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M J O'Brien

Publications and source records attributed to M J O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fine-needle aspiration cytology diagnosis of colloid nodule versus follicular variant of papillary carcinoma of the thyroid.

The cytologic differential diagnosis of colloid nodule (CN) and the follicular variant of papillary carcinoma (FVPC) is difficult with common morphologic features. To assess the utility of 18 cytologic morphometric parameters in the diagnosis of these thyroid lesions we evaluated 31 FNA samples that had histologic confirmation of the diagnoses. These 31 cases included 15 cases of CN, 8 cases of FVPC, and 8 cases of the usual variant of papillary carcinoma (UVPC) for reference values. For the morphometric analysis we used an Optimas 4.0 image analysis system. Comparing the CN group with the UVPC group revealed that eight of the parameters had statistically significant differences. The UVPC specimens were more cellular, less cohesive, had presence of papillary cellular groups more frequently, larger nuclei (UVPC: 109.33 +/- 30.19 microns2; CN: 66.81 +/- 15.02 microns2), higher nuclear to cytoplasmic (N/C) ratio, larger nucleoli, and present nuclear grooves and nuclear pseudoinclusions more frequently. The FVPC group differed from the CN group only in three parameters which included larger nuclei (98.49 +/- 18.24 microns2), higher N/C ratio, and a more frequent presence of nuclear pseudoinclusions. When we compared these two variants of papillary carcinoma, we found that the UVPC specimens had less cellular cohesion, less preservation of the architectural polarity and a more frequent presence of papillary cellular groups than the FVPC. The FVPC can be differentiated from CN based on nuclear changes, which included a larger size, higher N/C ratio, and presence of pseudoinclusions. The absence of cellular cohesion and polarity combined with the presence of papillary groups are useful in separating the UVPC from the FVPC. A cutoff of 75 microns2 should be used in separating benign from malignant nuclei.

Biopsy, Needle↗
PubMed1998

Factors affecting the developmental competence of mouse oocytes grown in vitro: follicle-stimulating hormone and insulin.

This study was undertaken to test the hypothesis that FSH treatment of cultured oocyte-granulosa cell complexes promotes acquisition of competence to complete preimplantation embryo development. Oocyte-granulosa cell complexes were isolated from the preantral follicles of 12-day-old mice and cultured for 10 days in serum-free medium, supplemented with insulin (5 microgram/ml), transferrin (5 microgram/ml), and selenium (5 ng/ml) and containing a highly potent preparation of FSH (0-5 ng/ml). Oocytes were matured and fertilized in vitro and embryos cultured to determine the frequency of development to the blastocyst stage. There was no effect of FSH on oocyte size, general morphology, or competence to resume meiosis. However, addition of FSH to medium containing insulin had a deleterious effect on the percentage of mature oocytes competent to develop to the blastocyst stage. Deletion of insulin from the medium for culture of oocyte-granulosa cell complexes prevented the deleterious effect of FSH, but FSH still did not promote acquisition of competence to complete preimplantation development. Culture of oocyte-granulosa cell complexes with FSH resulted in elevated expression of LH receptor (LHR) mRNA by granulosa cells and stimulated the production of functional LHRs, whether or not insulin was present. However, FSH-induced expression of LHR mRNA reached a maximum steady-state level by 4 days of culture in the presence of insulin, but this level was not reached until 10 days of culture without insulin. Granulosa cells encompassing growing mouse oocytes in vivo do not express LHR mRNA. Thus, expression of LHR mRNA by granulosa cells closely associated with growing oocytes in vitro indicates inappropriate or ambiguous development. In conclusion, conditions occurring during oocyte growth can have profound detrimental effects on oocyte developmental competence to complete preimplantation development, even when oocyte growth, general morphology, and competence to resume meiosis appear unaffected.

Animals↗
PubMed1997

Uptake and salvage of hypoxanthine mediates developmental arrest in preimplantation mouse embryos.

Preimplantation mouse embryos become arrested after first or second cleavage when cultured in hypoxanthine-supplemented Whitten's medium. We present evidence that the hypoxanthine-induced arrest is dependent on uptake and salvage of hypoxanthine and depletion of phosphoribosylpyrophosphate (PRPP) levels. Hypoxanthine uptake increased during the 2-cell stage and was augmented by glucose. HPLC analysis of [14C]hypoxanthine metabolism revealed that hypoxanthine was salvaged and converted to ATP and guanosine triphosphate (GTP), with a shift to more guanyl nucleotide production at the 3- to 4-cell stage. In embryos from mice with a null mutation for the salvage enzyme hypoxanthine-guanine phosphoribosyltransferase, hypoxanthine did not block development nor was it taken up by the embryos. Glucose, which is required for the hypoxanthine-induced arrest, produced a 5.3-fold increase in PRPP levels at the 2-cell stage, which was eliminated by hypoxanthine. We conclude that metabolism of hypoxanthine to nucleotides mediates its inhibitory action on preimplantation mouse embryos via negative feedback on PRPP synthetase, ultimately resulting in decreased PRPP availability and arrest of other PRPP-dependent pathways. Finally, reversal of the block by EDTA and cAMP-elevating agents may be mediated by alterations in hypoxanthine or glucose uptake, or by changes in the relative metabolism of hypoxanthine.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Topoisomerase II alpha expression in normal, inflammatory, and neoplastic conditions of the gastric and colonic mucosa.

Topoisomerase II alpha (TP) excises and reconnects double-stranded super-coiled DNA during the replicative cell cycle. We studied the localization of TP and Ki-67 in inflammatory and neoplastic mucosal lesions of the stomach and of TP in similar conditions of the colon. TP expression was correlated with tumor stage, grade, and survival time in the colonic tumors to evaluate its potential utility as a predictive marker for clinical outcome. Forty-three sections of chronic gastritis, lesions indefinite for dysplasia, low- and high-grade dysplasia, and gastric adenocarcinomas were immunostained with antibody against TP and Ki-67. For the colon, 71 sections of normal mucosa, chronic colitis, hyperplastic polyps, adenomas, and carcinomas were examined; fresh tissue was analyzed by flow cytometry. Expression of TP in non-neoplastic gastric mucosa was maximal in neck/foveolar cells and focal in surface and deep gland cells. Increased surface and deep gland positivity was found in low-grade dysplasia and a diffuse distribution of positive cells in high-grade dysplasia and carcinoma. The Ki-67 staining pattern was similar. TP in non-neoplastic colon was restricted to the lower crypt zone; it was greatly expanded in the surface/upper crypt region in adenomas and was diffuse in carcinomas. Flow cytometric analysis revealed TP expression mainly in the S and G2/M phase, with higher labeling index in tumors. There was no correlation of TP with stage, grade, or survival times in the colonic tumors. Staining for TP and Ki-67 might help in the distinction of inflammatory and neoplastic lesions of the stomach and colon.

Antigens, Neoplasm↗
PubMed1997

Oocyte control of granulosa cell development: how and why.

Interaction between oocytes and granulosa cells is complex and involves both gap junctions and paracrine signalling factors. Oocyte development in antral follicles is highly dependent on communication with cumulus cells, a subset of granulosa cells that is intimately associated with oocytes. Cumulus cells express characteristics distinct from the mural granulosa cells of preovulatory follicles. The thesis of this paper is that, without the influence of oocytes, the pathway of granulosa cell differentiation in antral follicles leads to the establishment of the mural granulosa cell phenotype. Oocytes in antral follicles abrogate that pathway of granulosa cell differentiation and promote the development of the cumulus cell phenotype. Oocytes may do this in order to control their own microenvironment by regulating differentiation of the supporting cells that are in direct communication with them. Possibly, some aspects of the mural granulosa cell phenotype are antagonistic to, or insufficient for, supporting the final stages of oocyte development. We present evidence that oocytes control their environment by suppressing differentiation of the mural granulosa cell phenotype and promoting differentiation of the cumulus cell phenotype. They achieve this suppression via the secretion of labile paracrine signalling factors. Errors in this regulatory mechanism, whether instigated by defects in the production of oocyte-derived ligands or granulosa cell responses to them, may result in the production of oocytes unable to undergo embryo development or that undergo abnormal follicular development.

Cell Differentiation↗
PubMed1996

Risk of colorectal cancer in the families of patients with adenomatous polyps. National Polyp Study Workgroup.

BACKGROUND: The adenoma-adenocarcinoma sequence in colorectal cancer suggests an increased risk of colorectal cancer in the families of patients with adenomatous polyps. METHODS: A random sample of participants in the National Polyp Study who had newly diagnosed adenomatous polyps were interviewed for information on the history of colorectal cancer in their parents and siblings. The risk of colorectal cancer in family members was analyzed according to the characteristics of the patients with adenomas and in comparison with a sample of patients' spouses, who served as controls. RESULTS: Among the patients with adenomas, 1199 provided information on whether they had a family history of colorectal cancer. After the exclusion of families for which information was incomplete and of 48 patients who had been referred for colonoscopy solely because they had a family history of colorectal cancer, there were 1031 patients with adenomas, 1865 parents, 2381 siblings, and 1411 spouse controls. The relative risk of colorectal cancer, adjusted for the year of birth and sex, was 1.78 for the parents and siblings of the patients with adenomas as compared with the spouse controls (95 percent confidence interval, 1.18 to 2.67). The relative risk for siblings of patients in whom adenomas were diagnosed before 60 years of age was 2.59 (95 percent confidence interval, 1.46 to 4.58) as compared with the siblings of patients who were 60 or older at the time of diagnosis and after adjustment for the sibling's year of birth and sex and a parental history of colorectal cancer. The risk increased with decreasing age at the time of the diagnosis of adenoma (P for trend < 0.001). The relative risk for the siblings of patients who had a parent with colorectal cancer, as compared with those who had no parent with cancer, was 3.25 (95 percent confidence interval, 1.92 to 5.52), after adjustment for the sibling's year of birth and sex and the patient's age at diagnosis. CONCLUSIONS: Siblings and parents of patients with adenomatous polyps are at increased risk for colorectal cancer, particularly when the adenoma is diagnosed before the age of 60 or--in the case of siblings--when a parent has had colorectal cancer.

Adenomatous Polyps↗
PubMed1996

Factors influencing outcome of surgery for primary aldosteronism.

OBJECTIVE: To identify factors that influence the outcome of surgery for primary aldosteronism. DESIGN: A retrospective clinical series, with a mean follow-up of 106 months (range, 12-280 months), of 42 patients who underwent adrenalectomy for primary aldosteronism between the years 1970 and 1993. SETTING: All patients were operated on at the Boston University Medical Center Hospital. PATIENTS AND INTERVENTION: We reviewed the records of 22 women and 20 men, ranging in age from 25 to 68 years, who underwent adrenalectomy for primary aldosteronism. Tests performed for preoperative classification of the adrenal pathological abnormalities included adrenal venous sampling, postural stimulation test, iodocholesterol I 131 scintigraphy, and computed tomography. MAIN OUTCOME MEASURES: The surgical outcome was classified as follows: response, normal blood pressure measurement (< 160/95 mm Hg) without medication; incomplete response, normal blood pressure measurement with medication or blood pressure measurement greater than 160/95 mm Hg despite antihypertensive treatment. RESULTS: Twenty-five patients (60%) became normotensive following surgery. The following factors were associated with a complete response to adrenalectomy by univariate analysis: adenoma classification (odds ratio [OR] = 9.6, P = .002); preoperative response to spironolactone (OR = 8.3, P = .007); age younger than 44 years (OR = 6.2, P = .009); and duration of hypertension less than 5 years (OR = 5.1, P = .03). Response to spironolactone was predictive only in cases classified as adenoma (P = .004). Duration of hypertension showed a strong correlation with age (r = 0.62). Using stepwise logistic regression, adenoma pathological classification, response to spironolactone, and duration of hypertension less than 5 years contributed independently to a predictive model. Micronodular hyperplasia alone was associated with incomplete response. The presence of coexisting micronodular hyperplasia in patients with adenoma did not affect the odds for a complete response. Computed tomography for preoperative diagnosis of adenoma showed the same level of accuracy (75%) as that for postural stimulation test and iodocholesterol scintigraphy, but less than that for adrenal venous sampling (91%). CONCLUSIONS: The study showed that the main determinants of a surgical cure of hypertension in primary aldosteronism were presence of adenoma and preoperative response to spironolactone. We favor computed tomography as the initial test to establish preoperative diagnosis of adenoma because of its reproducibility and high specifity.

Adenoma↗
PubMed1996

Development in vitro of mouse oocytes from primordial follicles.

The objective of these studies was to achieve complete oocyte development in vitro beginning with the oocytes in the primordial follicles of newborn mouse ovaries. A two-step strategy was developed: first the ovaries of newborn mice were grown in organ culture for 8 days, and then the developing oocyte-granulosa cell complexes were isolated from the organ-cultured ovaries and cultured for an additional 14 days. The oocytes of primordial follicles are approximately 4190 microns3 in volume (20 microns in diameter), and this volume increased by approximately 53,810 microns3 to a final size of 58,000 microns3--a 13.8-fold increase--during the 8 days of organ culture. In the first experiment the oocyte-granulosa cell complexes were grown in control medium or in medium supplemented with FSH (0.5 ng/ml), epidermal growth factor (EGF; 1.0 ng/ml), or EGF plus FSH. Only 50-60% of the complexes cultured in control medium or in medium supplemented with FSH were recovered at the end of the 14-day culture period. In contrast, more than 90% of the complexes cultured in medium supplemented with EGF were recovered. The median size of the oocytes grown in control medium was 176,800 microns3 (69-microns diameter), while the median size of those grown in medium supplemented with EGF was slightly smaller (136,400-microns3 volume; 63-microns diameter), due to the survival of more smaller-size oocytes in EGF-containing medium. Thirty percent of the oocytes recovered after development in FSH-containing medium were competent to undergo germinal vesicle breakdown (GVB). In the second set of experiments, oocyte-granulosa cell complexes isolated from organ-cultured ovaries were cultured in medium supplemented with either 0.5 or 5.0 ng/ml FSH or with these same concentrations of FSH plus 1.0 ng/ml EGF. Again, increased oocyte recovery was observed in the groups cultured with EGF. There was no difference among the groups in the percentage of the oocytes that acquired competence to undergo GVB (32%) or in the percentage of GVB oocytes that produced a polar body, thus indicating progression of meiosis to metaphase II (22%). When the mature oocytes were inseminated, 21% underwent fertilization and cleavage to the 2-cell stage in the groups without EGF during oocyte development, while 42% underwent fertilization and cleavage to the 2-cell stage in the groups cultured with EGF. Less than 2% of the 2-cell-stage embryos developed to the blastocyst stage in any of the groups. One hundred and ninety 2-cell-stage embryos were transferred to the oviducts of pseudopregnant females; two females produced one pup each; one was living and the other had apparently died recently. The results reported here clearly show that complete development of oocytes in vitro from the primordial follicle stage is possible and establish the framework for further studies using oocytes from laboratory animals as model systems for the development of oocytes from humans as well as from animals of agricultural and zoological importance.

Animals↗
PubMed1996

The adenoma-carcinoma sequence in colorectal neoplasia.

In this article the epidemiologic, pathologic, molecular, and clinical evidence for the adenoma-carcinoma sequence is reviewed. The authors describe the morphologic evolution of the precursor adenomas, from the earliest discernible abnormality of the colon to adenomas with advanced pathologic features, the factors that determine the risk of progression of adenomas to adenocarcinoma, the molecular events that parallel or underlie the morphologic changes, the outcome of clinical interventions that have tested this hypothesis, and the time frame within which this progression is likely to occur.

Adenocarcinoma↗
PubMed1996

Postmortem evaluation of homotypic variation in shoe characteristics of 201 thoroughbred racehorses.

OBJECTIVES: To develop a standard technique for evaluation of racehorse shoes, to assess homotypic variation (interlimb variation) in shoe characteristics, and to determine whether shoe characteristics varied with age and sex. DESIGN: Cross-sectional study. ANIMALS: Thoroughbred racehorses (n = 201) that died or were euthanatized at California racetracks between August 1992 and July 1994. PROCEDURE: Shoe characteristics were measured on horses examined after death. Percentage of agreement was used to compare shoe characteristics between limbs (homotypic variation). Using chi 2 analysis, shoe characteristics were compared between horses grouped by age and sex. RESULTS: Toe grabs were present on 90.5% of horses, and rim shoes were present on 15.9% of horses. Heel traction devices were less frequent on front (2.5%) than rear (6%) hooves. Pads were present on 24.9% of horses, with bonded rim pads most common. Special types of shoes were present cn 5% of horses. Percentage of agreement between left and right front hooves and between left and right rear hooves was high (20/25 variables; % agreement > or = 99). In contrast, percentage of agreement between left front and left rear hooves and between right front and right rear hooves was low (2/25 variables; % agreement > or = 99). Presence of a pad was significantly (P < 0.05) associated with age, and several shoe variable (size, presence of a special shoe, overall wear matched) were significantly (P < 0.05) associated with sex. CLINICAL RELEVANCE: Except for variables related to special shoes, wear, and weight, 1 shoe for the respective fore- or hind limbs could be used as an indicator for the contralateral shoe worn by Thoroughbred racehorses without substantial loss of information. However, 1 shoe could not be used as an indicator for shoe characteristics of all 4 limbs. Some shoe characteristics are associated with age and sex, and these variables should be considered possible confounders in studies of shoe characteristics.

Animals↗
PubMed1996

Digital imaging in anatomic pathology.

Advances in computer technology continue to bring new innovations to departments of anatomic pathology. This article briefly reviews the present status of digital optical imaging, and explores the directions that this technology may lead over the next several years. Technical requirements for digital microscopic and gross imaging, and the available options for image archival and retrieval are summarized. The advantages of digital images over conventional photography in the conference room, and the usefulness of digital imaging in the frozen section suite and gross room, as an adjunct to surgical signout and as a resource for training and education, are discussed. An approach to the future construction of digital histologic sections and the computer as microscope is described. The digital technologic applications that are now available as components of the surgical pathologist's workstation are enumerated. These include laboratory information systems, computerized voice recognition, and on-line or CD-based literature searching, texts and atlases and, in some departments, on-line image databases. The authors suggest that, in addition to these resources that are already available, tomorrow's surgical pathology workstation will include network-linked digital histologic databases, on-line software for image analysis and 3-D image enhancement, expert systems, and ultimately, advanced pattern recognition capabilities. In conclusion, the authors submit that digital optical imaging is likely to have a significant and positive impact on the future development of anatomic pathology.

Humans↗
PubMed1995

Detection of p21ras mutations in colorectal adenomas and carcinomas by enzyme-linked immunosorbent assay.

BACKGROUND: Point mutations of the ras protooncogene, primarily within codons 12 and 13, are commonly identified in colorectal carcinomas and large adenomas. Despite data suggesting that ras genotyping may have clinical significance with respect to colorectal cancer screening and prognosis, more widespread use has been limited because of the lack of a suitable assay system. The principal objective of this study was to assess the feasibility and validity of a qualitative enzyme-linked immunosorbent assay (ELISA) for detecting the four most common ras mutations in human colorectal tumors at the protein (p21ras) level. METHODS: Tissue homogenates (11-121 micrograms) from endoscopically or surgically resected colorectal adenomas, carcinomas, and normal mucosae were evaluated by a commercially available ELISA (Oncogene Science, Inc. Cambridge, MA) for mutant p21ras containing arginine position 12 (arg12), valine position 12 (val12), aspartate position 12 (asp12), and aspartate position 13 (asp13) amino acid substitutions. Portions of the same tissue from an initial series of 27 specimens also were subjected to mutant-enriched polymerase chain reaction (PCR) and/or PCR amplification with subsequent DNA sequence analysis to validate the ELISA data. RESULTS: Forty-seven adenomas, 9 carcinomas, and 14 normal mucosae were assayed. Mutations were identified in 16 (34%) of the adenomas (7-asp12, 7-val12, 2-asp13), 3 (33%) of the carcinomas (1-asp12, 1-arg12, 1-asp13), and none of the normal mucosae by ELISA: Polymerase Chain Reaction and DNA sequencing analyses demonstrated identical results for 21 of the 23 (91%) and 14 of 16 (88%) homogenates tested, respectively. The ELISA demonstrated an overall sensitivity of 80-86%, specificity of 90-92%, positive predictive value of 86-100%, and negative predictive value of 86-91%. CONCLUSIONS: The ELISA is a feasible and valid approach for identifying p21ras mutations in human colorectal adenomas and carcinomas.

Adenoma↗
PubMed1995

Building a new health system: implications for public health management and practice.

Changes in the health care system should encourage private-sector health care providers and the public health system to work in partnership to improve the public health of all citizens. Minnesota, with its recent comprehensive health reform efforts, has made a strong commitment to strengthen the public health system in performing those functions that are critical to protecting the health of the public and meeting public health goals that are identified by the state and local communities.

Community Health Services↗
PubMed1995

Prevention of colorectal cancer: guidelines based on new data. WHO Collaborating Center for the Prevention of Colorectal Cancer.

Recently published good quality data are the basis for this update. The newly reported studies include randomized trials, non-randomized cohort studies, and case-control studies; some of the data had mortality reduction as the endpoint. These guidelines, which were developed by the WHO Collaborating Center for the Prevention of Colorectal Cancer at Memorial Sloan-Kettering Cancer Center in conjunction with an International Advisory Committee, include primary prevention, screening of average-risk individuals, screening of individuals with heritable factors for colorectal cancer, surveillance of patients with colorectal polyps, and surveillance of patients with chronic ulcerative colitis. A list of papers reviewed for this update are cited, including recently published trials evaluating faecal occult-blood testing, case-control studies of sigmoidoscopy, the National Polyp study, and familial colon cancer studies. These guidelines will help inform patients and guide physicians in their approach to the prevention of colorectal cancer.

Colorectal Neoplasms↗
PubMed1995

Correlation of teichoic acid D-alanyl esterification with the expression of methicillin resistance in Staphylococcus aureus.

Methicillin-susceptible and -resistant isolates of Staphylococcus aureus, including a teichoic acid-deficient mutant, were examined under varying physiological conditions for their degree of teichoic acid and lipoteichoic acid D-alanyl esterification. Methicillin-resistant strains grown in the presence of methicillin and NaCl possessed significantly decreased amounts of D-alanyl ester when compared with methicillin-susceptible isolates. These strains also exhibited reduced autolysis. An autoradiographic procedure was used to detect mutants, isolated by Tn917 and nitrosoguanidine mutagenesis of methicillin-susceptible strains, which were defective in D-alanyl ester formation. The quantitative uptake of D-[14C]alanine in these mutants was determined and the effect of methicillin on the growth and viability of each mutant was compared with the wild-type strain. S. aureus mutant strains, defective in the uptake and incorporation of D-alanine, were shown to exhibit slightly reduced autolysis and an enhanced expression of methicillin resistance.

Alanine↗
PubMed1993

Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.

BACKGROUND: The current practice of removing adenomatous polyps of the colon and rectum is based on the belief that this will prevent colorectal cancer. To address the hypothesis that colonoscopic polypectomy reduces the incidence of colorectal cancer, we analyzed the results of the National Polyp Study with reference to other published results. METHODS: The study cohort consisted of 1418 patients who had a complete colonoscopy during which one or more adenomas of the colon or rectum were removed. The patients subsequently underwent periodic colonoscopy during an average follow-up of 5.9 years, and the incidence of colorectal cancer was ascertained. The incidence rate of colorectal cancer was compared with that in three reference groups, including two cohorts in which colonic polyps were not removed and one general-population registry, after adjustment for sex, age, and polyp size. RESULTS: Ninety-seven percent of the patients were followed clinically for a total of 8401 person-years, and 80 percent returned for one or more of their scheduled colonoscopies. Five asymptomatic early-stage colorectal cancers (malignant polyps) were detected by colonoscopy (three at three years, one at six years, and one at seven years). No symptomatic cancers were detected. The numbers of colorectal cancers expected on the basis of the rates in the three reference groups were 48.3, 43.4, and 20.7, for reductions in the incidence of colorectal cancer of 90, 88, and 76 percent, respectively (P < 0.001). CONCLUSIONS: Colonoscopic polypectomy resulted in a lower-than-expected incidence of colorectal cancer. These results support the view that colorectal adenomas progress to adenocarcinomas, as well as the current practice of searching for and removing adenomatous polyps to prevent colorectal cancer.

Adenocarcinoma↗