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A Stella

Publications and source records attributed to A Stella.

At least 19 recordsLinked to original sources
PubMed2000

Oxytocin receptors in human adenocarcinomas of the endometrium: presence and biological significance.

Oxytocin receptors (OTRs) are expressed in endometrial cells and oxytocin (OT) participates in endometrial functions. In cancers derived from other OT target tissues, such as breast and neural tissues, the expression of OTRs and the antiproliferative effect of OT on cancer cells has been previously observed. This study was therefore designed to search for OTR expression and the OT effect in endometrial carcinomas. To demonstrate the presence and the location of OTRs and OTR mRNA immunocytochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) procedures were employed in a series of human adenocarcinomas of the endometrium. Using an anti-OTR monoclonal antibody (IF3), OTRs were demonstrated in the large majority of endometrial carcinomas (82%), with a pattern of positivity varying from diffuse to focal, according to tumour differentiation. The OTR gene was demonstrated in 78% of the cases by RT-PCR and its presence was confirmed in selected cases by ISH. Moreover, in a human endometrial carcinoma cell line (COLO 684) OTR was demonstrated by immunofluorescence and RT-PCR and it was observed that OT treatment (10(-11)-10(-7) M) significantly inhibited cell proliferation. Neither toxic effects nor apoptosis were induced by OT treatment. The addition of an inhibitor of protein kinase A (PKA) to the culture medium abolished the antiproliferative effect of OT, suggesting that cAMP via PKA could be the intracellular mediator of the OT effect, as previously observed in breast and neural tumours. In conclusion, this study presents evidence of OTR expression in human endometrial carcinomas and of an OT antiproliferative effect on human endometrial cancer cells in vitro. It is further suggested that OT and OTR may be involved in the regulation of endometrial cells, not only in physiological conditions but also in a neoplastic context.

Adenocarcinoma↗
PubMed2000

Effects of adenosine receptor agonists on efferent renal nerve activity in anesthetized rats.

The aim of this study was to investigate the effects of A1 and A2 adenosine-receptor activation on the sympathetic nervous system. The effects on efferent renal nerve activity of selective A1 (CCPA; 2-chloro-N-6-cyclopentyladenosine) and A2 (2HE-NECA; 2-hexynyl-5'-N-ethylcarboxamidoadenosine) adenosine-receptor agonists were studied in anesthetized rats either with intact baroreflexes (intact rats) or with bilateral sinoaortic denervation and vagotomy (denervated rats). After a control period of 5 min, A1 or A2 agonist or vehicle were intravenously infused for 8 min in separate groups of intact or denervated rats, in which arterial pressure and heart rate were continuously recorded. CCPA (5.0 microg/kg/min) and 2HE-NECA (0.7 microg/kg/min) were selected to obtain comparable blood pressure changes over the period of observation. Arterial pressure significantly and equally decreased during the A1 (-41 +/- 8%), and A2 (-35 +/- 5%) agonist administration. Heart rate significantly decreased during A1 agonist infusion, but it did not change during A2 agonist administration. Bilateral sinoaortic denervation and vagotomy did not modify the hemodynamic responses to both drugs. The A1 and A2 administration caused a large and significant increase in efferent renal nerve activity (+66 +/- 22% and +76 +/- 15%, respectively), and this effect was entirely abolished in denervated rats. A linear relation with a significant negative slope between changes in arterial pressure and changes in neural discharge was observed for each treatment. The comparison of the regression slopes showed that the reflex increase of efferent sympathetic activity caused by the administration of both agonists was significantly smaller than the increment induced by equipotent hypotensive dose of sodium nitroprusside (10 microg/kg). These data show that the selective activation of A1 and A2 receptors elicits a reflex increase in efferent renal nerve activity. This neural activation is smaller as compared with the effect of equihypotensive doses of sodium nitroprusside, thus indicating a blunting effect of both adenosine agonists on baroreceptor sensitivity.

Adenosine↗
PubMed2000

Short-term analysis of the relationship between blood pressure and urinary sodium excretion in normotensive subjects.

The aim of this study was to investigate whether, in the short term, physiological blood pressure changes are coupled with changes in urinary sodium excretion in normotensive subjects, maintained at fixed sodium intake and under controlled postural and behavioural conditions. Twelve normotensive subjects were recruited. For each subject, seven urine samples were collected at fixed time intervals during an overall 26 h period: late afternoon (16.00-20.00 hours), evening (20.00-24.00 hours), night (24.00-06.00 hours), quiet wakefulness (06.00-09.00 hours), morning (09.00-12.00 hours), post-prandial (12.00-15.00 hours) and afternoon (15.00-18.00 hours). Blood pressure was monitored by an ambulatory blood pressure device during the whole 26 h period. Each urine sample was used to measure urinary sodium excretion and glomerular filtration rate (creatinine clearance). Blood pressure, heart rate, urinary sodium excretion and glomerular filtration rate recorded in the daytime were higher than those measured during the night-time. A significant positive correlation between mean blood pressure and urinary sodium excretion was found during the night, over the whole 26 h period, and during two subperiods of the daytime: quiet wakefulness and the post-prandial period. The coefficient of the pressure-natriuresis curve was significantly decreased by postural changes. We conclude that, in normotensive subjects, blood pressure and urinary sodium excretion are coupled in the short term. The assumption of an upright posture can mask this relationship, presumably by activating neurohumoral factors.

Adult↗
PubMed1999

Bioactive IL-18 expression is up-regulated in Crohn's disease.

An imbalance of immunoregulatory factors is believed to contribute to uncontrolled mucosal Th1 cell activation in Crohn's disease (CD). IL-18, a macrophage-like cell-derived cytokine, is involved in Th1 clone development, and IFN-gamma production. Therefore, IL-18 expression was investigated in CD. Whole mucosal intestinal tissue and lamina propria mononuclear cells (LPMC) of 12 CD and 9 ulcerative colitis (UC) patients and 15 non-inflammatory bowel disease (IBD) controls were tested for IL-18 by semiquantitative RT-PCR and Western blot analysis. Transcripts for IL-18 were found in all samples tested. However, increased IL-18 mRNA accumulation was detected in both mucosal and LPMC samples from CD in comparison to UC and controls. In CD, transcripts for IL-18 were more abundant in the mucosal samples taken from involved areas. An 18-kDa band consistent with mature IL-18 was predominantly found in CD mucosal samples. In mucosal samples from non-IBD controls, IL-18 was present as a 24-kDa polypeptide. Consistently, active IL-1beta-converting enzyme (ICE) subunit (p20) was expressed in samples from either CD or UC, whereas, in colonic mucosa from non-IBD controls, ICE was synthesized as precursor (p45) only. To confirm that IL-18 produced in CD tissue was functionally active, CD LPMC were treated with a specific IL-18 antisense oligonucleotide. In these cultures, IL-18 down-regulation was accompanied by a decrease in IFN-gamma expression. In aggregate, our data indicate that IL-18 up-regulation is a feature of CD and suggest that IL-18 may contribute to the local immunoinflammatory response in CD.

Caspase 1↗
PubMed1999

Comparison of clinical and demographic features between affected pairs of Italian multiple sclerosis multiplex families; relation to tumour necrosis factor genomic polymorphisms.

We conducted a comparative analysis of clinical and demographic findings between pairs of relatives (36 sibling and 9 parent/child), concordant for Multiple Sclerosis (MS), from 40 MS Italian Multiplex families. A genetic TNF (alpha and beta) loci typing in 51 affected and 69 healthy relatives belonging to 25 of these families was also performed. The sib pairs resulted significantly concordant for age at onset (r=0.414, P<0.013), Progression Index (r=0.34, P<0.05) and sensory symptoms at onset (k=0.37), and significantly not concordant for sex (k=-0.37), whereas no concordance was found for year at onset and disease course. The only significant result in the small group of parent/child pairs was that parents developed MS at an age of 18.74 years significantly (P=0.020) greater than their children. Genomic analysis identified 13 variants of TNF-a alleles, 7 of TNF-b, 6 of TNF-d and 3 of TNF-e. No differences in the frequencies of the various TNF alleles were observed between affected and healthy relatives. The two-point lod-score analysis of the TNF locus showed not significant or negative results for the TNFalpha loci and slightly positive results (Zmax=0.4 at theta=0.2 cM) for the TNFbeta-b locus in the lowest penetrance dominant model. The Sib pair analysis, using combined TNFalpha and TNFbeta haplotypes, demonstrated a TNF allele sharing between affected sib-pairs which did not exceed the expected 50%. These results suggest that genetic factors may partially influence the disease onset and the progression rate in sibling pairs. A recall bias and/or an 'anticipation phenomenon' could explain the development of MS at an older age in parents than in their children. In this small-sized cohort of MS Italian families no significant associations were confirmed between TNF polymorphism and MS.

Adult↗
PubMed1999

Predictive markers of pre-eclampsia in hypertensive disorders of pregnancy.

OBJECTIVE: The aim of this work is to assess the most widespread methods currently proposed and two new markers for predicting the development of pre-eclampsia in pregnant women with hypertension. METHODS: The study involved 212 pregnant Caucasian women: 104 normotensive, 68 pregnancy-induced hypertensive and 40 chronic hypertensive. Blood and urine were sampled between 28 and 30 weeks gestation. All 108 hypertensive pregnant women, at the time of sampling, demonstrated proteinuria below 0.3 g/24 h. The following laboratory tests were performed: fibronectin, antithrombin-III, alpha-1-microglobulin, U-N-acetyl-beta-glucosaminidase, uric acid and albumin excretion rate. Student's t-test, discriminant analysis and chi2 (chi-square) test were used as statistical methods. A P value less than 0.05 was considered significant. RESULTS: After discriminating analysis, only three of the six variables analyzed were able to discriminate patients who would develop pre-eclampsia from the remaining hypertensive pregnant women: microalbuminuria, uric acid and fibronectin (chi2 = 29.122, P < 0.01). CONCLUSIONS: In agreement with previous studies, albumin excretion rate appeared to be the best predictive test for pre-eclampsia in hypertensive pregnant women, giving a higher positive predictive value and specificity (87.5 and 98.9%, respectively).

Adult↗
PubMed1999

Immune response following fresh arterial homograft replacement for aortoiliac graft infection.

INTRODUCTION: this prospective study defines the immune response to fresh arterial homograft replacement for graft infection. MATERIALS AND METHODS: ten patients who underwent ABO-compatible homograft transplantation were studied for anti-HLA antibody production, and CD3-CD4-CD8-positive lymphocytes subset. Immunological studies were performed preoperatively, and at early (1, 3, 7 days) and late (1, 3, 6, 12, 18, 24 months) follow-up. All patients received immunosuppressive treatment with cyclosporine (1-3 mg/kg/day). Abdominal CT scans were performed postoperatively at the 1, 6, 12, 18, 24 months follow-up. RESULTS: preoperatively, antibodies could not be detected. Postoperatively, as from 1st month post-transplant, a progressive increase in % PRA was observed in all patients, up to the 12th month of follow-up. Subsequently, at 18 and 36 months, a progressive decrease in % PRA was detected. Data showed that the recipient antibodies were directed against donor-specific antigens. During the immediate postoperative period (1, 3, 7 days) CD3- and CD4-positive T lymphocytes slightly increased, whereas CD8 simultaneously decreased. Later, CD3 and CD4 progressively decreased and CD8 increased. Clinically, all patients were cured of infection at late follow-up. CT scans showed thickening of the aortic wall (range: 2.5-4.5 mm), with no signs of aneurysmal degeneration. CONCLUSIONS: fresh arterial homografts are immunogenic. Implanted homografts induce a strong anti-HLA antibody response, similar to chronic rejection, in spite of immunosuppressive treatment.

ABO Blood-Group System↗
PubMed1999

Cardiovascular disease and the kidney: an epidemiologic overview.

Essential hypertension and congestive heart failure (CHF) are examples of cardiovascular disorders that may cause renal failure, although sometimes a primary kidney defect may lead to hypertension. Renal damage in malignant and severe hypertension is dramatic, extensive, and rapidly progressive, although nephrosclerotic damage, which develops slowly and appears late in hypertension, is a rare cause of morbidity because mild to moderate hypertension is now the most common form. However, the incidence of end-stage renal failure associated with hypertension is markedly increasing, perhaps because of underdiagnosis of renal damage in hypertension, insufficient lowering of blood pressure in clinical practice, or inability of antihypertensive drugs to lower blood pressure sufficiently to preserve the kidney, a goal that may need specific drugs that act, for example, on the renin-angiotensin system (RAS). Renal vasoconstriction and reduction of renal blood flow are early companions of cardiac insufficiency and may be involved in the development of sodium and water retention. Profound reduction of cardiac output and arterial hypotension in severe CHF may lead to acute renal failure. Chronic renal insufficiency is associated with elevated cardiovascular morbidity and mortality. Renal impairment is often caused by a disease process, such as diabetes mellitus, that involves both the cardiovascular system and the kidney. When the primary disease is renal, possible reasons for an association include renal-dependent increase in blood pressure, activation of the RAS, overproduction of other vasoactive substances of renal origin, and electrolyte imbalances leading to fatal arrhythmias.

Animals↗
PubMed1999

Colorectal cancer and the Muir-Torre syndrome in a Gypsy family: a review.

OBJECTIVES: The Muir-Torre syndrome (MTS) is characterized by an autosomal dominant predilection to sebaceous adenomas, sebaceous carcinomas, and multiple keratoacanthomas, in concert with the cancer phenotype of hereditary nonpolyposis colorectal cancer (HNPCC). Proof that patients showing a familial aggregation of MTS's cutaneous signs in combination with a specific pattern of visceral cancers which are consonant with an HNPCC diagnosis has been buttressed by the discovery of hMSH2 and hMLH1 germ-line mutations in such families. Our purpose in this investigation was to determine the germ-line mutation in a Gypsy family with MTS in concert with HNPCC cancer features, and to provide genetic counseling. An added objective for this paper is to review the literature on MTS. METHODS: We describe a Gypsy family with MTS in concert with HNPCC cancer features, as well as the molecular genetic and genetic counseling procedures used in the interest of improved compliance with cancer control recommendations. We review the clinical phenotype, natural history, and molecular genetics involved in the MTS variant HNPCC. RESULTS: An hMSH2 germ-line mutation was identified as the culprit germ-line mutation in this family. CONCLUSIONS: The presence of the hMSH2 germ-line mutation in this family provides powerful predictability of colorectal and other HNPCC integral cancers. The gastroenterologist must assume an important role in the diagnosis and management of MTS.

Adult↗
PubMed1999

Iodide symporter gene expression in normal and transformed rat thyroid cells.

OBJECTIVE: Decrease or loss of the Na+/I- symporter (NIS) activity profoundly affects the suitability of the use of radioiodine to detect or treat metastatic thyroid tissues. The aim of our study was to verify whether specific oncogene abnormalities were responsible for the alteration in NIS activity in thyroid cells. DESIGN AND METHODS: Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with different degrees of malignancy which had lost the iodide uptake ability. RESULTS: NIS gene expression was up-regulated by TSH in a dose-dependent and time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely, insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory effect on NIS gene expression. The oncogene-transformed cell lines PC v-erbA, PC HaMSV, PC v-raf, and PC E1A cells showed reduced NIS mRNA levels compared with the normal PC Cl 3 cells. Conversely, an almost complete absence of NIS gene expression was found in PC RET/PTC, PC KiMSV, PC p53(143ala), and PC PyMLV cell lines. CONCLUSIONS: Our data show that oncogene activation could play a role in affecting the iodide uptake ability in thyroid tumoral cells; different mechanisms are involved in the oncogene-dependent loss of NIS activity in transformed thyroid cells.

Animals↗
PubMed1999

Role of the renal nerves and angiotensin II in the renal function curve.

The relationship between renal perfusion pressure and urinary sodium is involved in arterial pressure regulation. The aim of this study was to investigate the role of renal nerves and angiotensin II in the pressure-natriuresis relationship. Experiments were performed in anaesthetised cats in which one kidney was surgically denervated. Renal perfusion pressure (RPP), renal blood flow (RBF) glomerular filtration rate (GFR, creatinine clearance), urinary volume (V) and sodium excretion (Una + V) were separately measured from both kidneys. RPP was progressively reduced in two consecutive steps by a suprarenal aortic snare. Two groups of animals were studied: the first without any pharmacological treatment (Untreated), the second during treatment with an angiotensin converting enzyme inhibitor (Captopril, 0.4 mg/Kg intravenously followed by an infusion of 0.4 mg/Kg/h). In the Untreated group RPP was reduced from 152.4 +/- 7.3 to 113.6 +/- 5.8 and 83.0 +/- 4.4 mmHg during the first and second step respectively. RBF and GFR were only slightly reduced during the second step of reduced RPP. In control conditions V and UNa + V were greater in the denervated compared to the innervated kidney. The graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. In the Captopril group V and UNa + V were larger than in the Untreated group in both the innervated and the denervated kidney. A decrease of RPP similar to that observed in the Untreated group, produced similar haemodynamic changes. Also in the Captopril group the graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. Matching UNa + V against RPP values significant correlations were found in the innervated and denervated kidneys of both groups. Both renal denervation and ACE inhibition were accompanied by an increased gain of the pressure-natriuresis curve, but only renal denervation shifted the crossing of the pressure axis to the left. In the ACE inhibited animals renal denervation only shifted the curve to the left. In conclusion our data suggest that i) at each level of RPP renal nerves and angiotensin II decrease renal sodium excretion, ii) renal nerves and angiotensin II increase the slope of the renal function curve, iii) renal nerves shift to the right the renal function curve.

Angiotensin II↗
PubMed1999

Markers of tubular damage in pre-eclampsia.

BACKGROUND: The aaim of this study is to investigate the tubular damage markers in pre-eclampsia and in pregnancy induced hypertension (PIH). METHODS: This transversal study involved 111 women admitted to the Department of Obstetric and Gynaecology, University Hospital, Padua (Italy) and was conducted from the 24th week until delivery: 23 had normal pregnancies, 54 manifest pre-eclampsia, and 34 manifested pregnancy-induced hypertension (PIH) without superimposed pre-eclampsia. The following laboratory tests were performed: U-alpha 1 microglobulin, U-NAG, uric acid and microalbuminuria. The four groups were compared using the Mann-Whitney test and the Kruskall-Wallis test for multiple comparisons. A value of p < 0.05 was considered as statistically significant. RESULTS: As for the markers of tubular damage, the values for urinary NAG were significantly lower in the control group (0.97 U/mmol Creat) than in the pre-eclampsia group (2.89 U/mmol Creat), and the PIH group (2.12 U/mmol Creat) (p < 0.01). Values for urinary alpha 1-microglobulin were higher in the pre-eclampsia group (4.03 U/mmol Creat) than in the control (0.74 U/mmol Creat), and PIH groups (1.88 U/mmol Creat) (p < 0.01). As for the markers of glomerular damage, the values of microalbuminuria were higher in the pre-eclampsia group (134 micrograms/min) than in the control (9.4 micrograms/min), and PIH groups (10 micrograms/min), (p < 0.05). Uric acid, the marker of glomerular and tubular damage, was higher in the pre-eclampsia group (0.27 mmol/L) than in the control (0.20 mmol/L), and PIH groups (0.24 mmol/L), (p < 0.05). CONCLUSIONS: In pre-eclampsia there is a tubular and glomerular damage to point out by an increased urinary excretion of NAG. In pre-eclampsia, an increase of urinary alpha 1-microglobulin excretion may be considered to be partly due to the overloading of the tubule and partly due to a mixed glomerular and tubular lesion.

Acetylglucosaminidase↗
PubMed1998

Presence and significance of oxytocin receptors in human neuroblastomas and glial tumors.

To determine whether oxytocin (OT) could be added to the list of growth factors acting on neoplastic cells of nervous origin, we investigated the presence of oxytocin receptors (OTR) in human primary neuroblastomas and glioblastomas and related cell lines. OTR were demonstrated both at mRNA level (using a RT-PCR procedure) and at protein level (using immunocytochemical and immunofluorescence procedures). In order to clarify whether OT exerts any biological effect on these tumors through OTR, we also studied cell proliferation in 3 human neuroblastoma cell lines (SK-N-SH, SH-SY5Y, IMR-32) and one human anaplastic astrocytoma cell line (MOG-G-UVW) treated with OT 1 nM to 100 nM for 48 and 96 hr. At these doses, a dose-dependent inhibitory effect on cell proliferation was demonstrated. This inhibition was accompanied by a significant increase in the intracellular concentration of cAMP, which we have reported to be the intracellular mediator of the OT anti-proliferative effect in breast-carcinoma cell lines. Our data indicate that specific OTR are present in human neuroblastomas and glioblastomas. Through these receptors, OT could inhibit cell proliferation and modulate tumor growth.

Brain Neoplasms↗
PubMed1998

Chromogranin A gene expression in non-small cell lung carcinomas.

Evidence for the existence of neuroendocrine (NE) differentiation in non-small cell lung carcinomas (NSCLCs) is at present based on histochemical, ultrastructural, and immunohistochemical data. The aim of this study was to investigate the extent of NE differentiation in NSCLCs as revealed by mRNA analysis. Different techniques including immunohistochemistry (IHC), northern blot analysis (NBA), and reverse transcriptase-polymerase chain reaction (RT-PCR) were employed in parallel to reveal the panendocrine marker chromogranin A (CgA). The data were related to pathological, immunocytochemical (PGP 9.5, synaptophysin, Leu-7 and neuron-specific enolase), and prognostic indicators. Forty surgically resected cases of NSCLC (24 squamous cell carcinomas, 12 ordinary type adenocarcinomas, 3 bronchiolo-alveolar carcinomas, and 1 anaplastic large cell carcinoma), in which fresh frozen material was available for mRNA analysis, were collected. CgA immunoreactivity was present in five cases (12.5 per cent), generally confined to a minority of the neoplastic cell population. By RT-PCR, CgA mRNA was found in 20 cases (50 per cent), including the five tumours positive by IHC. A statistically significant correlation was found between the two techniques. By NBA, no CgA mRNA expression was detected. Leu-7 immunoreactivity was present in 15 per cent of cases, NSE in 52.5 per cent, synaptophysin in 10 per cent, and PGP 9.5 in 82.5 per cent. In NSCLC, no correlations were found between CgA production, as detected by IHC or RT-PCR methods, and the histological type, stage, grade and proliferative activity of tumours, or the disease-free interval. It is concluded that CgA gene expression can be revealed in NSCLC at both mRNA and protein levels and that RT-PCR is a valuable tool for identifying NE differentiated NSCLCs. Our data suggest that NE differentiation does not represent an independent prognostic factor in surgically resected NSCLCs.

Adult↗
PubMed1998

Relief of transcriptional polarity by a mutation that creates a promoter in the hisG gene of Salmonella typhimurium LT2.

Six mutant strains were independently isolated in Salmonella typhimurium as non-polar revertants of a polar Tn10 insertion in hisG. DNA sequence analysis showed that all six mutants result from the same nucleotide alteration: a G/C to A/T transition 4 bp from the end of the hisG coding sequence. We present data suggesting that the mutation (hisG10225) acts by creating a new transcriptional initiation signal. Furthermore, the hisG10225 mutation renders the hisG gene product cold sensitive.

Bacterial Proteins↗
PubMed1998

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

Antibodies↗
PubMed1998

The familial adenomatous polyposis region exhibits many different haplotypes.

In the present study, we used five different polymorphic markers to construct the haplotype at the adenomatous polyposis coli (APC) locus in families with familial adenomatous polyposis (FAP) and in the normal Italian population. Non-ambiguous haplotypes were reconstructed from 246 normal chromosomes and 65 FAP chromosomes. In the control population, the four polymorphisms intragenic to APC gave rise to 16 haplotypes, the most common of which (II and XV) accounted for over 50% of all chromosomes. In FAP patients, 13 haplotypes were found but their distribution was not statistically different from normal subjects. Eighty complete chromosomal haplotypes (many fewer than the theoretical maximum of 208) for the five polymorphic sites assayed were observed in the control population, 35 being found in the FAP patients. We compared the distribution of these haplotypes within the two groups; no statistically significant differences between normal and FAP chromosomes were found. The elevated heterogeneity of FAP chromosomes was clearly confirmed by the observation that 19 patients who carried one or other of the two most common APC mutations (nt 3183 and nt 3927) showed 18 different haplotypes. On the basis of these results, we were not able to identify a founder FAP chromosome. Various mechanisms are presented to explain this observation.

Adenomatous Polyposis Coli↗