood mononuclear cell (PBMC) cultures, but not from control PBMC cultures was seen by flow cytometry. Recently, adenosine triphosphate (ATP) has been described as an effector molecule in CTL-mediated lysis of some murine tumor target cells. We have also shown that ATP caused the lysis of human macrophages, and that treatment of cells with interferon gamma (IFN gamma) rendered macrophages significantly more sensitive to ATP than untreated cells. To show that this purine nucleotide may play a role in modulating the immune system, we generated human CTLs that were stimulated with SEA, and used them as effector cells against SEA-pulsed autologous macrophages. CTLs were found to specifically lyse SEA-pulsed macrophages, while control, unpulsed, macrophages were unaffected. The addition of hexokinase, an enzyme that hydrolyzes ATP, significantly abrogated the killing of SEA-pulsed cells during the assay. In examining the mechanism of cytotoxicity, electron microscopy showed that macrophages incubated with both ATP and CTLs underwent necrosis, rather than apoptosis. From these results, it is suggested that ATP is released from CTLs during antigen presentation, and that IFN gamma-activated macrophages, which are inherently more sensitive to this mediator, are readily lysed and therefore removed from circulation, thus downregulating an immune response.

Adenosine Triphosphate↗

PubMed1994

Interleukin-2 prevention of apoptosis in human neutrophils.

Evidence is presented that interleukin (IL)-2 maintains viability of human polymorphonuclear cells (PMN) in culture by preventing these cells from undergoing programmed cell death (PCD) and induces the synthesis of new RNA and protein. Our laboratory has recently discovered that human PMN constitutively express IL-2 beta receptor and more importantly, PMN are able to respond functionally to IL-2 by enhanced growth inhibitory activity against an opportunistic fungal pathogen, Candida albicans. We now report that IL-2 was able to interfere with the PCD process and reduce the number of apoptotic PMN to < 40% in 72-h culture. Freshly isolated PMN usually underwent a time-dependent aging process and > 80% of PMN cultured in medium alone for 72 h showed morphologic features of PCD as depicted by hematoxylin and eosin staining as well as by electron microscopy. During the PCD process, untreated PMN not only exhibited condensed nuclear structure and decrease in cell size, but also displayed DNA fragmentation. DNA fragmentation in PMN was prevented by IL-2. Prevention of PCD by IL-2 was associated with an increase in new RNA and protein synthesis in PMN, which may reflect cytokine induction, such as tumor necrosis factor, as we have recently shown. Thus, our data expands our current understanding of PMN in that they may be an active component of the immune system, with a longer life-span when activated than expected.

Apoptosis↗

PubMed1994

Anti-glomerular and anti-tubular basement membrane nephritis in a renal allograft recipient with Alport's syndrome.

A 28-year-old deaf, white man with a clinical diagnosis of Alport's syndrome since 4 years of age experienced renal failure, fever, and mental status changes suggestive of vasculitis following his first cadaveric renal transplant; these symptoms and changes resolved after removal of the allograft. Immunohistological stains demonstrated intense linear deposition of IgG and C3 in glomerular and tubular basement membranes in the absence of glomerular crescents. One year later, a second renal transplant led to similar symptoms. A biopsy was performed 14 days after engraftment, which demonstrated intense linear deposition of IgG in glomerular and tubular basement membranes, but cellular crescents were not present. A serologic profile was ordered to evaluate the patient further for vasculitis, and during the evaluation, circulating anti-glomerular basement membrane and anti-tubular basement membrane antibodies were identified by indirect immunofluorescence microscopy (titer, > 1:320). An open biopsy specimen obtained during repair of a renal laceration demonstrated a crescentic glomerulonephritis with immunohistologic findings identical to those of previous biopsies. Anti-glomerular basement membrane nephritis should be suspected in any patient with Alport's syndrome in whom progressive renal failure develops following renal transplantation. Detection of anti-glomerular basement membrane/anti-tubular basement membrane antibodies will assure the diagnosis, and early initiation of plasmapheresis may be helpful to prevent further renal damage.

Adult↗

PubMed1993

Host tumor infiltrating lymphocytes in B cell non-Hodgkin's lymphomas.

Tumor-infiltrating T lymphocytes (TIL-T) were quantitated by three color flow cytometry in cell suspensions from excisional biopsy specimens of 43 B cell non-Hodgkin's lymphomas (NHL) and 8 benign lymphoid hyperplasias (BLH) to identify potential differences in host T cell responses. We quantitated three TIL-T subsets: CD3+CD4+CD8- (helper-inducer), CD3+CD4-CD8+ (suppressor-cytotoxic) and CD3+CD25-HLADr+ (long term activated TIL-T) and compared them in three diagnostic groups: BLH, low grade B cell NHL (LG NHL) and intermediate-high grade B cell NHL (IG-HG NHL). The following results were obtained: Mean percentage +/- s.e. of activated TIL-T for BLH, LG-NHL and IG-HG NHL: 10.3 +/- 1.9, 23.2 +/- 4.6 and 38.8 +/- 9.5, respectively. Mean percentage +/- s.e. of suppressor-cytotoxic TIL-T for same groups: 13.9 +/- 1.5, 14.9 +/- 1.9 and 34.4 +/- 4.5, respectively. Mean percentage +/- s.e. of helper-inducer TIL-T cells for the same groups was 38.2 +/- 12.7, 32.1 +/- 7.2 and 22.5 +/- 4.6, respectively. Helper/suppressor ratio +/- s.e. for same groups was 3.0 +/- 1.1, 2.4 +/- 0.6 and 1.3 +/- 0.4, respectively. Activated and suppressor-cytotoxic TIL-T percentage progressively increased from BLH toward IG-HG NHL. The percentage of these two TIL-T subsets were significantly higher in IG-HG NHL than in BLH and LG-NHL (P < 0.0007, 0.0002, 0.0001 and 0.0260 for the comparisons TIL-T in BLH vs IG-HG NHL and LG-NHL vs IG-HG respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

PubMed1992

Ovarian follicular cysts: a potential source of false positive diagnoses in ovarian cytology.

The cytology samples of 22 benign ovarian cysts aspirated during laparoscopy (16) or laparotomy (6) were evaluated for clinicopathologic correlations. Clinically, most patients were evaluated for chronic pelvic pain. The cysts ranged in size from 1 to 5 cm (average 2.4 cm), and were described as having benign appearance. Cytologically, small granulosa cells arranged in clusters or isolated had granular cytoplasm with occasional microvacuoles. The nuclei were round to oval, uniform, and eccentrically placed. They had granular chromatin with chromocenters and one to two micronucleoli. Relative nuclear area averaged 50%. Mitoses were present in all but two cases, ranging from 0 to 38 mitoses per 10 high power fields (average 7.2 mitoses per 10 high power fields). Present in some cases were mesothelial cells and histiocytes. Three cases with follow-up histopathology specimens revealed two follicular cysts and a collapsed cyst without discernible lining. The immature appearance of the granulosa cells, the granular chromatin, and the presence of mitoses often suggested cytologically the possibility of a neoplastic process. Recognition of the cytopathology features, knowledge of the clinical history, and the laparoscopic findings may reassure the pathologist about the benign nature of the cysts.

Adolescent↗

PubMed1991

Activated T-cell subsets in benign lymphoid hyperplasias and B-cell non-Hodgkin's lymphomas.

Activated tumor-infiltrating T lymphocytes (TIL-T) were quantitated prospectively in excisional biopsy specimens of 49 B-cell non-Hodgkin's lymphomas (NHL) of various grades and compared with eight benign lymphoid hyperplasias (BLH) to identify any potential difference in host T-cell response. Immunotyping of tissue-cell suspensions was done by three-color flow cytometry, which was complemented by immunocytology by using cytocentrifuged preparations. Two activated T-cell subsets were studied: acutely activated TIL-T (CD3+ CD25+ HLADr-) and chronically activated TIL-T (CD3+ CD25- HLADr+). Results showed an association of the more aggressive intermediate/high-grade B-cell NHL with a higher percentage of late-phase activated TIL-T and a progressive increase with the grade of malignancy: 10.29%, 23.25%, 33.87%, and 47.78% (means) for BLH and for low-, intermediate- and high-grade B-cell NHL, respectively. Differences for this subset were significant (P less than 0.050) for the following comparisons: hyperplasia versus intermediate-grade NHL (P less than 0.0012), hyperplasia versus high-grade NHL (P less than 0.0002), and low versus high-grade NHL (P less than 0.0080). The percentage of acutely activated TIL-T cells did not show a statistically significant difference between the groups. The results suggest a host T-cell response to proliferating neoplastic cells in B-cell NHL. Paradoxically, the response does not appear to be protective for the host since the intensity is directly proportional to the grade of malignancy. However, the recognition of this response may have clinical applications since its amplification with biological response modifiers may result in effective adoptive immunotherapy of B-cell NHL. Further clarification of the specificity and biologic significance of host T-cell activation in B-cell NHL will require functional studies of isolated lymphocytic subpopulations from neoplastic tissue.

B-Lymphocytes↗

PubMedDate not supplied

Dog heartworm causing necrotizing granuloma of the lung.

Pulmonary dirofilariasis was diagnosed in a 70-year-old woman by tissue examination after she underwent a right thoracotomy. The preliminary clinical diagnosis was pulmonary coin lesion of probable neoplastic nature. Pulmonary dirofilariasis, caused by the dog heartworm, is occurring with increased frequency in the United States and must be considered in the differential diagnosis of pulmonary coin lesions. We describe the clinicopathological features of this case with special emphasis on the gross examination of the specimen.

Aged↗

PubMedDate not supplied

Differential diagnosis of endometrial hyperplasia and carcinoma by computerized image cytometry of cell proliferation, apoptosis and Bcl-2 expression.

BACKGROUND: The differential diagnosis between atypical endometrial hyperplasia and endometrial carcinoma is often difficult and based on controversial criteria. Cell kinetic parameters may be helpful. DESIGN: Cell proliferation, apoptosis and Bcl-2 expression were evaluated in benign endometrium, non atypical and atypical endometrial hyperplasia and endometrial carcinoma. The results were compared by one way analysis of variance and Bonferroni T tests. RESULTS: Cell proliferation was significantly higher (p < 0.01) in endometrial adenocarcinoma (25.6 percent) than in atypical hyperplasia (17.1 percent) and non-atypical hyperplasia (7.5 percent) of the endometrium. Apoptosis was observed in 12.3 percent of endometrial adenocarcinomas and less frequently in atypical hyperplasia (7.4 percent) and non-atypical hyperplasia of the endometrium (5.8 percent). Bcl-2 expression was significantly lower (p < 0.002) in endometrial adenocarcinoma (1.7 percent) than in atypical hyperplasia (4.2 percent) and non-atypical hyperplasia (5.3 percent) of the endometrium. In benign endometrium, cell proliferation and Bcl-2 expression were significantly higher during the proliferative phase while the rate of apoptosis was significantly higher during the secretory phase. CONCLUSIONS: Our data suggests that cell proliferation, apoptosis and Bcl-2 expression could be helpful when distinguishing endometrial carcinoma from non-atypical or atypical endometrial hyperplasia.

Adult↗