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Biomedical subjects

R C Bentley

Publications and source records attributed to R C Bentley.

53 records · Page 3Linked to original sources

Epithelial repair of the uterine cervix: assessment of morphologic features and correlations with cytologic diagnosis.

This study evaluates the morphologic features of squamous epithelial repair of the uterine cervix, a condition describing a state of regeneration, and compares them with the features of its two histologic mimics, squamous metaplasia and mild dysplasia. The materials examined were from 20 patients with a histologic diagnosis of repair, 42 with cervical biopsy specimens of acceptable quality obtained within 3 weeks of a cervical smear showing repair, and 20 each with squamous metaplasia or mild dysplasia. Specimens with repair disclosed distinctive morphologic characteristics. On low-power magnification, the stroma was chronically inflamed (100%), often floridly (55%). The nuclei were uniform with absent or minimal pleomorphism (90%). The chromatin was bland and evenly distributed (70%). Nucleoli of a bull's eye or macronucleolar appearance (45%) were easily found. Mildly dysplastic epithelium, unlike reparative epithelium, was infrequently associated with an intensely inflamed stroma (20%); its nuclei were pleomorphic (100%) and commonly displayed coarse chromatin (75%) and mitoses (60%). Metaplastic epithelium ws also infrequently associated with an intensely inflamed stroma (10%). Nuclear pleomorphism (10%) and mitotic figures were infrequent (10%), never atypical (0%), and always basally located. Most nuclei had nucleoli, but the majority were small (80%). This study indicates that most cases of repair, mild dysplasia, and metaplasia can be readily distinguished, although due to overlapping features, some cases are difficult to classify as shown by interobserver variability.

Cell Nucleus↗

Production and characterization of two ependymoma xenografts.

Childhood ependymomas exhibit epidemiologic, anatomic, histologic, and biologic features and distinguish them from other gliomas. Because of their propensity to grow in functionally sensitive regions of the brain, adequate tumor sampling for basic and therapeutic research is limited. We have established xenografts in both subcutaneous and intracranial nude mouse systems (D528 EP-X, D612 EP-X) from the ependymomas of two nonrelated children. Median subcutaneous growth rates (reported in days to grow from 200 mm3 to 1000 mm3) are 82 days for D528 EP-X (n = 10) and 50 days for D612 EP-X (n = 10). D528 EP-X grows intracranially with a median postimplantation survival of 85 days (n = 10); D612 EP produces a median postimplantation survival of 72.5 days (n = 10). Both xenografts grow as well-formed masses with no evidence of infiltration into either brain or subcutaneous tissues. While perivascular pseudopalisading is found in both xenografts, true ependymal rosette formation is absent. Ultrastructurally, neither xenograft exhibits cilia, but both produce abundant intermediate filaments. By light microscopy, the neoplastic cells are immunoreactive for the intermediate filaments glial fibrillary acidic protein, vimentin, and nestin. Karyotypically D528 EP exhibits 46,XX,del(6)(q22q26)/46,XX while D612 EP exhibits 50,XX, +X,t(1;8)(p11;q11),t(1;8)(p11;q11), +1,-4, der(5)t(4;5)(q12;q35), +der(5)t(4;5)(q12;q35),-6, +9, +9,-16, +der(17)t(6;17)(p11;p11), +mar. Restriction fragment length polymorphism studies comparing the primary brain tumor tissue from each patient against multiple passages of the resulting xenografts confirm the origin of both xenografts. These xenografts represent models on which future studies into the oncogenesis, progression and therapy of ependymomas can be performed.

Animals↗

Malignant transformation of the human endometrium is associated with overexpression of lactoferrin messenger RNA and protein.

In the mouse uterus, lactoferrin is a major estrogen-inducible uterine secretory protein, and its expression correlates directly with the period of peak epithelial cell proliferation. In this study, we examine the expression of lactoferrin mRNA and protein in human endometrium, endometrial hyperplasias, and adenocarcinomas using immunohistochemistry, Western immunoblotting, and Northern and in situ RNA hybridization techniques. Our results reveal that lactoferrin is expressed in normal cycling endometrium by a restricted number of glandular epithelial cells located deep in the zona basalis. Two thirds (8 of 12) of the endometrial adenocarcinomas examined overexpress lactoferrin. This tumor-associated increase in lactoferrin expression includes an elevation in the mRNA and protein of individual cells and an increase in the number of cells expressing the protein. In comparison, only 1 of the 10 endometrial hyperplasia specimens examined demonstrates an increase in lactoferrin. We also observe distinct cytoplasmic and nuclear immunostaining patterns under different fixation conditions in both normal and malignant epithelial cells, similar to those previously reported in the mouse reproductive tract. Serial sections of malignant specimens show a good correlation between the localization of lactoferrin mRNA and protein in individual epithelial cells by in situ RNA hybridization and immunohistochemistry. Although the degree of lactoferrin expression in the adenocarcinomas did not correlate with the tumor stage, grade, or depth of invasion in these 12 patients, there was a striking inverse correlation between the presence of progesterone receptors and lactoferrin in all 8 lactoferrin-positive adenocarcinomas. In summary, lactoferrin is expressed in a region of normal endometrium known as the zona basalis which is not shed with menstruation and is frequently overexpressed by progesterone receptor-negative cells in endometrial adenocarcinomas.

Adenocarcinoma↗

Anaplastic renal cell carcinoma following neuroblastoma.

Renal cell carcinoma is unusual in children. We report a case of anaplastic renal cell carcinoma arising in a 7-year-old girl following treatment for Stage III neuroblastoma. The renal cell carcinoma has unusual histologic and ultrastructural features, which are discussed. The case is further unusual in that few children with advanced stage neuroblastoma survive long enough to develop second malignant neoplasms.

Anaplasia↗

Villoglandular adenocarcinoma of the cervix: a case report.

BACKGROUND: Villoglandular adenocarcinoma of the cervix is a rare neoplasm associated with a favorable outcome and has not been described as a complication of pregnancy. CASE: A gravida at 20 weeks' gestation was found to have a bulky stage-IB adenocarcinoma of the cervix. She was delivered at 32 weeks' gestation by cesarean, then a radical hysterectomy and pelvic and periaortic lymphadenectomies were performed. Pathology revealed a deeply invasive, grade 1 villoglandular adenocarcinoma confined to the cervix. The patient remains free of disease at 14 months follow-up. CONCLUSION: Villoglandular adenocarcinoma of the cervix has a favorable prognosis and can be managed conservatively, even when complicated by pregnancy.

Adenocarcinoma↗

Endometrioid carcinoma of the endometrium with sertoliform differentiation.

Ovarian endometrioid tumors with areas mimicking sex cord-stromal tumors are well documented in the literature, but it is unclear whether a similar tumor occurs in the endometrium. We report here a patient with an endometrial endometrioid adenocarcinoma resembling a Sertoli cell tumor. Immunohistochemical and ultrastructural investigations proved it was an adenocarcinoma rather than a true sex cord-stromal tumor. The features of the endometrial tumor were similar to those described in ovarian endometrioid tumors mimicking sex cord-stromal tumors and we compare them to true sex cord-stromal cell tumors. This case confirms that endometrioid adenocarcinoma with sertoliform differentiation can arise in the endometrium as well as in the ovary.

Adenocarcinoma↗

Papillary carcinoma of the breast: imaging findings.

Papillary carcinoma is a rare malignant tumor of the breast for which the survival rate is better than for most breast carcinomas. Histologically, invasive and in situ forms occur; the in situ form can extend throughout a ductal system (intraductal) or can be confined within a cystic structure (intracystic). Invasive papillary carcinoma can spread from either of the in situ forms but spreads more commonly from the intracystic type. Many reports in the literature have failed to differentiate invasive from in situ papillary carcinomas; similarly, the different mammographic patterns of the two in situ forms of these lesions have not been delineated clearly. Our review of 16 new cases of papillary carcinoma showed a frequent correlation between the histologic types and the mammographic appearance. The intraductal in situ form usually was characterized by clustered microcalcifications. The intracystic in situ type was associated with well-circumscribed masses on mammograms; these masses often were complex on sonograms. The purpose of this essay is to illustrate the mammographic and sonographic features of the histologic varieties of papillary carcinoma. Color Doppler sonograms and MR images of intracystic and invasive tumors also are included.

Aged↗

Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes.

Malignant lymphoma of the testis occurs bilaterally more often than any other tumor type. We report the case of a 62-year-old man who presented with synchronous, bilateral, testicular malignant lymphomas without clinical or radiologic evidence of extratesticular disease. The patient received no therapy other than bilateral orchiectomy and subsequently developed widespread disease 6 months later. Southern blot DNA analysis was performed on the initial orchiectomy samples for immunoglobulin (Ig) gene rearrangements. These genotypic analyses showed different clonal rearrangements in the Ig heavy chain JH region but identical clonal rearrangements in the Ig light chain C Kappa region. To our knowledge this is the first genotypic demonstration of a common clonal origin in synchronous, bilateral, testicular malignant lymphomas. We interpret these findings as molecular evidence that the patient's malignant lymphoma was already disseminated at initial presentation, although it was clinically undetectable at that time.

Antigens, CD↗

Recognition of U1 and U2 small nuclear RNAs can be altered by a 5-amino-acid segment in the U2 small nuclear ribonucleoprotein particle (snRNP) B" protein and through interactions with U2 snRNP-A' protein.

We have investigated the sequence elements influencing RNA recognition in two closely related small nuclear ribonucleoprotein particle (snRNP) proteins, U1 snRNP-A and U2 snRNP-B". A 5-amino-acid segment in the RNA-binding domain of the U2 snRNP-B" protein was found to confer U2 RNA recognition when substituted into the corresponding position in the U1 snRNP-A protein. In addition, B", but not A, was found to require the U2 snRNP-A' protein as an accessory factor for high-affinity binding to U2 RNA. The pentamer segment in B" that conferred U2 RNA recognition was not sufficient to allow the A' enhancement of U2 RNA binding by B", thus implicating other sequences in this protein-protein interaction. Sequence elements involved in these interactions have been localized to variable loops of the RNA-binding domain as determined by nuclear magnetic resonance spectroscopy (D. Hoffman, C.C. Query, B. Golden, S.W. White, and J.D. Keene, Proc. Natl. Acad. Sci. USA, in press). These findings suggest a role for accessory proteins in the formation of RNP complexes and pinpoint amino acid sequences that affect the specificity of RNA recognition in two members of a large family of proteins involved in RNA processing.

Amino Acid Sequence↗

A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein.

We have defined the RNA binding domain of the 70K protein component of the U1 small nuclear ribonucleoprotein to a region of 111 amino acids. This domain encompasses an octamer sequence that has been observed in other proteins associated with RNA, but has not previously been shown to bind directly to a specific RNA sequence. Within the U1 RNA binding domain, an 80 amino acid consensus sequence that is conserved in many presumed RNA binding proteins was discerned. This sequence pattern appears to represent an RNA recognition motif (RRM) characteristic of a distinct family of proteins. By site-directed mutagenesis, we determined that the 70K protein consists of 437 amino acids (52 kd), and found that its aberrant electrophoretic migration is due to a carboxy-terminal charged domain structurally similar to two Drosophila proteins (su(wa) and tra) that may regulate alternative pre-messenger RNA splicing.

Amino Acid Sequence↗

A specific 31-nucleotide domain of U1 RNA directly interacts with the 70K small nuclear ribonucleoprotein component.

We have defined the nucleotide sequence of a protein-binding domain within U1 RNA that specifically recognizes and binds both to a U1 small nuclear ribonucleoprotein component (the 70K protein) and to the previously defined RNA-binding domain of the 70K protein. We have investigated direct interactions between purified U1 RNA and 70K protein by reconstitution in vitro. Thirty-one nucleotides of U1 RNA, corresponding to stem-loop I, were required for this interaction. Nucleotides at the 5' end of U1 RNA that are involved in base pairing with the 5' splice site of pre-mRNA were not required for binding. In contrast to other reports, these findings demonstrate that a specific domain of U1 RNA can bind directly to the 70K protein independently of any other snRNP-associated proteins.

Base Sequence↗

The role of the safety officer.

Unless NHS managers have been testing their nuclear bunkers they will know about the full application to the Crown of the Health and Safety at Work etc. Act 1974 and readers will have noticed an increasing number of safety officer positions being advertised. In this article I would like to look at the role of the district safety officer, his function, objectives and working parameters.

Accident Prevention↗

Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid.

Glucagon, a pancreatic peptide hormone of 29 amino acids that regulates carbohydrate, fat, and protein metabolism, is one of a family of structurally similar regulatory peptides which include GH-releasing hormone, vasoactive intestinal peptide, secretin, and gastric inhibitory peptide. The synthesis of glucagon involves its specific proteolytic cleavage from preproglucagon, a large polyprotein precursor. To facilitate analyses of the cellular processing of pre-proglucagon and to begin studies of the regulation of glucagon gene expression in the rat, we have cloned and sequenced two cDNAs derived from rat neonatal pancreas. The cDNAs represent close to the entire transcriptional sequence of the glucagon gene and encode a pre-proglucagon of 180 amino acids. The coding region of pre-proglucagon contains, in addition to the sequence of glucagon, the sequences of two peptide domains that are related in their structures to glucagon. Glucagon and the two glucagon-like peptides are flanked in the precursor by pairs of basic amino acids characteristic of the sites that are cleaved during the posttranslational processing of pro-hormones. Northern blot analyses indicate the presence of a single mRNA of 1400 +/- 100 nucleotides in the rat pancreas, and results of Southern blotting of rat liver genomic DNA are consistent with the existence of a single chromosomal gene. Comparisons of the nucleotide sequence of the rat pre-proglucagon cDNA with those of the two pre-proglucagons of the anglerfish pancreas encoded by two separate genes indicate that the pre-proglucagon genes probably evolved by intragenic duplications of a DNA segment corresponding to the coding sequences of glucagon and the glucagon-like peptides.

Amino Acid Sequence↗

Human endometrial transforming growth factor-alpha: a transmembrane, surface epithelial protein that transiently disappears during the midsecretory phase of the menstrual cycle.

OBJECTIVES: To characterize the forms of transforming growth factor-alpha (TGF-alpha) in normal human endometrium, to evaluate the regional and temporal changes in TGF-alpha expression, and to correlate the pattern of TGF-alpha expression with physiologic events in the endometrium. METHODS: Immunohistochemistry and Western blot analyses were performed using two TGF-alpha antisera, one raised against the active extracellular N-terminus and the other recognizing the intracellular carboxy terminus of the protein. Immunohistochemistry was performed on hysterectomy specimens from premenopausal women with normal menstrual cycles. Soluble and membrane-bound endometrial proteins were isolated from fresh tissue for Western blot analysis. RESULTS: Antibodies recognizing the intracellular and extracellular domains of TGF-alpha exhibited identical immunohistochemical staining patterns. Transforming growth factor-alpha localized primarily to endometrial epithelial cells, and the most intense staining was in the luminal surface epithelium. In the surface epithelium, TGF-alpha staining was intense in the proliferative phase, decreased during the early secretory phase, was at its nadir in the midsecretory phase, and rebounded in the late secretory phase. Western blot analysis demonstrated two transmembrane forms. The 28-kD protein contained both intracellular and extracellular antigens, and the 18-kD protein contained only the intracellular antigen. CONCLUSION: Western blot data were consistent with the hypothesis that the extracellular segment of TGF-alpha is cleaved from the transmembrane precursor in vivo, as has been demonstrated in other tissues. Immunohistochemistry demonstrated that the TGF-alpha antigens are concentrated in the luminal surface epithelium and decline and disappear in the early to midsecretory phase. These findings suggest that the most active period of membrane-bound TGF-alpha cleavage corresponds with the interval during which preimplantation embryos are in the uterine cavity.

Antibody Specificity↗

Meningioma of the fourth ventricle.

Meningiomas are primary meningeal based tumors of the central nervous system that rarely are located strictly within the fourth ventricle. We report a 72-year-old man operated upon for such a tumor. The pre-operative magnetic resonance images revealed a well circumscribed mass in the fourth ventricle that exhibited a low signal on T1-weighted magnetic resonance images and homogenously enhanced with gadolinium. By light microscopy the tumor was composed of tightly packed spindle cells separated by collagen. Immunohistochemistry showed the tumor cells to be positive for vimentin and epithelial membrane antigen, and negative for glial fibrillary acidic protein. Electron microscopy revealed typical findings of meningioma, including interdigitating cell processes, desmosomes, and intermediate filaments. Although rare, fibroblastic meningioma must be included in the differential diagnosis of a fourth ventricular spindle cell tumor in elderly patients.

Aged↗

Solitary fibrous tumor of the meninges occurring after irradiation of a mixed germ cell tumor of the pineal gland.

Twenty-nine months after surgery, irradiation, and systemic chemotherapy for a pineal mixed germ cell tumor, an 11-year-old Caucasian male developed a 3 cm dural based nodule in the occipital lobe that proved to be a solitary fibrous tumor by immunohistochemical and ultrastructural examination. Differential diagnosis included fibrous meningioma, neurofibroma, Schwannoma, cranial fasciitis of infancy, and solitary fibrous tumor. A Masson trichrome stain revealed a prominent collagenous stroma and reticulin staining exhibited strong pericellular positivity. Immunohistochemical staining demonstrated diffuse vimentin and focal CD34 positivity of tumor cells. Ultrastructural examination revealed fibroblastic differentiation. These features are consistent with solitary fibrous tumor. Although we favor a radiation-induced origin for the neoplasm, alternative explanations for the tumor's origin include cerebrospinal fluid spread from the original germ cell tumor or a de novo neoplasm.

Antineoplastic Agents↗