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Biomedical subjects

M J O'Brien

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

At least 55 records · Page 3Linked to original sources

Carbohydrate dependence during marathon running.

To test the hypothesis that marathon running is dependent on lipid oxidation, 12 post-absorptive males (31.9 +/- 2.1 yr) ran a treadmill marathon and substrate utilization was assessed. Subjects were placed into a fast (F < or = 2 hr, 45 min; 73.3% VO2max), or a slow (S < or = 3 hr, 45 min; 64.5% VO2max) marathon group. The day before testing subjects rested, but ate their normal diet. Subjects were tested in the morning after an overnight fast, and only tap water, at a rate of 1 l.h, was ingested during exercise. Blood glucose concentration rose at exercise onset, peaked at approximately an hour, but then decreased over time remaining at or above resting levels. Free fatty acids and glycerol rose continuously. No significant differences in plasma FFA, glycerol, or blood glucose concentrations were observed between F or S groups during the marathon. Mean blood lactate concentration was significantly higher (P < 0.05) in the F (2.1 +/- 0.3 mM) group than the S (1.2 +/- 0.2 mM) during exercise. Mean plasma epinephrine was significantly higher in the F (0.9 +/- 0.2 ng.ml-1) than the S (0.6 +/- 0.2 ng.ml-1) group; norepinephrine was also higher in F (3.9 +/- 1.4 ng.ml-1) than the S (2.5 +/- 0.9 ng.ml-1, P < or = 0.05). Blood lactate and epinephrine concentrations correlated significantly (4r = 0.76 and 0.78 in F and S groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The National Polyp Study. Design, methods, and characteristics of patients with newly diagnosed polyps. The National Polyp Study Workgroup.

The National Polyp Study (NPS) is a multicenter prospective randomized trial designed to evaluate follow-up surveillance strategies in patients who have undergone polypectomy for the control of large bowel cancer. The study design was developed by a joint research committee from American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the American College of Gastroenterology. Subjects who met the eligibility criteria were randomized into two different treatment arms. Eligibility criteria included: removal of one or more adenomas; complete colonoscopy; no prior polypectomy, inflammatory bowel disease, or familial polyposis; and no history of colon cancer. The treatment arms consisted of a frequent follow-up (1 and 3 years after initial polypectomy) and a less frequent follow-up (3 years). Follow-up examinations included fecal occult blood tests, air-contrast barium enema, and colonoscopy. The latter was done on 9112 referred patients at the seven participating centers from November 1980 until February 1990 who had no history of polypectomy, colon cancer, familial polyposis, or inflammatory bowel disease. Of these patients, 4763 (52.3%) had no polyps; 549 (6.0%) had an invasive cancer; 776 (8.5%) had nonadenomatous polyps; 208 (2.3%) had incomplete examinations; 184 (2.0%) had other findings; and 2632 (28.9%) had one or more adenomas, of which 1418 (53.9%) were randomized to one of the two treatment arms. This article reports the background, rationale, objectives, methods, and organization of this study and includes patient characteristics on initial presentation. Future data provided by the NPS may help in the development of recommendations for surveillance guidelines for such patients. This study also provides a framework to address questions regarding the natural history of adenomas and their relationship with colorectal cancer.

Adenoma↗

Precursors of colorectal carcinoma. Biopsy and biologic markers.

The term biologic marker (biomarker) of colorectal cancer refers in this article to an early preclinical phenotypic characteristic that relates to the risk for developing this cancer. Putative biologic markers in the normal colorectal mucosa of patients at risk include abnormal cell proliferation as determined by kinetic studies, ornithine decarboxylase activity, and polyamine synthesis. Alterations of mucin synthesis have been studied using both histochemical stains and lectin-binding techniques. Blood group and related carbohydrate antigens also have been evaluated as potential biomarkers in the normal mucosa. Biopsy small (less than 5 mm) polyps encountered at endoscopy has become a standard practice. Although a small polyp found to be an adenoma has a low likelihood of harboring high-grade dysplasia or invasive carcinoma, it represents an indicator of risk for colorectal neoplasia. Hyperplastic polyps, however, even though they have certain epidemiologic associations with colorectal neoplasia, are controversial as putative biomarkers of clinical relevance. Current research supports a concept of a field defect of the colorectal mucosa at risk for neoplasia, which may be identified by phenotypic abnormalities of the normal mucosa and the development of small adenomas.

Adenoma↗

Comparison of embryonic developmental competence of mouse oocytes grown with and without serum.

The first objective of this study was to determine whether oocyte growth in serum-free medium affects the solubility of the zona pellucida to alpha-chymotrypsin digestion, which is an index of zona pellucida "hardening" and reflects the potential penetrability of the zona pellucida by sperm. Oocyte-granulosa cell complexes were isolated from the preantral follicles of 12-day-old mice and cultured for 10 days in medium containing 5% fetal bovine serum (FBS) or in serum-free medium. The zonae pellucidae of oocytes grown in serum-free medium were four times as hard as freshly isolated germinal vesicle (GV)-stage oocytes grown in vivo or oocytes grown in vitro in FBS-containing medium. The hardening of the zonae pellucidae of oocytes grown in serum-free medium was prevented by addition of fetuin. The second objective was to compare the competence to undergo embryogenesis of oocytes that grew in serum-free vs. FBS-containing medium. Approximately 70% of the oocytes underwent maturation regardless of whether the medium was serum-free or contained FBS. Of the mature ova grown in medium containing FBS, 53% cleaved to the two-cell stage after insemination compared with only 6% of the ova grown in serum-free medium. Addition of fetuin to the serum-free medium used for oocyte growth increased the frequency of cleavage to the two-cell stage. Of the embryos derived from oocytes that grew in FBS-containing medium, 70% completed the two-cell stage to blastocyst transition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analysis of epithelial and lymphoid phenotypic markers in relation to growth pattern of colorectal adenomas.

The relationship of villous to tubular adenomas is poorly understood and often difficult to characterize morphologically. A villous growth pattern in colorectal adenomas has been associated with a higher frequency of high-grade dysplasia. We compared phenotypic markers using immunoperoxidase techniques in paired samples of villous (75% to 100% villous) and pure tubular adenomas matched for size and degree of dysplasia, which were selected by review of 1,000 polyps from our files. The following monoclonal antibodies were used: CAM 5.2 and AE1/AE3 to cytokeratins; B18, D14, B7.1, and B7.8 to four distinct carcinoembryonic antigen epitopes; Leu-M1 and LN3 to HLA-DR antigen; LN2 to invariant chain class II major histocompatibility complex; LN1 and MB2 to B-cell markers; UCHL1 and MT1 to T-cell markers; Leu-7 to natural killer cells; Mac 387 to macrophages; S-100 to Langerhans-type cells; and a polyclonal antibody to secretory component. LN3 reactivity correlated with villous morphology and secretory component correlated with tubular morphology. Combined HLA-DR and secretory component expression discriminated between tubular and villous growth patterns in 12 of 15 pairs of adenomas (P less than .001). LN2 was expressed more frequently than LN3, but did not correlate with growth pattern. Neuroendocrine cells (Leu-7) were more frequent in tubular adenomas. Carcinoembryonic antigen epitopes did not relate to growth pattern. We did not confirm previously reported differences in cytokeratin expression. We concluded that among the markers tested, HLA-DR expression, which may have an immunologic basis, is most characteristic of colorectal adenomas that exhibit a villous growth pattern.

Adenoma↗

Developmental capacity of mouse oocytes matured in vitro: effects of gonadotrophic stimulation, follicular origin and oocyte size.

Development of mammalian oocytes is usually correlated with ovarian follicular development. This correlation was tested by determining whether gonadotrophic stimulation of follicular development in immature mice resulted in a coordinated increase in the embryonic developmental capacity of the oocytes. Oocyte cumulus cell complexes were isolated at the germinal vesicle stage from small, medium and large antral follicles of 26-day-old mice and matured and fertilized in vitro. The frequency with which embryos from oocytes from small follicles completed the two-cell to blastocyst transition was lower than for embryos from oocytes from large follicles (33% and 79%, respectively). Germinal-vesicle stage oocyte-cumulus cell complexes were isolated from 22-26-day-old mice that were unprimed or primed by injection of equine chorionic gonadotrophin 48 h before isolation. Oocytes were matured in control medium, or in medium containing 1 microgram follicle-stimulating hormone (FSH) ml-1, and then fertilized in vitro. Priming did not increase the number of embryos completing the two-cell stage to blastocyst transition in the 22-day-old group nor did FSH treatment of maturing oocytes when the oocytes were isolated from unprimed 22-day-old mice. In contrast, priming increased the percentage of embryos completing the two-cell stage to blastocyst transition in the 26-day-old group by 20%. FSH treatment of maturing oocytes from the unprimed, 26-day-old group increased the number of embryos completing the transition to the same level as those in the primed 26-day-old group, but FSH did not increase the frequency of transition in the primed 26-day-old group.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

The natural history of colorectal cancer. Opportunities for intervention.

There is now a better understanding of the natural history of colorectal cancer, which has provided a basis for intervention to influence outcome. The possible interventions include earlier detection of colorectal cancer, removal of premalignant adenomas, demonstration of the mucosal field defect that precedes neoplasia to evaluate baseline risk and its change with dietary modification, and identification of inherited and dietary risk factors. Five controlled trials evaluating early detection of colorectal cancer with fecal occult blood testing have enrolled more than 309,000 patients. Early stage cancers with improved survival has been observed, but data on mortality reduction have not as yet been reported. Studies of patients with adenomas have demonstrated high synchronous and metachronous rates as a basis for complete colon evaluation initially and a surveillance follow-up program. Hyperproliferation and lack of normal differentiation have been observed as a field defect in the colon preceding neoplasia. Inherited factors have recently been shown to be important in a larger proportion of individuals destined to develop colorectal adenomas and cancer. These observations of the natural history of colorectal cancer have provided new opportunities for the application of radiologic and endoscopic techniques in diagnosis and surveillance; each examination has its merit. Further research is needed to answer many critical questions that have been raised regarding the impact of these interventions.

Adenoma↗

Pulmonary Kaposi sarcoma in patients with AIDS: scintigraphic diagnosis with sequential thallium and gallium scanning.

Pulmonary Kaposi sarcoma associated with acquired immunodeficiency syndrome (AIDS) is difficult to diagnose because the clinical presentations and radiographic findings are nonspecific. The authors report three proved cases of AIDS-associated pulmonary Kaposi sarcoma diagnosed with sequential thallium and gallium scans. These scans demonstrated abnormal increase of pulmonary thallium uptake, whereas the gallium uptake was negative. In the authors' experience and in reports in the radiology literature, infected areas of the chest are generally thallium-negative on the delayed (3-hour) scans but are gallium-avid, whereas lymphomas are both thallium- and gallium-avid. The authors conclude that sequential thallium and gallium scans can be used to help diagnose pulmonary Kaposi sarcoma and distinguish it from other common AIDS-associated chest complications such as lymphoma and infections.

Acquired Immunodeficiency Syndrome↗

Chemotherapy screening assay using 3-dimensional cell culture.

A new alginate culture method (ACM) was used to test the effects of vincristine and 5-fluorouracil (5-FU) on the commonly used human colon carcinoma cell line HT-29. Colorimetric analysis of viability following treatment with physiologically tolerated levels of vincristine showed significant reduction of the surviving cell population. Hematoxylin and eosin staining of sections of treated organoid growths corroborated the colorimetric analyses. The ACM is inexpensive, rapid and extremely versatile. Many alginate beads containing "mini-tissue" growths of many cell lines can be used simultaneously to evaluate numerous chemotherapeutic agents in an "in vivo-like" environment.

Alginates↗

Intratubular germ cell neoplasia of the testis: identification by placental alkaline phosphatase immunostaining and argyrophilic nucleolar organizer region quantification.

We assessed the value of placental alkaline phosphatase (PLAP) immunostaining and argyrophilic nucleolar organizer region (AgNOR) quantification as techniques for the identification of intratubular germ cell neoplasia (ITGCN), and compared them with hematoxylin-eosin and periodic acid-Schiff staining. We examined 46 malignant testicular germ cell tumors for the presence of ITGCN; 43 had sufficient tubules available for assessment. We also examined 16 cryptorchid testes, 16 testicular biopsies from 10 subfertile men, and 12 normal adult intrascrotal testes. In tubules adjacent to invasive tumors, hematoxylin-eosin staining identified 30 cases (70%) of ITGCN, while PLAP and AgNOR staining identified 36 cases (84%). All the seminomas (18) and 22 of 28 nonseminomatous germ cell tumors were PLAP-positive and had high AgNOR counts. Intratubular germ cell neoplasia was not identified in the other groups examined; germ cells in these groups were PLAP-negative and had low AgNOR counts. Cells of ITGCN showed cytoplasmic block positivity with periodic acid-Schiff staining but this was not a consistent finding. We conclude that ITGCN is present adjacent to most invasive germ cell tumors, and is reliably identified by hematoxylin-eosin staining when fully developed. Periodic acid-Schiff staining was not helpful as normal spermatogonia were also positive. Staining with PLAP and AgNOR were useful diagnostic adjuncts, but results with PLAP were easier to interpret.

Alkaline Phosphatase↗

Body and breathing movements in near-term fetuses and newborn infants of type-1 diabetic women.

The generation of body and breathing movements was studied in relation to behavioural states in near-term fetuses (n = 12) and newborn infants (n = 7) of women with well-controlled type-1 diabetes. Results obtained from low-risk fetuses (n = 12) and neonates (n = 14) were used for comparison. Before birth, 2-h recordings were made of fetal heart rate and of fetal body movements, breathing and eye movements; the neonates were studied polygraphically during 6 h for heart rate, body movements, respiration, eye movements and EEG-pattern. The generation of body movements was similar in the fetuses of the diabetic and control groups. After birth, the duration per burst was longer in the diabetic group, both in state 1 and state 2, resulting in increased incidences. The incidence of fetal breathing movements tended to be higher in the diabetic group, but differences with the control group did not reach statistical significance. Breathing rate was considerably slower in fetuses of diabetic women than in control fetuses, both in C1F (P less than 0.001) and C2F (P less than 0.002). This indicates altered regulation of breathing movements in diabetic pregnancy. In the neonates, breathing rate was identical in both groups. In either group breathing was slower in state 1 than in state 2; such a difference was not present before birth. Periodic breathing occurred more often in the infants of diabetic women, especially in state 2 (P less than 0.02). Behavioural state organization was poor in the diabetic group, both before and after birth and resembled that of more immature fetuses and infants. The continuity of the poor behavioural state regulation from prenatal into postnatal life indicates that this cannot be attributed to the instantaneous unfavourable condition before birth.

Female↗

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↗

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↗

Risk and surveillance of individuals with colorectal polyps. Who Collaborating Centre for the Prevention of Colorectal Cancer.

Since colorectal adenomas are very probably the precursors of colorectal cancer, their detection and removal should result in a decrease in the incidence and mortality from colorectal cancer. Individuals who harbour an adenoma have a 30-50% probability of having additional adenomas at that time, and a 30% probability of having additional adenomas later. Adenomas are prevalent in countries where colorectal cancer is prevalent, about two-thirds of them being tubular and the rest tubulovillous or villous. The initial management of patients with an adenoma consists in searching by colonoscopy the entire colon and removing all additional polyps. Surgical resection is required wherever there is invasive cancer with adverse histological factors. Follow-up in most patients can be after 2-4 years, earlier follow-up being reserved for patients with numerous polyps or with a polyp that had been removed piecemeal. The results of ongoing trials should provide firm guidelines for follow-up and could also be used in mathematical modelling to examine alternative strategies and to help understand the evolving patterns of appearance of new polyps. Finally, a deeper understanding of the biology and inherited and acquired genetics will help identify individuals at risk for adenomas initially and at follow-up. Nutritional factors may also provide a basis for prevention of adenomas in high-risk countries. Many of these issues are being addressed in current research.

Adenoma↗

A three-dimensional system for long-term culture of human colorectal adenomas.

Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression. Progress recently was reported in the development of monolayer culture systems. The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth. We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines. Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets. The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2. Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days. Cell viability was confirmed histologically by light and electron microscopy. The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes. Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma. Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%. A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo. This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma.

Adenoma↗

The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas.

The National Polyp Study (NPS), a randomized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas, was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high-grade dysplasia in adenomas. The database included 3371 adenomas from 1867 patients. Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high-grade dysplasia (p less than 0.0001). The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas, 3.4 for villous B adenomas, and 8.1 for villous C and D adenomas relative to tubular adenomas. Increased frequency of high-grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se. The adjusted odds ratio was 1.4 (p less than 0.11) for left-sided location. Multiplicity of adenomas affected the risk for high-grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor. The adjusted odds ratio was 1.3 (p less than 0.17) for multiplicity. Increasing age was associated with risk for high-grade dysplasia in patients, and this effect was independent of the effect of adenoma size and histological type. The adjusted odds ratio was 1.8 (p less than 0.0016) for age greater than or equal to 60 yr. Gender was not associated with high-grade dysplasia. The adjusted odds ratio was 1.0 (p less than 0.95) for men. The size of the patient series, the prospective nature of the data collection, the completeness of information on all patients, the requirements of complete examination of the entire colon and pathological examination of all lesions encountered, and the exclusion of patients with previously diagnosed adenomas are, collectively, features unique to this study. The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high-grade dysplasia in colorectal adenomas.

Adenoma↗

Normal fetal hemoglobin levels in the sudden infant death syndrome.

It has been reported that infants who die of the sudden infant death syndrome (SIDS) have elevated fetal hemoglobin levels. To test this hypothesis, we determined the level of fetal hemoglobin in dead and living infants in three different laboratories by three methods: high-performance liquid chromatography, polyacrylamide-gel electrophoresis, and cell-based immunofluorescence assays for fetal hemoglobin-containing red cells (F cells). Our infant study population consisted of 67 infants who had died of SIDS, 22 control infants examined at autopsy, and 80 living infants. The fetal hemoglobin level was not higher in the infants who had died of SIDS than in the control infants for any age group analyzed. Immunofluorescence assays for F cells were also performed in blood samples from 105 mothers of infants who had died of SIDS, 55 adult female controls, 52 fathers of infants who had died of SIDS, and 67 adult male controls. The percentage of fetal hemoglobin-containing red cells in the parents of infants who had died of SIDS was not statistically different from that in sex-matched adults in the control groups. We conclude that elevated fetal hemoglobin levels in infants or their parents are not suitable for use as indicators of the risk of SIDS in the infants. Furthermore, the fetal hemoglobin level is not useful as a postmortem marker of an infant's having died of SIDS.

Adult↗

Immunohistochemical analysis of cell kinetic parameters in colonic adenocarcinomas, adenomas, and normal mucosa.

The monoclonal antibody Ki-67 identifies a nuclear antigen that is expressed in proliferating cells in G1, G2, S, and M phases of the cell cycle. An immunoperoxidase method and this antibody were used to identify proliferating cells in sections of colorectal tissues--normal colon (n = 10), colorectal polyps (n = 20), and adenocarcinoma (n = 28). Colorectal adenomas showed a uniform distribution of positive nuclear staining throughout the sections, including the cells of the adenoma surface, while staining in the normal mucosa was confined to the middle third and lower third of the crypts. Areas of polyps with numerous Ki-67-positive epithelial cells invariably showed immature or dysplastic histology and, conversely, glands that lacked such histologic features had low Ki-67 staining frequency or were negative. In adenomas, nuclei located toward the luminal surface of glands were more likely to be Ki-67-positive than those located basally in the cells. The mean Ki-67 score (a measure of positive staining nuclei) for adenomas was 45.5 compared to a mean score of 66.3 for adenocarcinomas in the carcinomas studied (P less than .001). Ki-67 score did not correlate with histologic grade or Duke's stage. Ki-67 staining can be used to characterize the proliferative characteristics of normal colonic mucosa, adenomas, and carcinomas.

Adenocarcinoma↗