A cryptic balanced translocation (5;17), a puzzle revealed through a critical evaluation of the pedigree and a FISH focused on candidate loci suggested by the phenotype.

We report a case of a woman with a cryptic balanced translocation between chromosomes 5 and 17, suspected during genetic counseling. The woman had a history of previous fetal losses attributed to lissencephaly and intra uterine growth retardation (IUGR) and a daughter with dysmorphic features and mental retardation, previously attributed to a small deletion 5pter, detected years ago by a first generation CGH-array. This peculiar combination of personal and family history suggested the opportunity to carry out a FISH approach, focusing on chromosomes 5 and 17, based on the idea that a malsegregation secondary to a balanced translocation, might have escaped the first CGH array. This approach allowed the identification of a balanced translocation in the mother, FISH in the affected child confirmed the partial 5p deletion predicted by the previous CGH array and identified a new 17p duplication that had not been detected before. The described translocation opens the possibility of alternative imbalances that were probably responsible for previous fetal losses. The imbalances were confirmed by a new high resolution SNP array. We conclude that despite the availability of highly effective and sensitive genomic approaches a careful evaluation of medical history is highly recommended since it can suggest clinical hypothesis that can be confirmed by more classical and molecular cytogenetic based approaches.

Factors influencing law enforcement decisions to adopt an evidence-based robbery prevention program.

Homicide is the leading cause of workplace death among small retail and service businesses in the United States. Evidence-based programs have been shown to reduce robbery and robbery-related crimes in small retail businesses; however, reaching small businesses with programs has been difficult. As small businesses typically have no corporate backing or trade affiliation, police departments have been identified as potential vehicles for program dissemination. A national sample of 300 law enforcement agencies was surveyed to identify facilitators and barriers to adoption and sustainability of an evidence-based program. The questionnaire was developed using behavioral theory concepts and administered via telephone. Preliminary findings suggest the primary facilitators to program adoption included organizational capacity factors such as staff buy-in, dedicated personnel and financial support. Competing responsibilities was the primary barrier identified by agencies. Agency size and program complexity were identified as potential predictors of program adoption. Identifying agency and program-specific characteristics that influence program adoption by law enforcement agencies will be valuable for marketing programs to agencies that have the infrastructure to support and sustain program dissemination. Understanding these factors will optimize the reach of evidence-based strategies to small businesses.

Iodine deficiency in Calabria: characterization of endemic goiter and analysis of different indicators of iodine status region-wide.

The distribution of goiter prevalence in schoolchildren (no.=13,984, age 6-14 yr), the neonatal TSH results obtained from the congenital hypothyroidism screening program and the urinary iodine excretion values (no.=284) were employed for the assessment of iodine deficiency in Calabria, a Southern Italy region. Data were collected during the years 1990-1996. In the inland territory, goiter prevalence ranged from 19 to 64%. At sea level, there was a great variability of goiter prevalence, with values varying from 5.3 to 25.7%. The analysis of the neonatal hypothyroidism screening program data (no.=21,078) showed a 14.8% frequency of TSH levels >5 microU/ml whole blood in newborns from the inland territory and a 14.1% frequency at sea level. Urinary iodine excretion resulted (mean+/-SD) 53.8+/-43.4 microg/l (range: <20 to 189 microg/l) in the inland territory and 89.6+/-59.8 microg/l (range: 26 to 333 microg/l) at sea level. Median urinary iodine excretion values in 13 villages or small towns of the inland territory ranged from 31 to 57 microg/l. In 2 major towns located at sea level, the median iodine excretion values were 72 microg/l in Crotone main city and 94 microg/l in Reggio Calabria main city. The data indicated that moderate, with pockets of severe iodine deficiency is present in the inland region while iodine supply varies from sufficient to marginally low in the coastal areas. Mild iodine deficiency was found in a major town located at sea level.

Sodium iodide symporter and pendrin expression in human thyroid tissues.

Thyroid cells synthesize thyroid hormones through a multistep process during which iodide is transported through the basolateral and the apical membranes of thyrocytes. Two genes that participate in these transports and the corresponding proteins, namely sodium iodide symporter (NIS) and pendrin, the product of the Pendred syndrome gene, have recently been characterized. We studied NIS and pendrin expression at the mRNA and protein levels by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method and by single and double immunostaining in normal and pathological human thyroid tissues. In normal tissue, NIS and pendrin were detected in about 20% and 40%-60% of thyrocytes, respectively. The number of NIS- and pendrin-positive cells was much higher in hyperfunctioning tissue from Graves' disease or toxic adenoma. In hypofunctioning adenomas and carcinomas, the number of NIS- and pendrin-positive cells was low or nonexistent. Three types of follicular cells were observed in positive tissues: NIS-negative/pendrin-negative cells, NIS-positive/pendrin-positive cells, and NIS-negative/pendrin-positive cells. The first two types of cells appear to be resting and active cells, respectively, but the functional status of NIS-negative/pendrin-positive thyrocytes remains to be determined.

Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX, LNOX, Duox) genes and proteins in human thyroid tissues.

The large homolog of NADPH oxidase flavoprotein LNOX2, and probably LNOX1, are flavoproteins involved in the thyroid H(2)O(2) generator. Western blot analysis of membrane proteins from normal human thyroid, using antipeptide antibodies, indicated that LNOX1,2 are 164-kDa glycoproteins and that N-glycosylated motifs account for at least 10-20 kDa of their total apparent molecular mass. Northern blot analysis of 23 different human tissues demonstrated that LNOX2 messenger RNA (mRNA) is strongly expressed only in the thyroid gland, although blast analysis of expressed sequence tags databases indicated that LNOX genes are also expressed in some nonthyroid cells. We investigated LNOX1,2 gene and protein expressions in normal and pathological human thyroid tissues using real-time kinetic quantitative PCR and antipeptide antibodies, respectively. In normal tissue, LNOX1,2 are localized at the apical pole of thyrocytes. Immunostaining for LNOX1,2 was heterogeneous, inside a given follicle, with 40-60% of positive follicular cells. Among normal and pathological tissues, variations of LNOX1 and LNOX2 mRNA levels were parallel, suggesting a similar regulation of both gene expressions. Whereas LNOX mRNAs seemed slightly affected in benign disease, the expression of protein was highly variable. In multinodular goiters, 40-60% of cells were stained. In hypofunctioning adenomas, LNOX immunostaining was highly variable among follicles, whereas sodium/iodide (Na+/I-) symporter immunostaining was decreased. In hyperfunctioning thyroid tissues, only few cells (0-10%) were weakly stained, whereas sodium/iodide symporter staining was found in the majority of follicular cells. In conclusion, LNOX proteins are new apical glycoproteins with a regulation of expression that differs from other thyroid markers.

Chromogranin A and the alpha-subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma.

Using specific immunoradiometric assays, we evaluated the clinical usefulness of chromogranin A and the alpha-subunit of glycoprotein hormones in neuroendocrine tumours of neuroectodermic origin. The serum alpha-subunit of glycoprotein hormones was only slightly increased in 2 out of 44 medullary thyroid carcinoma or phaeochromocytoma patients with increased calcitonin or 24-hour urinary metanephrine levels. Serum chromogranin A was increased in 12 of 45 (27%) medullary thyroid carcinoma patients with an elevated calcitonin level and in 4 of 16 medullary thyroid carcinoma patients (25%) with an undetectable calcitonin level, in 5 of 7 phaeochromocytoma patients with increased urinary catecholamine and metabolite excretion, and in 2 of 3 patients with a non-functioning phaeochromocytoma. During follow-up, the course of chromogranin A was found to parallel that of tumour burden and/or 24-hour urinary metanephrine in 5 phaeochromocytoma patients. We conclude that chromogranin A measurement is not recommended for the diagnosis of medullary thyroid carcinoma patients. It may be useful in patients with functioning and non-functioning phaeochromocytomas as a follow-up marker. In neuroendocrine tumour patients with elevated calcitonin secretion, the serum alpha-subunit of glycoprotein hormone measurement may help differentiate medullary thyroid carcinoma or phaeochromocytoma patients from other endodermal-derived neuroendocrine tumour patients in whom it is frequently elevated.

Expression of nicotinamide adenine dinucleotide phosphate oxidase flavoprotein DUOX genes and proteins in human papillary and follicular thyroid carcinomas.

Duox2, and probably Duox1 are glycoflavoproteins involved in the thyroid H2O2 generator functionally associated to thyroperoxidase (TPO). We investigated both DUOX1 and DUOX2 gene expressions using quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 47 thyroid carcinomas, including 10 paired normal/tumoral tissues. In carcinomas, variations of DUOX1 and DUOX2 mRNA levels were parallel, indicating that control mechanisms of both gene expressions operate in tumors as well as in normal thyroid tissues; DUOX1 expression was in the normal range in 20, was decreased up to 50-fold in 8, and increased up to 7-fold in 19 samples. DUOX2 expression was in the normal range in 15, was decreased up to 200-fold in 10, and increased up to 5-fold in 22 samples. In the 10 paired samples, variations of DUOX and TPO gene expressions were not correlated. We analyzed Duoxl/2 protein expression in 86 tumor samples using an antipeptide antiserum reacting with both Duox proteins. In normal tissue, Duox proteins are localized at the apical pole of thyrocytes, with 40% to 60% of thyrocytes being stained. In the 86 cancer tissues, immunostaining was absent in 19 samples, was low in 32, and normal or even slightly increased in the other 35 samples. The expression of Duox proteins was related to tumor differentiation, being more frequently found in neoplastic tissues that were able to pick up radioiodine, and in those with a detectable expression of sodium iodide symporter (NIS), pendrin and TPO.

Treatment of advanced medullary thyroid cancer with an alternating combination of doxorubicin-streptozocin and 5 FU-dacarbazine. Groupe d'Etude des Tumeurs à Calcitonine (GETC).

Combinations of doxorubicin and streptozocin and 5-FU and dacarbazine were given alternately to 20 patients with metastatic medullary thyroid carcinoma. Three partial responses and 10 long-term stabilizations were observed. No unexpected toxicity occurred.

Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients.

To determine the clinical impact of endogenous subclinical hyperthyroidism, specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients (3 males and 20 females; mean age, 43 +/- 9 yr) and 23 age-, sex-, and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey questionnaires. Because the heart is one of the main target organs of the thyroid hormone, cardiac morphology and function were also investigated by means of standard 12-lead electrocardiogram (ECG), 24-h Holter ECG, and complete Doppler echocardiography. Stable endogenous subclinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study (TSH, 0.15 +/- 0.1 mU/L; free T(3), 6.9 +/- 1.1, pmol/L; free T(4), 17.2 +/- 2.3, pmol/L). Fifteen patients were affected by multinodular goiter, and eight patients by autonomously functioning thyroid nodule. The mean Symptoms Rating Scale score (9. 8 +/- 5.5 vs. 4.3 +/- 2.2, P: < 0.001) and both the mental (36.1 +/- 9.5 vs. 50.0 +/- 8.5, P: < 0.001) and physical (42.6 +/- 8.0 vs. 55. 6 +/- 4.1, P: < 0.001) component scores of Short Form 36 Health Survey documented a significant prevalence of specific symptoms and signs of thyroid hormone excess and notable impairment of quality of life in patients. Holter ECG showed a higher prevalence of atrial premature beats in endogenous subclinical hyperthyroid patients than in the controls, but the difference was not statistically significant, although the average heart rate was significantly increased in the patients (P: < 0.001). An increase of left ventricular mass (162 +/- 24 vs. 132 +/- 22 g, P: < 0.001) due to the increase of septal (P: = 0.025) and posterior wall (P: = 0.004) thickness was observed in patients. Systolic function was enhanced in patients as shown by the significant increase of both fractional shortening (P: = 0.005) and mean velocity of heart rate-adjusted circumferential fiber shortening (P: = 0.036). The Doppler parameters of diastolic function were significantly impaired in the patients as documented by the reduced early to late ratio of the transmitral flow velocities (P: < 0.001) and the prolonged isovolumic relaxation time (P: = 0.006). These data indicate that endogenous subclinical hyperthyroidism has a relevant clinical impact and that it affects cardiac morphology and function. Moreover, they suggest that treatment of persistent endogenous subclinical hyperthyroidism should be considered also in young and middle-aged patients to attenuate specific symptoms and signs of thyroid hormone excess, ameliorate the quality of life, and avoid the consequences to the heart of long exposure to a mild excess of thyroid hormone.

The statistical analysis of neonatal TSH results from congenital hypothyroidism screening programs provides a useful tool for the characterization of moderate iodine deficiency regions.

TSH data from the congenital hypothyroidism screening program were analyzed in a mild to moderate iodine deficiency region. Neonatal TSH levels were measured at day 4-5 of life in 22,384 infants (99% coverage; 51.1% males, 48.9% females). The cut off TSH value for recall was established at 20 microUl/ml whole blood. TSH values > 20 microUl/ml were excluded from further analysis of the data. The frequency distribution analysis showed that the median neonatal TSH level was 2 microUl/ml and the mode (28% of newborns) corresponded to neonatal TSH values < 1 microUl/ml. TSH levels above 5 microUl/ml were observed in 14.4% children and the 97% cut off was 11 microUl/ml. When examined in relation to the areas of newborn origin, the individual 97% cut off values varied from 8 to 14 microUl/ml. Accordingly, the frequency of TSH levels above the 97% cut off value calculated for the entire newborn series (> 11 microUl/ml) ranged from 2.1% to 4.6%. A significant correlation was found between the frequency of neonatal TSH levels > 11 microUl/ml and both goiter prevalence (r2 = 0.88; p = 0.0019) and median urinary iodine excretion (r2 = 0.86; p = 0.0077) observed in those areas for which epidemiological data were available (n = 7). The results indicate that neonatal TSH data from the congenital hypothyroidism screening programs can be used for monitoring mild to moderate iodine deficiency regions.

Pediatric mortality probability estimated from pre-ICU severity of illness.

OBJECTIVE: The Pediatric Risk of Mortality (PRISM) score is a measure of illness severity based on abnormalities observed in the bedside examination and laboratory assessment. PRISM scores obtained after pediatric intensive care unit (PICU) admission predict mortality probability, but no previous efforts to evaluate mortality risk before PICU admission have been reported. Our study was performed on patients admitted to PICUs at four pediatric tertiary care centers to derive a quantitative estimate of hospital mortality probability as a function of PRISM scores obtained at referring hospitals before PICU transfer. Performance of the model was tested by evaluating accuracy of mortality predictions obtained from pre-ICU PRISM scores in a separate validation set of patients. METHODS: Patients were randomized to the derivation or validation sets. Data were recorded prospectively from observations made at hospitals referring to the study PICUs. Patients included 780 infants and children with medical and surgical emergencies and trauma. Electively admitted patients were excluded from analysis. RESULTS: The relationship between mortality probability (P) and the pre-ICU PRISM score is expressed by the equation: P = er/(1 + er). In this equation, r is an empirical function of the pre-ICU PRISM score: r = .197 x PRISM - 4.705. The mortality probability rises from near 0 at low scores, approaching 1 (certainty) above a PRISM score of 40. Mortality probability exceeds 10% at a score of 13 and exceeds 50% at a score of 24. Performance of predictions in the validation set of patients was evaluated for five categories of mortality probability. The observed number of deaths corresponded to predicted mortality across the range of illness severity. When compared for each tertiary institution, observed mortality rates were similar to predictions for three of four institutions. For data obtained at institution D, the observed mortality of 17% significantly exceeded the 7% predicted rate. In infants younger than 1 year, as well as children 1 year and older, observed mortality rates were similar to predicted. CONCLUSIONS: The pre-ICU PRISM score as a measure of illness severity provides an estimate of hospital mortality probability. Further investigation is required to determine the use of pre-ICU mortality estimates in making clinical decisions.

Localization of seminal plasma transforming growth factor-beta1 on human spermatozoa: an immunocytochemical study.

OBJECTIVE: To localize immunocytochemically transforming growth factor beta1 (TGF-beta1) in human spermatozoa. DESIGN: Incubation of spermatozoa with anti-TGF-beta1 antiserum at various pH. SETTING: Human volunteers in an academic research institute. PATIENTS: Young healthy fertile men. INTERVENTIONS: Semen specimens were collected. RESULTS: At neutral pH and at physiological pH of seminal plasma, TGF-beta1 immunostaining was detected predominantly at the postacrosomal region of the head, at the neck, and at the middle piece of the tail. Transforming growth factor-beta1 also was found occasionally at the axial filament complex of the connecting piece and the ring. The acrosomal cap section of the head, the principal piece, or the end piece of the tail were immunocytochemically negative for TGF-beta1. The TGF-beta1 immunostaining pattern at acidic pH was similar to that at neutral pH and at physiological pH of seminal plasma, but a greater intensity of immunostaining was found at acidic pH than that at neutral pH. CONCLUSION: These results suggest that an in vivo activation of seminal plasma latent TGF-beta1 may take place in the acidic environment of vagina, which results in a greater amount of activated TGF-beta1 and, in turn, with an enhanced "coating" of TGF-beta1 to spermatozoa.

Characterization of latent transforming growth factor-beta from human seminal plasma.

PROBLEM: Human seminal plasma is known to exhibit immunosuppressive activity. Transforming growth factor beta (TGF-beta) has been identified as an immunosuppressive factor in human seminal plasma. Biologically active TGF-beta represents a family of 25-kDa homodimeric proteins linked with disulfide bonds. TGF-beta associates with high molecular weight proteins noncovalently to form a type of latency that is biologically inactive. Quantitative distribution of active form of TGF-beta versus inactive latent form of of TGF-beta, and mechanism of the TGF-beta activation in human seminal plasma remain to be elucidated. PURPOSE: To characterize seminal plasma latent form of TGF-beta, including its concentration, and the mechanism underlying the activation of TGF-beta. METHOD: Gel filtrations on ACA-34 and Biogel P-60 were used to fractionate seminal plasma. TGF-beta was measured by enzyme immunoassay using antibodies specific for TGF-beta 1 and TGF-beta 2, respectively. Radioreceptor assay with recombinant human [125I]-TGF-beta 1 was applied to qualitatively identify TGF-beta 1. Kinetic experiments with various pH, temperature and time, along with protease inhibitors, were performed to delineate the activation mechanism of latent TGF-beta 1. RESULTS: Human seminal plasma contained both TGF-beta 1 and TGF-beta 2, predominantly in latent form. The total concentration of TGF-beta 1 averaged 238 ng/ml versus an average of 18 ng/ml for TGF-beta 2. The in vitro activation or release of TGF-beta 1 from latent TGF-beta 1 was achieved only at acidic pH of < 4.0, and was time and temperature dependent. At pH 3.7 and 37 degrees C, a significant activation of latent TGF-beta 1 was achieved after an incubation of only 15 min, reached the maximum at 120 min, and the activated TGF-beta 1 remained relatively stable for at least 24 h. The activation was not inhibitable by a series of protease inhibitors examined, alone or in combination (e.g., phenyl-methylsulfonyl fluoride, E-64, pepstatin, leupeptin, ethylenediamine tetraacetic acid). Competitive radioreceptor assay established the functional identity of TGF-beta 1 in human seminal plasma with recombinant human TGF-beta 1. CONCLUSION: Human seminal plasma TGF-beta is biologically activated from high molecular weight latent TGF-beta by acid pH. The acidic environment of female lower genital tract could represent an in vivo physiological condition for activation of seminal plasma TGF-beta that may immunologically protect the integrity of sperm.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p < 0.01), between length of infusion of fentanyl and NAST score (r = .70, p < 0.05), and between chloral hydrate dosage and NAST score (r = .62, p < 0.05). These findings suggest the need for an observation protocol and a possible weaning regimen after fentanyl is discontinued.

Transforming growth factor beta as an immunosuppressive protein in human seminal plasma.

PROBLEM: Human seminal plasma is known to exhibit immunosuppressive activity in seminal plasma. PURPOSE: The purpose was to characterize immunosuppressive proteins in seminal plasma. METHOD: Gel filtration fractions of 100 to > 440 kDa were identified that inhibited DNA synthesis and killing activity of interleukin-2 stimulated lymphocytes. RESULTS: The fractions exhibiting immunosuppression also inhibited DNA synthesis in a mink lung cell bioassay commonly used to measure the activity for transforming growth factor beta (TGF-beta). The negative growth activity was diminished by a TGF-beta neutralizing monoclonal antibody. TGF-beta was further detected in the active fractions by Western immunoblot. CONCLUSIONS: These results identified TGF-beta as an immunosuppressive protein in human seminal plasma and may provide insight into the role of immunosuppression played by seminal plasma, such as in reproduction and neoplasia.

Determination of salivary digoxin with a dry strip immunometric assay.

Analysis of salivary digoxin using a rapid dry chemistry, enzyme-labeled immunometric assay (ELIA) was compared with fluorescence polarization immunoassay (FPIA). Saliva and serum samples were obtained from 40 hospitalized patients who were taking digoxin chronically and from 8 patients just prior to treatment with digoxin. Unstimulated saliva samples were collected from 20 patients; however, saliva volumes from 10 pediatric patients were inadequate to permit analysis by FPIA, and 1 other had unmeasurable concentrations by both methods. Stimulated saliva was collected by having patients chew a small piece of Parafilm for 1-2 min. Salivary digoxin was analyzed using the same procedure recommended for serum digoxin by each manufacturer. There were no significant differences found between ELIA and FPIA determinations of unstimulated or stimulated salivary digoxin, serum digoxin, or saliva/serum concentration ratios. The saliva/serum ratio of the unstimulated group was approximately twice that of the stimulated group (p less than 0.01) by both methods, suggesting that salivary digoxin concentration decreases with increased saliva production rate. Excellent correlations were found between ELIA and FPIA salivary digoxin concentrations and between stimulated saliva and serum concentrations by both assays. Weaker correlations were observed between unstimulated saliva and serum concentrations. There was no evidence of assay interference with either method in eight nondigitalized patients, each taking an average of 6.5 medications. The ELIA appears to provide equivalent results compared with the FPIA for the determination of salivary digoxin concentration. Further investigations are needed before salivary digoxin concentration monitoring can be recommended as an acceptable alternative to serum monitoring.

Murine monoclonal antibodies to colon-specific antigen p.

A previous report described the production of monoclonal antibodies Mu-1, -2, -3, and -4 against colon-specific antigen p. We now report the tissue distribution of the reactive epitopes. Each of the monoclonal antibodies was reactive with epitopes shared by the entire length of the intestine, with Mu-2 and Mu-3 determinants being present in the stomach as well. Mu-1 and Mu-4 appeared to have a more restricted distribution than did Mu-2 and Mu-3, which were present in several nongastrointestinal tissues. Unfortunately, these MAbs were not ideal for in vivo use against colorectal carcinoma. Mu-1 was not present in neoplastic colon tissue, Mu-2 and Mu-4 were reactive with granulocytes, and Mu-3 was reactive with kidney tubules and connective tissue. An additional fusion was performed from which Mu-9 was selected for further study. Among normal adult tissues this monoclonal antibody gave reactivity restricted to the intestines. The stomach and all nonintestinal tissues were negative by immunoperoxidase. Among colon tumors 60% were positive for the Mu-9 epitope. The data suggest Mu-9 may be a good candidate for in vivo targeting of diagnostic and therapeutic agents to colon cancer.

Representation of epitopes on colon-specific antigen-p defined by monoclonal antibodies.

Colon-specific antigen-p (CSAp) is a large molecular-sized protein restricted to normal and neoplastic gastrointestinal tissues and to some mucinous ovarian tumors. Murine monoclonal antibodies (MAbs) were raised against CSAp that was affinity purified with goat polyclonal antibodies from GW-39 human colonic carcinoma xenografts or against the CSAp-producing colon cancer cell line SW-948. Two of the MAbs, designated Mu-2 and Mu-4, recognized a CSAp determinant containing sialic acid, and this epitope was also expressed on bovine submaxillary mucin (BSM). Blocking experiments demonstrated that the Mu-2 and Mu-4 MAbs recognized different determinants. A third MAb, Mu-3, did not cross-react with BSM, but unlike Mu-2 and Mu-4, it did react with human saliva. Reactivity of Mu-3 with saliva did not correlate with major blood group and Lewis-related secretory blood group substances in saliva. This reactivity was not related to sialylated Lewis activity. The fourth antibody, Mu-1, appeared to react with a conformational determinant since its epitope was destroyed by heat treatment or thiol reduction. Enzyme immunoassays have demonstrated that all four epitopes may be expressed on one molecular species.