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Biomedical subjects

M B Resnick

Publications and source records attributed to M B Resnick.

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

Immunohistochemical analysis of p27/kip1 expression in thyroid carcinoma.

Cyclin-dependent kinase inhibitors, including the protein product of the p27/kip1 gene, play an important role in cell-cycle regulation. Loss of p27 expression was reported in a number of neoplasms and shown to be an independent prognostic factor in colorectal, lung, and breast carcinoma By immunohistochemical analysis, we investigated p27/kip1 expression, using a polyclonal antibody, in a series of 87 benign and malignant thyroid neoplasms. We correlated its expression with the Ki-67 labeling index and other prognostic factors. All of the thyroid neoplasms examined exhibited significantly lower p27 expression than did normal thyroid tissue (P < .001). Poorly differentiated carcinomas had the lowest p27 staining frequency of all carcinomas examined. p27 staining frequency of the papillary carcinomas was significantly lower than that of the follicular carcinomas (P < .001). This difference could not be attributed solely to the inverse correlation between the staining patterns of p27 and Ki-67, which was reported for other neoplasms, because there was no significant difference between the Ki-67 labeling indices of these two groups. The follicular variant of papillary carcinoma had a significantly higher p27 staining frequency (P = .05) than did classical papillary carcinoma. We saw no significant difference in the p27 staining frequencies between minimally and widely invasive follicular carcinomas nor between localized and nonlocalized papillary carcinoma. In summary, the p27 immunostaining pattern of thyroid neoplasms is related to neoplastic transformation and varies according to tumor phenotype. It seems, however, to have limited routine diagnostic or prognostic significance in thyroid neoplasia.

Adenocarcinoma, Follicular↗
PubMed1997

MN antigen expression in normal, preneoplastic, and neoplastic esophagus: a clinicopathological study of a new cancer-associated biomarker.

Recently, a novel tumor-associated protein, termed MN, has been described in carcinomas of the uterine cervix, where its expression has been shown to be associated with malignant transformation. Because malignant transformation in the esophagus develops through a dysplasia-carcinoma sequence similar to that which occurs in the cervix, this study was performed to evaluate MN expression in normal, preneoplastic, and neoplastic tissues of the esophagus. Esophageal tumor resection specimens from 27 patients (12 squamous cell carcinomas, one multifocal squamous dysplasia, 10 Barrett's-associated adenocarcinomas, two Barrett's esophagus with dysplasia, two adenosquamous carcinomas) were immunohistochemically stained with a monoclonal antibody (clone M75) directed against the MN antigen. The localization of MN antigen, as well as the proportion of positively stained cells, were determined in sections of normal, dysplastic, and carcinomatous tissues. The staining characteristics were correlated with the pathological features of the tumors. Weak intracellular MN expression was detected only in the basal cells of normal squamous epithelium. However, inflamed and reactive squamous epithelium showed increased staining in the basal layer and in the overlying mature squamous cells. MN expression was significantly increased in dysplastic squamous epithelium (P < .001). All esophageal squamous cell carcinomas (100%) stained positively for MN antigen, where the pattern of staining was predominantly membranous. However, the degree of MN staining did not correlate with any of the pathological features of the tumors. In Barrett's epithelium, MN stained positively in all types of metaplastic cells and showed no difference in dysplastic epithelium. In contrast to squamous cell carcinomas, only 80% of esophageal adenocarcinomas were positive for MN, but the degree of MN expression was inversely correlated with histological tumor differentiation (P < .015). The results of this study suggest that (1) the tumor-associated MN antigen may play a role in proliferation and regeneration in esophageal squamous epithelium, and (2) loss of MN expression may be related to cancer progression in Barrett's-associated adenocarcinomas.

Adult↗
PubMed1996

Human eosinophils elaborate the lymphocyte chemoattractants. IL-16 (lymphocyte chemoattractant factor) and RANTES.

Eosinophils and CD4+ lymphocytes are preferentially recruited into sites of allergic inflammation. A role for eosinophils in the recruitment of CD4+ lymphocytes has not been defined. We studied the capacity of human eosinophils to release chemoattractants for T lymphocytes. Supernatants of cultured eosinophils contained chemoattractant activity for lymphocytes, which was predominantly due to IL-16 (lymphocyte chemoattractant factor) and RANTES. With neutralizing Abs, eosinophil-derived lymphocyte chemotactic activity was diminished by a mean (+/- SEM) of 60 +/- 3% with polygonal anti-IL-16 Ab, 69 +/- 4% with anti-IL-16 mAb, 48 +/- 3% with anti-CD4 F(ab) (IL-16 receptor blockade), 40 +/- 4% with anti-RANTES mAb, and 88 +/- 5% with a combination of anti-IL-16 and anti-RANTES mAbs. IL-16 and RANTES were detectable in eosinophil-derived supernatants by ELISA. Eosinophils constitutively expressed mRNA transcripts for both IL-16 and RANTES detectable by reverse transcription-PCR and contained preformed IL-16 and RANTES demonstrable by ELISA of cell lysates and by immunocytochemistry of freshly isolated eosinophils. Thus, eosinophils are a source of two cytokines, IL-16 and RANTES, that are chemoattractants for lymphocytes as well as eosinophils. These data indicate that eosinophils could contribute cytokines to enhance the recruitment of additional populations of CD4+ lymphocytes and eosinophils.

Antibodies, Monoclonal↗
PubMed1995

Growth factor expression and proliferation kinetics in periampullary neoplasms in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis develop periampullary adenomas at a high rate. However, little is known regarding the factors that control the growth, the natural history, or the malignant potential of these tumors. METHODS: In this study, the authors systematically evaluated the expression of the intestinal peptide growth factor, transforming growth factor-alpha (TGF-alpha), and its corresponding receptor, epidermal growth factor-receptor (EGF-R), in 49 periampullary adenomas and 6 periampullary carcinomas from 29 patients. Tumor proliferation rates were evaluated with the MIB-1 antibody. RESULTS: All periampullary adenomas and carcinomas (100%) had TGF-alpha expression, whereas 63% of adenomas and 67% of carcinomas expressed EGF-R. The extent of TGF-alpha expression was greater in carcinomas compared with adenomas and increased progressively in adenomas relative to the degree of dysplasia and villous architecture of these lesions. The extent of EGF-R expression correlated only with the degree of dysplasia in adenomas. With regard to proliferation kinetics, higher MIB-1 labeling indices were observed in adenomas that were larger, more severely dysplastic, and villous. Transforming growth factor-alpha, and to a lesser extent, EGF-R expression, correlated directly with the MIB-1 labeling indices. CONCLUSIONS: These results support the adenoma-carcinoma sequence in the progression of malignancy in the duodenum in familial adenomatous polyposis, suggesting a possible involvement for TGF-alpha and EGF-R expression in this process.

Adenoma↗
PubMed1995

Changes in survival patterns of very low-birth-weight infants from 1980 to 1993.

OBJECTIVE: To determine changes in survival patterns among very low-birth-weight ( < 1500 g) infants between 1980 and 1993. METHODS: The records of 12,960 infants treated in nine perinatal intensive care centers in Florida were analyzed on the basis of survival (discharged alive from hospital) according to four independent variables: birth weight, race, sex, and transport status. Survival curves were generated using log linear regression techniques for each race by sex by transport status group. RESULTS: Race, sex, and transport status correlated significantly with survival: survival percentages were higher among black infants, female infants, and infants transported to the perinatal intensive care centers than among white infants, male infants, and those admitted initially to the tertiary care centers. After 1985, 95% of neonates with birth weights between 1200 and 1500 g survived. In addition, survival of 500- to 500-g transported black male infants increased from zero to near 80% during the 13-year period; that of 500- to 550-g inborn white female infants rose from 35% to 70%. CONCLUSIONS: These results illustrate the value of taking into account race, sex, and transport status in efforts to understand the contribution that neonatal intensive care of extremely low-birth-weight infants makes to the lowering of infant mortality, and of using multivariable statistical procedures to generate predicted survival probabilities for different subpopulations. These probabilities can be applied to (1) predicting survival for specific subgroups of extremely low-birth-weight infants, and (2) helping physicians develop clinical guidelines for extending care to infants at the threshold of viability.

Birth Weight↗
PubMed1995

Human eosinophils migrate across an intestinal epithelium in response to platelet-activating factor.

BACKGROUND/AIMS: Transmigration of eosinophils across intestinal epithelia occurs in a variety of mucosal inflammatory disorders and results in the formation of crypt abscesses containing eosinophils. However, the conditions required to drive transepithelial migration of eosinophils are not understood. METHODS: This study investigated eosinophil migration across intestinal epithelia using purified eosinophils and confluent monolayers of the human intestinal epithelial cell line T84. RESULTS: Unactivated eosinophils (i.e., no granulocyte/macrophage colony-stimulating factor [GM-CSF] preexposure) did not migrate across T84 monolayers in the presence of transepithelial gradients of C5a, n-formyl-methionyl-leucyl-phenylalanine (fMLP), or platelet-activating factor (PAF). In contrast, activation of eosinophils by coincubation or pretreatment with GM-CSF enabled transepithelial migration in response to PAF but not to C5a or fMLP gradients in a time- and dose-dependent fashion. Specificity was confirmed by both the PAF receptor antagonist WEB-2086 and the PAF enantiomer 2-lyso-beta-acetyl-gamma-O-hexadecyl. Finally, addition of functionally inhibitory monoclonal antibodies to CD11b but not CD11a, very late activation antigen (VLA-4), or intracellular adhesion molecule 1 inhibited eosinophil migration. CONCLUSIONS: These studies establish that physiologically directed migration of eosinophils across model epithelia occurs but that this process is governed by the state of eosinophil activation, the specific chemotactic gradient imposed, and the availability of specific surface integrins to participate in putative eosinophil-epithelial adhesion steps.

Adult↗
PubMed1995

An index for early assessment of neonatal survival in low birthweight infants.

Since its development in the 1950s, the Apgar index has come into widespread use as a tool to evaluate neonatal condition, with predictive implications for mortality and morbidity. However, Apgar scores were validated in predominantly term infants and have questionable prognostic value for low birthweight infants. The purpose of this study was to develop a survival index applicable to premature infants. Thirty-six perinatal variables were evaluated initially, based on data from 441 neonates weighing 500 to 1800 g. A multifactorial index of nine variables was derived, each independently related to mortality. Sensitivity of the index was 95%, specificity was 68%, positive predictive value was 90%, and negative predictive value was 81%. This index provides the most accurate tool yet reported in the literature for predicting concurrent survival of premature infants. The tool is recommended for use as an index of neonatal condition for low birthweight infants. Its additional use, as a predictor of the likelihood of survival would require time and place specific validation.

Apgar Score↗
PubMed1995

Hepatic adenoma in the pediatric age group. Clinicopathological observations and assessment of cell proliferative activity.

The clinicopathological findings of eight children with hepatic adenoma in the absence of cirrhosis are presented. The lesions ranged in diameter from 0.1 to 14.5 cm. Associated disorders were Fanconi's anemia, type I glycogen storage disease. Hurler's disease, and severe combined immunodeficiency with ADA deficiency. The remaining three children had adenoma without known associated disorders. In the children with glycogenosis and Hurler's disease the adenomas were multiple. Significant dysplasia occurred in the two children with Fanconi's anemia; however, the lesions behaved in a benign fashion--one with regression of the tumor after cessation of androgen therapy and the other with nonrecurrence after complete resection. Proliferating cell nuclear antigen (PCNA) labeling index (LI) of the adenoma arising in patients with Fanconi's anemia was significantly greater than the PCNA-LI of adenoma in the other children (mean 4.1% versus 0.9% of nuclei), approaching the lower end of the spectrum for reported hepatocellular carcinoma cases. We emphasize that the worrisome pathology that may occur in hepatic adenoma in children, particularly with Fanconi's anemia, does not necessarily predict malignant behavior. The association of hepatic adenoma with Hurler's disease or severe combined immunodeficiency has not been reported previously.

Adenoma, Liver Cell↗
PubMed1994

IL-4 directly modulates function of a model human intestinal epithelium.

Intestinal epithelia are in intimate contact with subepithelial and intraepithelial lymphocytes. When stimulated, mucosal lymphocytes generate inflammatory cytokines such as IL-4 and IFN-gamma. We have shown that IFN-gamma directly regulates epithelial function. It is unknown whether IL-4 might influence epithelial function and, if so, whether such influences are similar to or differ from those exerted by IFN-gamma. In this study, we examine the effect of human IL-4 on barrier function, ion transport, and immune accessory ligand expression on T84 cells, a crypt-like epithelial cell line. Basolateral exposure of epithelial monolayers to IL-4 attenuated epithelial barrier function by greater than 65% in a dose (50% of effective dose = 1 U/ml)- and time (t1/2 = 24 h)-dependent fashion, and was inhibitable by neutralizing anti-IL-4 and anti-IL-4R Ab. Stimulated Cl- secretion, as measured by epithelial short circuit current, was diminished by as much as 70% by IL-4. Epithelial preexposure to IL-4 brought about a greater than twofold increase in beta 2 integrin-dependent neutrophil adhesion to epithelial, but retarded neutrophil migration into and across epithelial monolayers. ELISAs revealed that epithelial exposure to IL-4 had no effect on cell surface expression of MHC class I, MHC class II, or ICAM-1. These results indicate that IL-4, like IFN-gamma, may serve to regulate intestinal epithelial function, but that resulting phenotypes may be cytokine specific. We speculate from these data that activation of the basolateral receptor for IL-4 potentially provides a new strategy for damping the cellular component of active inflammation in the intestine.

Cell Adhesion Molecules↗
PubMed1993

Activated eosinophils evoke chloride secretion in model intestinal epithelia primarily via regulated release of 5'-AMP.

Eosinophils may be prominent in intestinal diseases including allergic gastroenteritis, inflammatory bowel disease, enteritis associated with hypereosinophilic syndromes (HES), and parasitic diseases. Unlike normal blood eosinophils, those that circulate in HES and those that infiltrate inflamed tissue exhibit an "activated" phenotype. To model intestinal epithelial-eosinophil interactions, we used peripheral blood eosinophils and human crypt-like T84 epithelial cell-line monolayers. Eosinophils from normal, mildly atopic donors, only if activated by PMA or primed with granulocyte-macrophage-CSF for 48 h, as well as eosinophils from HES patients elicited a short circuit current when applied apically to T84 monolayers. This eosinophil-derived bioactivity, which was transferable in cell-free supernatants and in < 1000 m.w. ultrafiltrates, stimulated electrogenic Cl- secretion, as indicated by inhibition with basolateral bumetanide or gluconate substitution and by enhancement of the rate constant for 125I efflux from preloaded T84 cells. This secretagogue activity was blocked in both intact activated eosinophils and in eosinophil-conditioned supernatants, by 8-phenyl-theophylline, indicating involvement of an adenosine receptor. Ion exchange and reversed-phase HPLC analyses demonstrated that eosinophil supernatant ultrafiltrates contained elevated levels of 5'-AMP that was converted to adenosine after incubation with epithelium. Inhibition of epithelial apical membrane ecto-5'-nucleotidase ablated the conversion to adenosine. These studies establish that activated eosinophils elicit Cl- secretion from intestinal epithelial and that 5'-AMP released by eosinophils followed by its conversion to adenosine at the epithelial surface is the basis for this response.

Adenosine Diphosphate↗
PubMed1993

Mechanisms of eosinophil recruitment.

As with other types of leukocytes, mechanisms that function to enable the recruitment of eosinophils into specific sites of immune reactions involve a complex and cumulative interplay of many molecules and pathways. No single chemoattractant is specific for eosinophils, but rather various chemoattractants active on eosinophils can also elicit migration of other specific cell types. Humoral mediators causing eosinophil migration include C5a and platelet-activating factor, whereas cytokines active as eosinophil chemoattractants include interleukin (IL)-2, IL-3, IL-5, granulocyte/macrophage colony-stimulating factor, lymphocyte chemoattractant factor, and RANTES. Eosinophils utilize several pathways to adhere to vascular endothelial cells, including binding to intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). The lack of binding of neutrophils to VCAM-1 and the enhanced expression of VCAM-1 elicited by IL-4 contribute to preferential eosinophil accumulation. Eosinophil recruitment is dependent not only on ligands expressed on eosinophils and molecules inducible on endothelial cells but also on processes active during transendothelial migration and extravascular migration in the extracellular spaces.

Animals↗
PubMed1993

Human eosinophils can express the cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha.

By in situ hybridization, 44-100% of the blood eosinophils from five patients with hypereosinophilia and four normal subjects exhibited intense hybridization signals for TNF-alpha mRNA. TNF-alpha protein was detectable by immunohistochemistry in blood eosinophils of hypereosinophilic subjects, and purified blood eosinophils from three atopic donors exhibited cycloheximide-inhibitable spontaneous release of TNF-alpha in vitro. Many blood eosinophils (39-91%) from hypereosinophilic donors exhibited intense labeling for macrophage inflammatory protein-1 alpha (MIP-1 alpha) mRNA, whereas eosinophils of normal donors demonstrated only weak or undetectable hybridization signals for MIP-1 alpha mRNA. Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1 alpha mRNA. By Northern blot analysis, highly enriched blood eosinophils from a patient with the idiopathic hypereosinophilic syndrome exhibited differential expression of TNF-alpha and MIP-1 alpha mRNA. These findings indicate that human eosinophils represent a potential source of TNF-alpha and MIP-1 alpha, that levels of expression of mRNA for both cytokines are high in the blood eosinophils of hypereosinophilic donors and in eosinophils infiltrating nasal polyps, that the eosinophils of normal subjects express higher levels of TNF-alpha than MIP-1 alpha mRNA, and that eosinophils purified from the blood of atopic donors can release TNF-alpha in vitro.

Cells, Cultured↗
PubMed1992

A random coefficient growth curve analysis of mental development in low-birth-weight infants.

In many medical studies, longitudinal data are collected on each of a sample of patients. The objectives of such studies often are: to estimate and test bivariate or multivariate relationships within each of several groups of patients from these repeated measures data; to compare these relationships among groups; and to test for the effects of baseline covariates on the relationships. This paper illustrates the use of statistical methods for growth curve analysis recently proposed by Vonesh and Carter for achieving these goals by relating a measure of preschool cognitive development to age in four race by sex groups of low-birth-weight infants. Significant declines in Bayley's Mental Development Index (MDI) with increasing age were found in all groups. Birth-weight did not significantly influence the rate of decline but did influence the overall level of performance. Even so, in the group most comparable to Bayley's normative population, predicted MDI was near the norm even for extremely low-birth-weight infants (that is, 1000 grams). Although there is some risk of mental deficit associated with prematurity, eventual developmental delays in low-birth-weight infants frequently are acquired with age. The rate of decline in MDI was significantly associated with race and mother's education. Assumptions required for the valid application of these methods are discussed and tested in the setting of this applied problem. The assumptions appeared valid in this application. We conclude with a brief discussion of available alternatives when the assumptions are violated and point to areas for future research.

Age Factors↗
PubMed1992

Educational outcome of neonatal intensive care graduates.

Studies of developmental outcome of neonatal intensive care unit graduates have generally been limited to the first 2 to 3 years of life, with outcome determined by psychometric tests. This study followed neonatal intensive care unit graduates born 1975 through 1983 (n = 457) into the public school system and compared their educational outcomes with those of newborn nursery graduates (n = 656). Outcomes were evaluated by placement in four academic categories: regular classroom, academic problems, speech/language impairment, and major impairment. Educational outcomes for children of both groups were essentially the same. Their placement in the four academic categories were equally affected by nonmedical variables, primarily income (below/above poverty level), race, and sex. Seventy percent of poverty-level children were in one of the three problem categories, compared with 40% of children above poverty level. Neither neonatal intensive care unit treatment nor low birth weight were major predictors of educational outcome. The only clear-cut neonatal intensive care unit effect occurred among children born with sensory or physical impairments. Therefore, in order to reduce poor educational outcomes, follow-up and intervention programs should be targeted primarily to children with diagnosable handicaps and from minority, low-income families.

Child↗
PubMed1990

Effects of birth weight and sociodemographic variables on mental development of neonatal intensive care unit survivors.

Neonatal intensive care unit survivors (N = 494) from 10 tertiary care centers were evaluated over the first 4 to 5 years of life to determine the relative contributions of birth weight and sociodemographic factors to mental development. Six sociodemographic factors were studied: sex, race, family income, and mother's marital status, age, and educational level; the last five factors also are known to be associated with premature birth. Mental development was measured with the Bayley Scales of Infant Development (12 to 24 months) and the Stanford Binet Intelligence Test (4 to 5 years). Each factor's influence was assessed by multivariate analysis. Birth weight had limited long-term implications; at 4 to 5 years, only infants with birth weights less than 1000 gm had significantly lower scores than those in other birth weight categories. Sociodemographic variables had a greater impact on mental development, with age-dependent differences found between nonwhite and white children and between children with mothers of low, medium, and high educational levels.

Adult↗
PubMed1989

Effect of birth weight, race, and sex on survival of low-birth-weight infants in neonatal intensive care.

Survival for low-birth-weight infants has traditionally been analyzed by birth weight categories spanning considerable ranges of weight. We developed a finer description of survival rates to allow estimation of survival percentages for infants of any specific birth weight between 500 and 2500 gm. Our sample consisted of 16,183 infants treated in tertiary neonatal intensive care between 1980 and 1987. Their survival data were analyzed by 50 gm increments between 500 and 2500 gm, and a continuous survival curve was constructed by log linear regression methods. Mortality differences between males and females and blacks and whites were analyzed. Survival for females was higher than males between 500 and 1500 gm and higher for blacks than whites between 650 and 1500 gm. Between 1500 and 2500 gm, no significant effects of birth weight, race, or sex were observed, with survival remaining stable at approximately 95% across all combinations of variables.

Birth Weight↗
PubMed1989

Predictive value of Apgar scores for developmental outcome in premature infants.

For more than two decades, Apgar scores have been used to predict developmental outcome in newborns. However, most studies have used full-term babies for their data base, and the predictive value of Apgar scores for low birthweight infants has remained unclear. This study was designed to provide a data base for premature infants, demonstrating to what degree Apgar scores predict developmental outcome. We tested Apgar scores alone and in combination with two other easily quantified variables, birthweight and gestational age, as predictors of risk for 256 infants weighing less than 1800 gm at birth. Although significant correlations existed between Apgar scores and Bayley Mental and Psychomotor Developmental Indices, multiple regression analyses demonstrated that these relationships were not significant independent of birthweight and gestational age. That is, after controlling for birthweight and gestational age, Apgar scores did not predict morbidity in low birthweight infants and should not be used to provide a developmental prognosis.

Apgar Score↗