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PubMed2000

Spontaneous apoptosis in advanced esophageal carcinoma: its relation to Fas expression.

The prognostic importance of spontaneous apoptosis and its correlation with clinicopathological characteristics and Fas expression have yet to be delineated in esophageal carcinoma. Specimens from 65 patients with advanced squamous cell carcinoma of the esophagus were used for immunohistochemical evaluation of Fas, proliferating cell nuclear antigen, and apoptosis. The mean apoptotic index (AI) of 65 tumors was 1.38 +/- 0.99% (range, 0.10-4.49%). Thirty-nine (60.0%) patients had a high AI, and 26 (40.0%) patients had a low AI. Low AI was correlated with advanced tumor stage (P = 0.0197) and weak Fas expression (P = 0.0093). Patients with a low AI had significantly (P = 0.0095) worse survival than those with a high AI. However, by multivariate analysis, low AI alone was not an independent prognosticator. When combined with cellular proliferation index, AI became an independent prognostic factor (P = 0.0283) in this group of patients. Our results suggest that enhanced Fas expression is responsible for high AI in squamous cell carcinoma of the esophagus. High AI, combined with the cellular proliferation labeling index, could be an independent prognostic indicator.

Age Factors↗

PubMed2001

Apoptosis index is a predictor of metastatic phenotype in patients with early stage squamous carcinoma of the tongue: a hypothesis to support this paradoxical association.

BACKGROUND: Patients with squamous carcinoma of the oral tongue in clinical stages TIN0M0 and T2N0M0 with a tumor thickness < or = 3 mm usually do not have lymph node (LN) metastasis. However, factors that are useful in predicting LN metastasis in thicker tumors (> 3 mm thick) need to be identified. The authors investigated the clinical relevance of the apoptotic index (AI), the proliferation index, and tumor grade in relation to LN metastasis in patients with early stage squamous carcinoma of the oral tongue. METHODS: Twenty-three patients with squamous carcinoma of the anterior two-thirds of the tongue measuring < 2 cm in height and > 3 mm in thickness were evaluated for tumor grade, AI (by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique), and proliferation index (by proliferating cell nuclear antigen [PCNA] expression). RESULTS: The mean AI value was significantly higher in LN positive patients compared with LN negative patients (P = 0.012). The LN positive and LN negative subgroups did not differ in the mean PCNA index, and there was no significant difference in the distributions of tumor grade between LN positive and LN negative subsets. Four of 12 tumors with an AI < or = 5% and 10 of 11 tumors with an AI > 5% had LN metastasis (P = 0.009; risk ratio, 20). The AI maintained its significance with respect to LN metastasis in the multivariate analysis (P = 0.003). The 4-year recurrence free survival was significantly better in patients with tumors that had an AI value < or = 5% compared with patients with tumors that had an AI > 5% (92% vs. 32%) (P = 0.033). However, the AI lost its impact on recurrence free survival within a Cox proportional hazards model (P = 0.068). CONCLUSIONS: A higher AI value is a predictor of LN metastasis and may serve as a prognostic factor in patients with early stage squamous carcinoma of the oral tongue. The authors present a hypothesis to explain this rather surprising finding.

Apoptosis↗

PubMed1975

[The relationships between left ventricular volumes and ejection fraction in mitral and aortic regurgitation (author's transl)].

In 2 groups of patients with mitral valvular incompetence (MI, n equals 20) and aortic valvular incompetence (AI, n equals 22) intracardiac pressures as well as left ventricular volumes (enddiastolic volume, endsystolic volume, stroke volume, ejection fraction, regurgitant volume) were determined during routine left heart catheterization and left ventriculography. Data obtained were compared with a normal group (N, n equals 20). 1. Enddiastolic volume was increased by 32 per cent (MI) and 180 per cent (AI) respectively in comparison to normal. Endsystolic volume was increased by 85 per cent (MI) and 113 per cent (AI). Total stroke volume exhibited increases by 11 per cent (MI) and 86 per cent (AI) respectively. Regurgitant volume averaged 64 per cent (AI) of total stroke volume, and 47 per cent in MI. Left ventricular ejection fraction was reduced in both groups by about 12-14 per cent. 2. enddiastolic volume was significantly dependent on the amount of regurgitant volume in both groups (MI, AI). Likewise total stroke volume increased with increments in enddiastolic volume. This increase was far mor pronounced (up to 250 per cent of normal) in AI in comparison to MI and may be referred to an effective contribution of the Frank-Starling-Straub-mechanism, induced by increased preload following regurgitation. There existed no correlation between enddiastolic volume or regurgitant volume and the effective forward stroke volume and other parameters of forward pump function (effective cardiac output, cardiac index, external cardiac work). Left ventricular compliance, as determined by diastolic pressure-volume relationships, was nearly the same in the 3 groups (N, MI, AI). 3. Left ventricular ejection fraction was nearly unchanged with increments in enddiastolic volume over a range of enddiastolic volumes up to 400 ml. At higher enddiastolic volume (is greater than 400 ml) decreases were found. In the failing heart with AI left ventricular ejection fraction was reduced even at low enddiastolic volume, exerted by decreases of fibre shortening and contractility. In contrast, in MI ejection fraction decreased with increments of enddiastolic volume over the whole range investigated. The increase in total stroke volume in both groups therefore was produced by increases of enddiastolic volume and to a very small extent by an increase of the ejection fraction. 4. The large contractility reserve in compensated AI may be referred to the altered contraction mechanism in aortic valvular regurgitation associated with i) decrese of isovolumic pressure development and increase of isotonic contraction, ii) increase of diastolic fibre stretch (preload) and iii) decrease of mean wall tension. Contractility reserve was essentially influenced by myocardial contractility. With decreases of contractility consecutively decreases of the total and the effective pump function of the left ventricle may occur despite unchanged contraction form and left ventricular dimensions.

Animals↗

PubMed2006

Genetic association study of insulin-like growth factor-I (IGF-I) gene with curve severity and osteopenia in adolescent idiopathic scoliosis.

UNLABELLED: IGF-I has a pivotal role in bone growth and could be one of the putative disease-modifier genes in AIS. Two SNPs in IGF-I gene promoter region were studied for any association with occurrence of AIS and for their effect on the curve severity among AIS. METHODS: 506 AIS girls (Cobb>20 degrees) and 227 age-matched Chinese girls were recruited. The spine (L2-L4) and hip BMD of the subjects were measured by DXA. A subgroup of AIS patients (N=340) who were followed-up to skeletal maturity and the maximum Cobb's angle was recorded. Two SNPs were genotyped by PCR-RFLP (rs5742612 and rs2288377). The chi-square test and one-way ANOVA were used to test the association between genotypes and quantitative parameters, respectively. RESULTS: No association was between the genotypes and the occurrence of AIS and the BMD of the spine and hip. The allelic frequency of T allele was 0.69 in AIS and control. However, the Cobb's angle was higher in patients with the homozygous T allele (Mean Cobb's angle: 38.1 degrees in TT vs 35.9 degrees in TC vs 33.2 degrees in CC group; p=0.04). DISCUSSION: Interestingly, IGF-I polymorphism affects the curve severity of AIS though it was not associated with onset of AIS per se. It indicates that IGF-I may be a disease modifying gene. The importance of IGF-I in skeletal growth makes it a good candidate gene which would play a role in the documented association of rapid growth with curve progression in AIS.

Adolescent↗

PubMed1989

In vitro transformation of apoA-I-containing lipoprotein subpopulations: role of lecithin:cholesterol acyltransferase and apoB-containing lipoproteins.

Two populations of apoA-I-containing lipoproteins are found in plasma: particles with apoA-II [Lp(AI w AII)] and particles without apoA-II [Lp(AI w/o AII)]. Both are heterogeneous in size. However, their size subpopulation distributions differ considerably between healthy subjects and patients with coronary artery diseases. The metabolic basis for such alterations was studied by determining the role of lecithin:cholesterol acyltransferase (LCAT) and apoB-containing lipoproteins (LpB) in the size subpopulation distributions of Lp(AI w AII) and Lp(AI w/o AII). ApoB-free and LCAT-free plasmas, prepared by affinity chromatography, and whole plasma were incubated at 4 degrees C and 37 degrees C for 24 hr. After incubation, Lp(AI w AII) and Lp(AI w/o AII) were isolated by anti-A-II and anti-A-I immunosorbents. Their size subpopulation distributions were studied by nondenaturing gradient polyacrylamide gel electrophoresis. At 4 degrees C most Lp(AI w AII) particles were in the range of 7.0-9.2 nm Stokes diameter. Incubation of plasma at 37 degrees C resulted in an overall enlargement of particles up to 11.2 nm and larger. These particles were enriched with cholesteryl ester and triglyceride and depleted of phospholipids and free cholesterol. Removal of LpB or LCAT from plasma prior to incubation greatly reduced their enlargement. At 4 degrees C, Lp(AI w/o AII) contained mostly particles of 8.5 and 10.1 nm. Incubation at 37 degrees C abolished both subpopulations with the formation of a new subpopulation of 9.2 nm. This transformation was identical in apoB-free plasma but was not seen in LCAT-free plasma. Our study shows that transformation of Lp(AI w AII) requires both LCAT and LpB. However, LpB is not necessary for the transformation of Lp(AI w/o AII) in vitro. The relevance of these in vitro studies to in vivo lipoprotein metabolism was demonstrated in a subject with hepatic triglyceride lipase deficiency.

Adult↗

PubMed1983

Effect of SQ20881 and captopril on pulmonary angiotensin II formation and blood pressure.

The lung is thought to be the major site for conversion of angiotensin I (AI) to angiotensin II (AII), although a significant amount of AI conversion is also known to occur in the peripheral circulation. Reports suggest that pulmonary conversion of AI to AII is more sensitive to inhibition by specific kininase II inhibitors than extrapulmonary conversion. This latter observation prompted us to seek for a dose of SQ20881 and/or captopril that would suppress the conversion of AI to AII in the lung without affecting extrapulmonary conversion of AI and thereby peripheral pressor responses to intravenously administered AI. Experiments were performed on 15 pentobarbital anaesthetized dogs. The AII arterial-venous difference across the lung was measured during an intravenous (i.v.) infusion of AI which produced a steady-state rise in blood pressure of 20 mmHg. This protocol was repeated with the same dose of AI following three graded doses of either SQ20881, captopril or vehicle. Results showed that the systemic pressor response to AI cannot be dissociated from pulmonary AI conversion.

Angiotensin I↗

PubMed1983

Intrinsic organization of the cat's medial geniculate body identified by projections to binaural response-specific bands in the primary auditory cortex.

The area of the cat's primary auditory cortex (AI) within which high frequency sounds are represented can be subdivided using functional criteria. Within each subdivision, or "binaural interaction band," all recorded neurons display similar responses to binaural stimulation. The current study distinguishes the thalamic sources of input to these subdivisions of AI and characterizes the topography within the thalamic projection to each class of bands. The borders of binaural bands in AI were mapped using microelectrode recording with diotic tonal stimulation, then injections of one to three retrograde tracers were introduced into identified bands. Within the ventral division (V) of the medial geniculate body (the major thalamic source of input to AI), the neuronal populations that projected to different classes of binaural bands were strictly segregated from each other. This segregation of class-specific thalamic sources constitutes a laminar organization within an axis of V that is orthogonal to the previously described tonotopic organization. Excitatory/excitatory (EE) binaural neurons in AI were found to be segregated from excitatory/inhibitory (EI) neurons in alternating "bands." We consistently identified: (1) a ventral pair of rostrocaudally continuous EI and EE bands, (2) a middle area within which the pattern of binaural subdivisions was more variable and within which bands often were discontinuous rostrocaudally, and (3) a dorsal zone (DZ) within which the responses of neurons differed in binaural properties and in frequency specificity from the response patterns that were characteristic of neurons elsewhere in AI. Each EI band apparently derived input that converged from three thickened laminae of cells in V that were oriented approximately horizontally. The most ventral of these laminae encompassed the ovoidal part of V (Vo), suggesting that EI bands are the only recipients in AI of a projection from Vo. All of the EE bands and DZ derived their input from a single continuous structure which included the dorsal two-thirds of the rostral pole of V and a horizontal lamina interposed between the two dorsalmost EI-projecting laminae. Restricted portions of the complex EE-projecting structure in V projected preferentially to particular EE subdivisions of AI. The V-to-AI thalamocortical topography exhibited a high degree of convergence and divergence within the projections to each cortical binaural band and within the projections to each class of bands. These observations indicate that the high frequency representation in AI and its principal thalamic source of input, the ventral division of the medial geniculate body, may be thought of as assemblies of spatially discrete, functionally distinguishable subunits. The significance of this intrinsic organization is discussed in regard to the requirements for analysis of sound stimuli.

Animals↗

PubMedDate not supplied

Role of endothelium in conversion of angiotensin I to angiotensin II in rabbit aorta.

Rabbit aortic rings with either an intact endothelium or a disrupted endothelium were used to generate dose response curves to angiotensin I (AI) in the presence (ED50 = 3 X 10(-7) M) and absence (ED50 = 1.7 X 10(-8) M) of 10 micrograms/ml teprotide, a converting-enzyme inhibitor. Treatment with teprotide did not alter responses to angiotensin II (AII). Comparable dose-dependent responses were obtained with AII regardless of endothelial integrity. Contraction velocities in response to angiotensin I (10(-7) M) and AII (10(-7) M) were also measured. Angiotensin II produced a significantly greater contraction velocity (p less than 0.001) than that produced by AI. The amount of conversion to AII by both intact rabbit aortic rings and rings following removal of the endothelium was determined using 125I-AI and 125I-AII. Waters C18 SEP-PAK columns were used to separate AI and AII. During the first 3 to 4 minutes after the addition of AI, contraction velocity measurements and conversion were greater in intact rings than rings without endothelium. Conversion of AI to AII in endothelial-disrupted rings was the same as in intact rings by 5 minutes after the addition of AI. Conversion of AI to AII was inhibited by 30 micrograms/ml teprotide at all times measured, and there was no evidence of an alternate route of metabolism. Angiotensin I contraction velocity measurements after 10 micrograms/ml teprotide also demonstrated impaired efficiency of conversion of AI to AII. Thus, it was established that a lack of endothelium attenuated the rate of conversion of AI to AII initially, and formation of AII with or without endothelium was blocked by teprotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMedDate not supplied

The mineral composition and enamel ultrastructure of hypocalcified amelogenesis imperfecta.

Hypocalcified amelogenesis imperfecta is characterized clinically by a yellow-brown colored enamel that is prone to severe attrition, often leading to rapid destruction of the crown. While the enamel is thought to be poorly mineralized few studies have evaluated the mineral content, or the histological or microradiographic features of this specific AI type. The purpose of this investigation was to examine teeth affected with autosomal dominant hypocalcified AI histologically using light microscopy (LM), scanning electron microscopy (SEM), and to evaluate the degree of enamel mineralization chemically and with microradiography. Four AI teeth were obtained from an affected individual for comparison with age-matched teeth from normal healthy individuals. Thin sections approximately 100 microns were cut with a diamond disc for examination by LM and microradiography. Using SEM, fractured enamel samples were examined either untreated or after removal of organic material using NaOCl or urea. Normal and AI enamel particles were dissected from thin sections to evaluate the mineral per volume and carbonate content. The enamel was not uniformly affected in all areas of the teeth with the lingual surfaces of the mandibular central incisors appearing clinically and histologically normal. The affected enamel was porous and appeared opaque with LM. Both SEM and LM showed the enamel to be prismatic with relatively normal prism morphology. However, the enamel crystallites were rough and granular compared with those of normal enamel. Extraction to remove organic material did not change the appearance of the crystallites indicating their granular appearance was due to mineral and not residual organic material such as enamel protein. Microradiography showed the enamel was less radiodense and therefore poorly mineralized compared with normal enamel. This was confirmed by chemical determination of the mineral per volume, which showed some areas of the AI enamel had as much as 30% less mineral compared with normal enamel. The carbonate content was found to be similar in AI and normal enamel. Hypocalcified AI is associated with decreased mineralization as well as ultrastructural defects in the crystallite structure. The combined histological and biochemical features of hypocalcified AI seen in this investigation indicate that this AI type is distinctly different from the hypoplastic and hypomaturation AI types.

Amelogenesis Imperfecta↗

PubMed1996

Detection of allelic imbalance indicates that a proportion of mammary hyperplasia of usual type are clonal, neoplastic proliferations.

Previously, we developed methodology for studying allelic imbalance (AI) in preinvasive breast disease and showed that AI identified at various chromosomal loci in invasive carcinoma is already present in in situ carcinoma and atypical hyperplasia. We now extend this work by looking for Ai in hyperplasia of usual type (HUT), apocrine cysts (AC), and papilloma (Pap) of the breast. HUT, AC, and Pap were identified in formalin-fixed, paraffin-embedded sections of benign breast biopsies and isolated using a microdissection technique. AI was investigated using polymorphic microsatellite markers and PCR. AI was identified in 3/23 (13%) informative cases of HUT at 17q (D17S250), 2/43 (4.7%) at 17p (D17S796), 1/22 (4.5%) at 16q (D16S413), and 0/18 (0%) at 13q (D13S267). No particular histologic feature of HUT predicted the presence of AI. No examples of AC or Pap exhibited AI at any of the markers studied. AI previously identified at various chromosomal loci in invasive carcinoma, in situ carcinoma, and atypical hyperplasia is present at low frequency in HUT in benign breast biopsies but not in AC or Pap. The possibility that AI in the latter could be masked by contamination from stromal and myoepithelial cells cannot, however, be excluded at this stage. At least a proportion of HUT thus appear to be clonal (neoplastic) rather than hyperplastic proliferations as their name suggests. The significance of AI in the pathogenesis of HUT or its subsequent progression to carcinoma is not yet clear and requires further investigation.

Alleles↗

PubMed1997

Functional organization of the auditory cortex in a native Chilean rodent (Octodon degus).

The tonotopic organization of primary auditory cortex (AI) and surrounding secondary regions has been studied in the Octodon degus using standard microelectrode mapping techniques. The results confirm and extend previous observations made in other species. The tonotopic organization of the largest field (AI) apparently covered the hearing range of O. degus. Low tonal frequencies were represented rostroventrally and high frequencies caudally, with isofrequency contours orientated dorsoventrally in a ventrocaudal slant. There were additional tonotopic representations adjacent to AI. Rostral to AI, a small field with a tonotopic gradient reversed with respect to that in AI (mirror image representation) was mapped and termed rostral auditory field (R). Best frequencies (BF's) in a range from 0.1-30.0 kHz were found in AI and R, with higher spatial resolution for the representation of lower BF's up to 10.0 kHz. Responses obtained in AI as well as in R were strong, with narrow tuning and short latencies. Caudal to AI, two small additional, tonotopically organized fields, the dorsoposterior field (DP) and the ventroposterior field (VP), could be distinguished. In fields VP and DP, high BF's were situated rostrally, adjacent to the high frequency representation in AI. Low frequency representations were found in caudal part of DP and VP fields. Responses to tone burst within DP and VP were mostly weak, with longer latencies and broader tuning compared to those found in AI and R.

Acoustic Stimulation↗

PubMed1993

The Roscommon Family Study. IV. Affective illness, anxiety disorders, and alcoholism in relatives.

OBJECTIVES: This report seeks to evaluate the specificity of the familial liability to schizophrenia by examining in the relatives of the various proband groups the risk for affective illness (AI), anxiety disorders, and alcoholism. DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. PARTICIPANTS: Three hundred eighty-four index probands from a psychiatric case register, 150 unselected control probands from an electoral register and 2043 of their living and traceable relatives, of whom 1753 were personally interviewed. RESULTS: In personally interviewed relatives of schizophrenic probands, the lifetime risk for all AI (24.9% +/- 3.8%) or just bipolar AI (1.2% +/- 0.7%) was very similar to that found in interviewed relatives of controls (22.8% +/- 4.0% and 1.4% +/- 0.7%, respectively). However, the risk for all AI (49.7% +/- 12.9%) or bipolar AI (4.8% +/- 3.2%) was substantially increased in relatives of schizoaffective probands. A substantially higher proportion of relatives of schizophrenic vs control probands who had AI demonstrated psychotic--and specially mood-incongruent psychotic--symptoms when affectively ill. Neither the risk for anxiety disorders nor that for alcoholism was increased in relatives of schizophrenic vs control probands. CONCLUSIONS: The familial liability to schizophrenia possesses some specificity and does not substantially increase the risk to AI, anxiety disorders, or alcoholism. Even when narrowly defined, schizoaffective disorder has a substantial familial link to classic AI. The familial liability to schizophrenia predisposes to psychosis, and especially mood-incongruent psychosis, when affectively ill. Finally, these results do not support the hypothesis that, from a familial perspective, schizophrenia and AI are on a single etiologic continuum.

Adolescent↗

PubMed1997

Endocervical adenocarcinoma in situ: an analysis of cellular features.

Cytologists increasingly encounter atypical endocervical cells, because of the increasing incidence of endocervical adenocarcinoma and the use of improved endocervical sampling devices. These atypical endocervical cells can cause diagnostic problems, especially in recognizing adenocarcinoma in situ (AIS) and distinguishing it from a variety of nonneoplastic changes. We analyzed 33 cervical smears from 22 patients with confirmed AIS and compared these to 19 cervical smears from 17 patients having atypical endocervical cells of undetermined significance and negative follow-up, including at least one tissue biopsy per case, to further investigate the cytologic features of AIS. The AIS smears typically had crowded three-dimensional cellular aggregates, with markedly hyperchromatic nuclei having altered polarity. Frequently, a minor component of AIS formed strips of distinctly columnar cells or sheets. Individual AIS cells occurred in 22 (67%) smears, but these were usually inconspicuous. The AIS smears also had increased nuclear to cytoplasmic ratios (100%), enlarged nuclei (94%), feathering (88%), rosettes (85%), nucleoli (76%), apoptosis (73%), mitoses (64%), multiple nucleoli (18%), and ciliated atypical cells (3%). Cytologic features occurring significantly (P < or = 0.001) more often in AIS cases were a predominance of three-dimensional crowded aggregates (79% vs. 32%), altered nuclear polarity in most groups (88% vs. 16%), marked hyperchromasia (91% vs. 16%), apoptosis (73% vs. 26%), an increased nuclear to cytoplasmic ratio (100% vs. 63%), feathering (88% vs. 26%), and individual atypical cells (67% vs. 16%). In summary, we identified a number of architectural and cellular features that occurred significantly more often in AIS cases than in cases having atypical endocervical cells of undetermined significance and negative follow-up.

Adenocarcinoma↗

PubMed2000

Projections from the medial geniculate body to primary auditory cortex in neonatally deafened cats.

In the present study, anatomical projections from the medial geniculate body (MGB) to primary auditory cortex (AI) were investigated in normal adult cats and in animals that were neonatally deafened with the ototoxic drug amikacin. Cochleotopic/tonotopic maps in AI (based on neural response characteristic frequency) were obtained with microelectrode recording techniques, and single or multiple injections of retrograde tracers (horseradish peroxidase and fluorescent dyes) were introduced into AI. The AI maps of the amikacin-treated cats had an abnormal cochleotopic organization, such that deprived cortical areas exhibited an expanded representation of intact regions of the damaged cochlea. However, retrograde tracer injections into different regions of AI produced a normal pattern of labeling in the ventral division of the medial geniculate body (MGBv). In both experimental and control animals, the main mass of labeled thalamic cells was found in the MGBv. Different isofrequency contours in AI receive input from different portions of the MGBv. Thus, cell arrays labeled by anterior AI injections were situated medially in MGBv, and injections into posterior AI labeled MGBv more laterally. Furthermore, the deafened cats did not develop a more divergent thalamocortical projection compared with normal control animals, indicating that an abnormal spread of the thalamocortical afferents across the frequency domain in AI (anterior-posterior axis) is not responsible for the altered cochleotopic map in these neonatally deafened animals. The relatively normal thalamocortical projection pattern suggests that, after neonatal cochlear lesions, the major reorganization of cochleotopic maps occurs at subthalamic levels.

Age Factors↗

PubMed2000

Primary cervical carcinomas show 2 common regions of deletion at 3P, 1 within the FHIT gene: evaluation of allelic imbalance at FHIT, RB1 and TP53 in relation to survival.

Chromosome arm 3p is re-arranged in many tumor types, including cervical carcinomas. Putative tumor-suppressor genes on 3p have been proposed, including the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was evaluated after immunohistochemistry with an antibody against the pFHIT protein. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest regions of overlapping deletion (SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT loci (p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse-free survival was associated with AI in the TP53 gene in both a univariate (p = 0.0003) and a multivariate (p = 0.004) analysis. This study confirms a high frequency of AI at chromosome arm 3p in primary cervical carcinomas. The AI results and the reduced FHIT protein staining indicate that FHIT alterations are important in cervical carcinogenesis.

Acid Anhydride Hydrolases↗

PubMed2004

Severe cervical glandular cell lesions and severe cervical combined lesions: predictive value of the papanicolaou smear.

BACKGROUND: The purpose of the current study was to determine the accuracy of routinely screened cervical smears to predict a glandular cell lesion in histologically confirmed cases of cervical adenocarcinoma in situ (AIS), invasive adenocarcinoma (ADCA), adenosquamous carcinoma (ADSQCA), and severe combined glandular and squamous cell lesions. METHODS: Between 1989-2000, a total of 1,141 women with a histologic diagnosis of cervical AIS, ADCA, ADSQCA, and combined lesions (glandular cell lesion with a coexistent squamous cell lesion) were registered in the Dutch National Pathology Archive (PALGA). In 1054 of these 1,141 histologic cases, an additional conventional Papanicolaou (Pap) smear diagnosis was registered from the same patient. Material was evaluated with regard to the accuracy of cytologic diagnosis, the percentage of combined lesions, the mean age of the patients, and the time interval between AIS and ADCA. RESULTS: Of 1,141 registered histologic cases, 57.5% were registered as having an "intraepithelial" lesion, whereas 42.5% were registered as having an "invasive" process. A combined process was diagnosed in 63.2% of cases. From the same patients, a cytologic diagnosis of a severe cervical epithelial lesion was registered in PALGA for 91.2% (n = 961) of 1054 cases. A cytologic registration of a severe glandular cell lesion (with or without a squamous cell component) was made in 547 cases (51.9%). Prediction of a severe glandular cell lesion on the Pap smear was found to be more accurate in cases of histologically confirmed pure glandular cell abnormalities than in cases with a histologic diagnosis of a combined lesion. The cytologic prediction was found to be correct in 75.2% of cases of pure AIS and 47.3% of cases of AIS with coexistent high-grade squamous intraepithelial lesion (HGSIL) (cervical intraepithelial lesion [CIN] type 2 [CIN 2] or CIN 3). The mean ages of the patients with AIS and AIS + HGSIL were 37.3 years and 34 years, respectively, whereas the mean age of the patients with ADCA and ADCA + HGSIL was 41.9 years and 38.1 years, respectively. The interval between the average ages of patients with AIS and ADCA and those with AIS + HGSIL and ADCA + HGSIL was 4.6 years and 4.1 years, respectively. CONCLUSIONS: On the basis of a data search of the PALGA registry, it can be concluded that in a relatively large number of cases a severe cervical glandular cell lesion was not diagnosed on the Pap smear. Furthermore, data demonstrated that the prediction of a glandular abnormality is less accurate in cases of combined squamoglandular cell lesions than in pure glandular cell lesions.

Adenocarcinoma↗

PubMed1985

Neuronal connections in the primary auditory cortex: an electrophysiological study in the cat.

Neuronal connections in the primary auditory cortex (AI) of the cat were studied electrophysiologically by using intracellular recording techniques. Fast-conducting fibers from the medial geniculate nucleus (MG) projected monosynaptically onto AI neurons in layers III-VI (mainly in layer IV), whereas slow-conducting MG-fibers projected monosynaptically onto AI neurons in layer I. AI neurons which received monosynaptic inputs from the auditory association cortices (AII and Ep) and/or from the contralateral AI were distributed in all layers of the AI; the commissural fibers from the contralateral AI were divided into fast- and slow-conducting ones. AI neurons were categorized into seven types: type I neurons which received monosynaptic inputs from slow-conducting MG-fibers were located in layer I. Type II neurons which received polysynaptic inputs from the MG were located in layers II-VI. Type III neurons which sent their axons to the AII or Ep were mainly located in layer III. Type IV neurons which sent their axons to the contralateral AI were located mainly in layer III. Type V neurons which received monosynaptic inputs from fast-conducting MG-fibers were located mainly in layer IV. Type VI neurons which projected onto the inferior colliculus were located in the upper part of the layer V. Type VII neurons which projected onto the MG were located in layers V and VI.

Animals↗

PubMed1975

The association connexions of the suprasylvian fringe (SF) and other areas of the cat auditory cortex.

The association connexions of the peri-auditory (SF, Ea and INS) and auditory (AI, AII and Ep) areas of the cat cortex were studied in silver impregnated material of 32 experiments with cortical lesions. The cortex of the lateral bank of the rostral part of the middle suprasylvian sulcus (SF) sends many fibres to AI and to the insular cortex (INS), and has scanty projections upon AII and Ep. In addition, it sends fibres to the visual area 17 as well as to the ventral bank of the medial part of the cruciate sulcus. It receives fibres from the three auditory areas AI, AII and Ep, as well as from Ea and INS. The dorsal part of the anterior ectosylvian gyrus (Ea) projects upon SF, AI, and AII. Ea sends few fibres to Ep, and receives relatively dense projections from AI and AII. The anterior sylvian gyrus (INS) projects heavily upon AII as well as upon the superficial part of SF. It sends a few fibres also to Ep. INS receives heavy projections from AII and relatively lighter connections from SF, AI and Ep. The three auditory areas AI, AII and Ep are strongly mutually interconnected. AI and Ep have scanty projections upon the visual area 19, and AI also to the lateral suprasylvian visual area, as well as upon the ventral bank of the medial cruciate sulcus. Correlations of the association connexions with the functions of each area are discussed.

Animals↗