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Biomedical subjects

B Burke

Publications and source records attributed to B Burke.

At least 91 records · Page 5Linked to original sources
PubMed1990

Internuclear exchange of an inner nuclear membrane protein (p55) in heterokaryons: in vivo evidence for the interaction of p55 with the nuclear lamina.

The movement between nuclei of an integral protein of the inner nuclear membrane has been studied in rat/mouse and rat/hamster heterokaryons. This protein, p55, was found to equilibrate between nuclei over a period of approximately 6 h in the absence of new protein synthesis. When rat/mouse heterokaryons were constructed using an undifferentiated murine embryonal carcinoma (P19), which lacks lamins A and C, no accumulation of p55 in the mouse cell nucleus was observed. However, P19 nuclei could be rendered competent to accumulate p55 by transfecting the parent cells with human lamin A before cell fusion, supporting the notion that p55 may interact with the nuclear lamina. Since p55 does not appear to be able to dissociate from the nuclear membrane, it is concluded that this exchange between nuclei does not occur in the aqueous phase and instead is probably membrane mediated. It is proposed that this protein may be free to move between the inner and outer nuclear membranes via the continuities at the nuclear pore complexes and that transfer between nuclei occurs via lateral diffusion through the peripheral ER, which appears to form a single continuous membrane system in these heterokaryons. One implication of these observations is that accumulation of at least some integral proteins in the inner nuclear membrane may be mediated by interactions with other nuclear components and may not require a single defined targeting sequence.

Animals↗
PubMed1990

Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies.

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.

Antibodies, Monoclonal↗
PubMed1990

Anti-estradiol immunoperoxidase labeling of nuclei, not cytoplasm, in paraffin sections, determines estrogen receptor status of breast cancer.

We evaluated a commercially available polyclonal antibody to 17 beta-estradiol as the basis for an estrogen receptor (ER) assay of breast carcinoma in formalin-fixed paraffin tissues and then compared it with both the ER-ICA antibody in serial paraffin sections and the biochemical assay of corresponding fresh tissue. Using the estradiol antibody, 49 of 50 cases showed some cytoplasmic staining; 38 cases had nuclear staining. Sensitivity and specificity for different proportions of positive nuclear and cytoplasmic staining were calculated using receiver-operator characteristic curves. The optimum correlation with the biochemical assay was obtained with nuclear staining alone. Greater than 30% nuclear positivity as a cut-off point yielded a sensitivity of 76% and a specificity of 82%. The corresponding ER-ICA values in 38 cases yielded a sensitivity of 93% and a specificity of 56%. The methodology for the ER-ICA assay was more technically demanding in paraffin sections than that of the estradiol antibody and considerably more expensive. This study is the first to show that with nuclear staining only, and not cytoplasmic staining, as the parameter of positivity, the immunocytochemical assay of ER with anti-17 beta-estradiol antibody in routinely processed, formalin-fixed, archival material is an accurate and specific method for the determination of the ER status of breast carcinoma.

Antibodies, Monoclonal↗
PubMed1990

Dense intramembranous deposit disease: a clinical comparison of histological subtypes.

The accumulation of osmiophilic dense deposits in glomerular mesangial and basement membranes (dense intramembranous deposit disease, or DIDD) is associated with variable histologic alterations of the kidneys. We compared clinical features and long-term renal outcome in 21 patients representing two histologic subtypes of DIDD, namely membranoproliferative glomerulonephritis (MPGN) and focal segmental glomerulonephritis (FSGN). We found that MPGN-type DIDD in 12 patients was associated with nephrotic syndrome in 12, persistent hypocomplementemia in 10 and progression to chronic renal insufficiency in 8. In 9 patients with the focal segmental variety of DIDD, nephrotic syndrome was observed in 3, persistent hypocomplementemia in none, and progression to renal insufficiency in 2 (significance: nephrotic syndrome, p = 0.001; persistent hypocomplementemia, p = 0.0001; chronic renal insufficiency, p = 0.02). In one patient transition from focal segmental to MPGN-type DIDD was observed. We conclude that DIDD is a heterogeneous disorder, and that certain clinical and histologic features may be useful in predicting ultimate outcome.

Adolescent↗
PubMed1989

Embryonic expression pattern of a family of Drosophila proteins that interact with a central nervous system regulatory element.

The protein Elf-1 interacts with a cis-acting element that is required specifically for the neuronal expression of the Drosophila dopa decarboxylase gene Ddc. Using protein purified from Drosophila embryos, we raised Elf-1-specific monoclonal antibodies. The expression of Elf-1 during embryogenesis is restricted to nuclei of tissues derived from ectoderm, predominantly the central nervous system (CNS) and the epidermis. Within the CNS, Elf-1 is present in only a small fraction of nuclei, and the pattern of expressing nuclei changes dramatically during development. Elf-1 and Ddc are coexpressed in primary cultures of neural cells. However, we do not detect Elf-1 in Ddc-expressing neurons in vivo, leading to the suggestion that Elf-1 activity is required in vivo for initiation of Ddc expression but not for its maintenance. The antibodies also were used to isolate cDNA clones encoding Elf-1. Alternate forms of Elf-1 mRNA result in at least three protein isoforms.

Amino Acid Sequence↗
PubMed1989

Acne is not associated with abnormal plasma androgens.

Plasma dehydroepiandrosterone sulphate, androstenedione, testosterone (T), dihydrotestosterone (DHT), and sex hormone binding globulin (SHBG) have been measured in 64 females and 26 males aged less than 25 years and with acne vulgaris. Oestradiol was measured in the males. Free T and free DHT were calculated. Acne was graded on three sites and the sebum excretion rate (SER) was measured in most patients. With the possible exception of free DHT, none of the plasma steroids or SHBG correlated with acne severity or with SER. Free DHT in the females showed a possible, but weak, correlation with total acne (r = 0.25, P = 0.07), but comparison with male data showed that this was not causative. The role of androgens in acne is permissive and plasma androgen measurements usually have no place in its management.

Acne Vulgaris↗
PubMed1989

Prune belly syndrome: clinicopathologic study of 29 cases.

The clinical course and the pathologic features of 29 patients with the prune belly syndrome (PBS) are reviewed. There were 26 males and 3 females. In addition to the classical triad of deficient abdominal musculature, urinary tract abnormalities, and cryptorchidism, a broader spectrum of other defects was found including musculoskeletal (58%) and gastrointestinal (31%) abnormalities. Genital anomalies were present in all three female patients. Many of these defects may be inapparent at birth, but are the cause of morbidity and mortality later in life. Severe urinary tract maldevelopment and pulmonary hypoplasia as part of the oligohydramnios syndrome was the most common cause of perinatal deaths. In these patients, major portions of the renal parenchyma were dysplastic, but in survivors, renal dysplasia, when present, was minor by comparison, and affected less than 1/3 of the parenchyma. Although several questions remain unanswered, we believe that the PBS results from the effect of one or more teratogenic agents on the somatic mesoderm, producing inappropriate mesenchymal development and inadequate mesenchymal-epithelial interactions that lead to abnormal development and dilatation of some of its derivatives (abdominal muscles, ureter, bladder, prostate, urethra, and gubernaculum). Although abnormalities in derivatives of the intermediate mesoderm (kidney) may also be produced by the injurious agent(s), they are more likely a result of urinary obstruction. Abnormalities in other organs and systems are the consequence of oligohydramnios.

Abnormalities, Multiple↗
PubMed1988

Effects of dilating the canine pulmonary annulus with two balloons. Doppler ultrasound and postmortem findings.

Simultaneous inflation of two balloons may be necessary for balloon dilation valvuloplasty in patients with a large annulus. We examined the cardiovascular effects of dilating the pulmonary annulus with two balloons in 18 normal dogs using pulsed Doppler ultrasound and gross and microscopic examination. When the ratio of the cross-sectional area (CSA) during dilation to the CSA of the pulmonary annulus was between 1.04 and 1.28, there was valvar regurgitation in only one dog, in which catheter manipulation was complicated by heartworms, and damage was confined to intimal changes. (The dog was killed 24 hours after dilation.) With ratios between 1.67 and 1.76 (equal to the CSA of a single balloon with a diameter 33% greater than the annulus), there was trivial or mild tricuspid or pulmonary regurgitation, and anatomic changes were more prominent but still superficial. Two animals killed after nine days had resolution of valvar regurgitation and healing damage. With CSA ratios greater than 2.00 or with balloon rupture, myocardial damage and laceration of the pulmonary arteries resulted. Simultaneous inflation of two balloons within the right ventricular outflow tract with CSA ratios of up to 1.76 results in minimal cardiovascular trauma.

Animals↗
PubMed1988

Ovarian tumorlike structures, biovular follicles, and binucleated oocytes in children: their frequency and possible pathologic significance.

The occurrence of microscopic gonadoblastomalike and sex cord tumor with annular tubuleslike structures, biovular follicles, and binucleated oocytes was analyzed in 288 ovaries from 222 consecutive pediatric autopsies. Tumorlike structures were identified in 29% of the autopsies studied, biovular follicles were observed in 52%, and binucleated oocytes in 19%. These changes were not observed in 22 ovaries from adults. Sixteen cases with gonadoblastomalike structures were stained immunohistochemically for placental alkaline phosphatase and were nonreactive for this marker. These tumorlike structures and multiovular follicles are probably an expression of abnormal folliculogenesis that apparently disappears as the child matures and should not be confused with true neoplasms. Although these morphologic structures resemble the patterns of specific types of gonadal neoplasms, there is little evidence to suggest any potential for future neoplastic transformation.

Adolescent↗
PubMed1988

Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation.

B cell lymphoproliferative disorders (BLPD) developed in eight patients following bone marrow transplantation (BMT) for leukemia (five patients) or immunodeficiency (three patients). Recipients of T depleted marrow from a mismatched donor were at particularly high risk of this complication. Six of 25 (24%) recipients of mismatched T depleted bone marrow developed BLPD. In contrast, none of 47 matched T depleted transplants, one of ten (10%) who received non-depleted marrow from an unrelated donor, and only one of 424 matched non-depleted transplants were associated with BLPD. Epstein-Barr virus (EBV) specific serology and DNA hybridization studies demonstrating five to 50 copies of EBV genome/cell in involved tissues implicate this virus as an associated etiologic agent. Restriction fragment length polymorphism (RFLP) and cytogenetic analysis of involved tissue demonstrated donor origin (five of seven) or host origin (two of seven). Histologic appearance was similar to EBV-induced polymorphic B cell proliferations described following solid organ transplantation, or which occur de novo in primary immunodeficiency. Six of seven patients with adequate tissue available for study were found to have monoclonal proliferations by: in situ immunofluorescence (six of seven), and/or immunoglobulin gene rearrangement, (four of six). Cytogenetic analysis of involved tissues from four patients showed a normal karyotype, whereas two had multiple clonal chromosomal abnormalities. Seven patients died despite aggressive attempts at therapy with combinations of antiviral, immunologic, and chemotherapeutic agents.

Antibodies, Viral↗
PubMed1987

Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B.

The nuclear lamina in adult mammalian somatic cells is composed of three major proteins, lamins A, B, and C. The expression of these proteins during the differentiation of teratocarcinomas and mouse embryogenesis is described. Embryos up to day 8 of gestation and embryonal carcinoma (EC) cells express only a single lamin species closely resembling, if not identical to, lamin B. Lamins A and/or C were detected in fertilized eggs, but disappear during the first 2-4 cleavage divisions, only reappearing in 8 day post-implantation embryos. These two lamins are absent from EC cells, but are strongly expressed in some of their derivatives. These results show that cells of the early mouse embryo do not have a functional requirement for lamins A and C and imply that the structural organization of the nucleus may change fundamentally during embryogenesis.

Animals↗
PubMed1987

Accumulation of adrenocorticotropin secretory granules in the midbody of telophase AtT20 cells: evidence that secretory granules move anterogradely along microtubules.

During the cell cycle the distribution of the ACTH-containing secretory granules in AtT20 cells, as revealed by immunofluorescence labeling and electron microscopy of thin sections, undergoes a cycle of changes. In interphase cells the granules are concentrated in the Golgi region, where they form, and also at the tips of projections from the cells, where they accumulate. These projections contain many microtubules extending to their tips. During metaphase and anaphase the granules are randomly distributed in the cytoplasm of the rounded-up mitotic cells. On entry into telophase there is a rapid and striking redistribution of the granules, which accumulate in large numbers in the midbody as it develops during cytokinesis. This accumulation of secretory granules in the midbody is dependent upon the presence of microtubules. The changing pattern of distribution of the secretory granules during the cell cycle fulfills the predictions of a model envisaging first that secretory granules associate with and move along interphase microtubules in a net anterograde direction away from the centrioles, and secondly that they do not associate with microtubules of the mitotic spindle during metaphase and anaphase.

Adrenocorticotropic Hormone↗
PubMed1987

An antibody specific for an endoproteolytic cleavage site provides evidence that pro-opiomelanocortin is packaged into secretory granules in AtT20 cells before its cleavage.

We have raised a rabbit antiserum against a synthetic peptide corresponding to the cleavage site between beta-lipotropic hormone and the ACTH moieties of murine pro-opiomelanocortin (POMC). After affinity purification, the anti-cleavage site antibody immunoprecipitates POMC from extracts of AtT20 cells but it does not immunoprecipitate the ACTH in such extracts or any of the other products of cleavage of POMC. By contrast, an antiserum raised against pure swine ACTH immunoprecipitates both POMC and ACTH from AtT20 cell extracts. Using the anti-cleavage site antibody we have shown that all the POMC synthesized during a 15-min pulse-labeling with [35S]methionine is cleaved at this site within 1 h. By immunoelectron microscopy we show that approximately 25-30% of peripheral secretory granules in AtT20 cells can be labeled with the anti-cleavage site antibody while anti-ACTH antiserum labels all these granules. This establishes that at least some POMC is packaged into secretory granules before its proteolytic cleavage.

Adrenocorticotropic Hormone↗