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Influence of the surgical treatment on local recurrence of rectal cancer: a prospective study (1980-1992).

BACKGROUND AND OBJECTIVES: The incidence of locoregional recurrences (LR) following radical surgery of rectal cancer varies from 5% to 30% according to the literature. The purpose of this prospective study was to compare the outcome of the Abdomino-Perineal Excision (APE) vs. the Anterior Resection (AR) in a consecutive series of 188 patients who underwent surgery for cure from 1980 to the end of 1992 (81 APE and 107 AR), followed for 5 years, evaluating their influence on the incidence of the recurrences. METHODS: The patients were enrolled at random in the two surgical groups, provided that a radical excision of the tumour, with only two limits: the level of the lesion from the anal verge and the presence of a severe incontinence instrumentally proven. TNM, Dukes staging, grading, and tumour location were statistically evaluated. Further primary suture vs. packing of the perineal wound in APE and handsewn vs. stapled anastomosis in AR were compared in relation with the incidence of LR. RESULTS: The overall local recurrence rate was 19.2% (32/167), in details 19.7% for APE and 18.5% for AR. Similar recurrence rates were observed following both procedures, matching the patients according to the Dukes stage and different details of techniques. A slight statistically significant difference was found as far as the tumour location is concerned in the group treated with anterior resection (p = <0.05) because of the higher recurrence observed in AR performed for tumours of the lower third of the rectum in comparison with the more proximal level. CONCLUSIONS: The AA conclude that the choice of the right surgical procedure in the rectal carcinoma depends on the characteristics of the tumour and the conditions of the patients, provided that the oncologic indications were respected, because recurrence and survival rate are independent from the surgical approaches.

Abdomen↗

A two-year longitudinal study of deferred imitation of object manipulation in a juvenile chimpanzee (Pan troglodytes) and orangutan (Pongo pygmaeus).

Changes in deferred imitation of novel actions on objects were assessed over a 2-year period in two enculturated, juvenile great apes (one chimpanzee, Pan troglodytes, and one orangutan, Pongo pygmaeus). Both apes displayed deferred imitation, and both displayed improve ments in deferred imitation over the 2-year period, although the magnitude of improvement was greater for the chimpanzee. This is, to our knowledge, the first experimental demonstration of longitudinal improvements of deferred imitation in great apes. The results were interpreted as reflecting maturationally paced cognitive differences consistent with other cognitive accomplishments in these species, and as demonstrating the influence that a species-atypical rearing environment can have on cognitive abilities in juvenile great apes.

Aging↗

Perikymata spacing and distribution on hominid anterior teeth.

We documented the spacing and distribution of perikymata on the buccal enamel surface of fossil hominin anterior teeth with reference to a sample of modern human and modern great ape teeth. A sample of 27 anterior teeth attributed to Australopithecus (5 to A. afarensis, 22 to A. africanus) and of 33 attributed to Paranthropus (6 to P. boisei, and 27 to P. robustus) were replicated and sputter-coated with gold to enable reflected light microscopy of their surface topography. Anterior teeth were then divided into 10 equal divisions of buccal crown height. The total perikymata count in each division of crown height was recorded using a binocular microscope fitted with a vernier micrometer eyepiece. Then the mean number of perikymata per millimeter was calculated for each division. Similar comparative data for a modern sample of 115 unworn human anterior teeth and 30 African great ape anterior teeth were collected from ground sections. Perikymata counts in each taxon (together with either known or presumed periodicities of perikymata) were then used to estimate enamel formation times in each division of crown height, for all anterior tooth types combined. The distributions of these estimates of time taken to form each division of crown height follow the same trends as the actual perikymata counts and differ between taxa in the same basic way. The distinction between modern African great apes and fossil hominins is particularly clear. Finally, we calculated crown formation times for each anterior tooth type by summing cuspal and lateral enamel formation times. Estimates of average crown formation times in australopiths are shorter than those calculated for both modern human and African great ape anterior teeth. The data presented here provide a better basis for exploring differences in perikymata spacing and distribution among fossil hominins, and provide the first opportunity to describe four specimens attributed to Homo in this context. Preliminary data indicate that differences may exist among the species attributed to early Homo, especially between Homo ergaster and Homo rudolfensis on the one hand, and Homo habilis sensu strico on the other.

Animals↗

Further evidence on relative dental maturation and somatic developmental rate in hominoids.

New data on hominoid dental development are presented. Individual bivariate pairings of all mandibular teeth were made for African apes and humans. Data were analyzed with a full linear regression model. No statistically significant differences were found among apes, although a consistent pattern of earlier incisal development was observed in Pan relative to Gorilla. This is concordant with an earlier fusion of the premaxillary:maxillary suture in Pan. Only one tooth pair differed significantly by sex among apes. Two biologically distinct human samples (Libben and Hamann-Todd), although assessed differently (extraction and radiography) yielded virtually identical results. Humans differ from apes only by earlier relative calcification of their anterior teeth. This can be viewed as a consequence of reduced facial prognathism and a shift in hominid canine function.

Animals↗

Heel contact as a function of substrate type and speed in primates.

In this report we provide detailed data on the patterns and frequency of heel contact with terrestrial and arboreal supports in primates. These data can help resolve the question of whether African apes and humans are uniquely "plantigrade" (Gebo [1992] Am. J. Phys. Anthropol. 89:29-58; Gebo [1993a] Am. J. Phys. Anthropol. 91:382-385; Gebo [1993b] Postcranial Adaptation in Nonhuman Primates), or if plantigrady is common in other primates (Meldrum [1993] Am. J. Phys. Anthropol. 91:379-381). Using biplanar and uniplanar videotapes, we recorded the frequency and timing of heel contact for a variety of primates (32 species) walking on the ground and on simulated arboreal supports at a range of natural speeds. Our results indicate that Pongo as well as the African apes exhibit a "heel-strike" at the end of swing phase. Ateles and Hylobates make heel contact on all supports shortly after mid-foot contact, although spider monkeys do so only at slow or moderate speeds. Data available from uniplanar videotapes suggest that this pattern occurs in Alouatta and Lagothrix as well. No other New or Old World monkey or prosimian in this study made heel contact during quadrupedalism on any substrate. Thus, heel contact occurs in all apes and atelines, but only the great apes exhibit a heel-strike. We suggest that heel contact with the substrate is a by-product of an active posterior weight-shift mechanism involving highly protracted hindlimbs at touchdown. Force plate studies indicate that this mechanism is most extreme in arboreally adapted primate quadrupeds walking on arboreal supports. Although heel contact and heel-strike may have no evolutionary link, it is possible that both patterns are the result of a similar weight shift mechanism. Therefore, the regular occurrence of heel contact in a variety of arboreal primates, and the absence of a true biomechanical link between limb elongation, heel contact, and terrestriality, calls into question the claim that hominid foot posture was necessarily derived from a quadrupedal terrestrial ancestor.

Animals↗

Looking for the lunate sulcus: a magnetic resonance imaging study in modern humans.

The position of the lunate sulcus in fossil endocasts (when it can be determined) may serve as a potential marker of cognitive development in extinct hominid species. While the lunate sulcus is reliably present in the brains of great apes and forms the anterolateral boundary of the primary visual cortex, in humans its presentation is much more variable, and even if present, it does not correspond to a functional region. Grafton Elliot Smith, who named the lunate sulcus, claimed that it was homologous in humans and the great apes. Using high-resolution MRI, we assessed the presence/absence and course of the lunate sulcus in 110 adult subjects. We found that in the vast majority of cases, lunate sulci identified on the surface of the occipital lobe are actually composed of smaller sulcal segments that converge into an apparently continuous composite lunate sulcus. We found only 3 examples in 220 hemispheres (1.4%) of continuous lunate sulci that resembled ape lunates in form (albeit in a more posterior position). Composite lunate sulci were found in 32.7% of left hemispheres and 26.4% of right hemispheres. These results, combined with those from histological and functional imaging studies, indicate that human and ape lunate sulci are not homologous structures. We suggest that the extent of functional reorganization of the occipital region during hominid evolution has been underestimated, and that changes in this region were not just passively shaped by expansion of parietal association cortex.

Adult↗

Broca's arrow: evolution, prediction, and language in the brain.

Brodmann's areas 44 and 45 in the human brain, also known as Broca's area, have long been associated with language functions, especially in the left hemisphere. However, the precise role Broca's area plays in human language has not been established with certainty. Broca's area has homologs in the great apes and in area F5 in monkeys, which suggests that its original function was not linguistic at all. In fact, great ape and hominid brains show very similar left-over-right asymmetries in Broca's area homologs as well as in other areas, such as homologs to Wernicke's area, that are normally associated with language in modern humans. Moreover, the so-called mirror neurons are located in Broca's area in great apes and area F5 in monkeys, which seem to provide a representation of cause and effect in a primate's environment, particularly its social environment. Humans appear to have these mirror neurons in Broca's area as well. Similarly, genetic evidence related to the FOXP2 gene implicates Broca's area in linguistic function and dysfunction, but the gene itself is a highly conserved developmental gene in vertebrates and is shared with only two or three differences between humans and great apes, five between humans and mice, and eight between humans and songbirds. Taking neurons and portions of the brain as discrete computational segments in the sense of constituting specific Turing machines, this evidence points to a predictive motor and conceptual function for Broca's area in primates, especially for social concepts. In human language, this is consistent with evidence from typological and cognitive linguistics.

Biological Evolution↗

Synthesis and muscarinic activity of a series of tertiary and quaternary N-substituted guvacine esters structurally related to arecoline and arecaidine propargyl ester.

A series of tertiary and quaternary N-substituted guvacine (1,2,5,6-tetrahydro-3-carboxy-pyridine) methyl and propargyl esters have been synthesized and tested for muscarinic/antimuscarinic activity on rat ileum and electrically paced left atria. Arecoline and arecaidine propargyl ester (APE) as well as their corresponding N-demethyl derivatives, guvacoline (norarecoline) and guvacine propargyl ester, acted as full agonists at both atrial and ileal muscarinic receptors (range of pD2-values 6.09-8.07). However, in both preparations arecoline and APE were clearly more potent (up to 15-fold) than their N-demethyl analogues. Replacement of the N-methyl group in arecoline and APE by larger substituents (ethyl, n-propyl, n-butyl, benzyl, phenylethyl) as well as N-methylation resulted in a decrease or even a complete loss of agonistic activity. In both organs, the propargyl esters usually showed higher potency than the corresponding methyl ester analogues. N-Ethylguvacine propargyl ester and APE methiodide displayed pronounced agonistic activity in the atria (pD2 approximately 6.5; intrinsic activity = 0.79 and 0.67, respectively) but behaved as competitive antagonists in the ileum (pA2 = 6.06 and 5.62, respectively). Beside the lower sensitivity to muscarinic agonists of the rat ileum as compared to rat atria, the cardioselective stimulant action of both agents may also be due to their ability to recognize structural differences between atrial M2 alpha and ileal M2 beta muscarinic receptor subtypes.

Animals↗

Early-stage rectal cancer: electrofulguration in comparison to abdominoperineal extirpation or low-anterior resection.

For some small rectal cancers electrofulguration can be an attractive alternative to more extensive surgical procedures. This report is a review of 49 patients who, after careful selection, were considered ideal candidates for curative fulguration in the period 1959-1982. All had rectal adenocarcinomas and were clinically staged as Dukes' A tumors. To put the results of this analysis into perspective, they are compared to the results of those patients (34) who also had early clinical stage rectal adenocarcinomas, but for a variety of reasons underwent abdominoperineal excisions (APE, 11 patients) or low-anterior resections (LAR, 23 patients) instead of fulguration. Postoperative complications after fulguration were minimal, there were no postoperative deaths, and all patients retained anal continence. After APE or LAR there were two postoperative deaths (one myocardial infarction, one ruptured iliac aneurysm); postoperative morbidity was greater. All LAR-treated patients remained continent. Of the patients at risk 55% remained disease-free after fulguration, while 77% remained disease-free after APE or LAR (P = 0.023). This is due to a higher percentage of loco-regional recurrences occurring after fulguration than after APE or LAR (31% vs 9%, respectively, P = 0.021). The percentage of patients with distant metastases in both groups are similar. It seems that electrofulguration of rectal cancers, even in strictly selected patients in a specialized institution, can lead to an unacceptably high percentage of patients with loco-regional recurrences. Nearly all local failures occurred in patients with tumors that measured more than 3 cm in diameter and/or occupied more than one-third of the rectal circumference. Salvage operations for loco-regional failure were performed in 13 patients, 5 of whom are alive with no evidence of disease. Since there seems to be a direct relation between tumor size and the chance of loco-regional recurrence and since salvage operations for local failure are not uniformly successful, electrofulguration for cure must be reserved for the very rare patient with a very small early-stage rectal cancer.

Adenocarcinoma↗

The phylogenetic affinities of Otavipithecus namibiensis.

The middle Miocene hominoid Otavipithecus namibiensis is the first and most complete fossil ape from sub-equatorial Africa and represents a significant addition to the taxonomically sparse African middle Miocene hominoid fossil record. The Otavipithecus hypodigm comprises the holotype mandible, which presents a unique mosaic of dental and gnathic characters, and several attributed cranial and postcranial elements which resemble the stem hominoid Proconsul. Contrary to initial hopes that this discovery would provide new insights into hominoid morphological diversity and phylogenetic relationships, a variety of conflicting phylogenetic hypotheses have been advanced suggesting ties to virtually every major large-bodied hominoid group (Conroy et al., 1992; Andrews, 1992 a; Conroy, 1994; Pickford et al., 1994; Begun, 1994 a). Cladistic analysis of a matrix of 22 qualitative and ten quantitative characters of the mandible and mandibular dentition found no support for a close phylogenetic relationship between Otavipithecus and either the African ape or great ape clades, or with any of the Eurasian fossil hominoids with which it has previously been compared. A close relationship between Otavipithecus and Kenyapithecus cannot be ruled out, but is deemed unlikely on the basis both of morphological comparisons and the absence of support within a cladistic framework. The present analysis indicates that Otavipithecus is most closely related to Afropithecus, as previously suggested by Andrews (1992 a) among others. Due to lack of statistical support for this result, a conservative interpretation, that these taxa represented related but divergent lineages of a late early Miocene hominoid radiation, is currently favored. Findings are consistent with the allocation of Otavipithecus to Andrews' (1992 a) tribe Afropithecini which represents the sister group to Kenyapithecus and the extant ape clade.

Africa↗

Innovative non-invasive method for absolute intracranial pressure measurement without calibration.

A new absolute ICP (aICP) measurement method was designed which does not need calibration. In this study we compared a new method with invasive aICP method in ICU on the patients with closed severe traumatic brain injury. A new method is based on two-depth TCD technique for aICP and external absolute pressure aPe comparison using the eye artery (EA) as natural "balance". The intracranial segment of EA is compressed by aICP and the extracranial segment is compressed by aPe applied to the tissues surrounding the eye. The blood flow parameters in both EA segments are approximately the same when aPe = aICP. Two-depth TCD device is used as an indicator of balance aPe = aICP when the pulsatility index of blood flow velocity waveform in intracranial and extracranial segments are the same. Fifty seven simultaneous invasive and non-invasive aICP measurements were performed in aICP range from 3.0 to 37.0 mmHg. Bland Altman plot of the differences between simultaneous invasive and non-invasive aICP measurements shows the negligible mean difference (mean = 0.94 mmHg) with a standard deviation of 6.18 mmHg. This validation study shows that it is possible to measure aICP non-invasively without calibration of the system with 95% confidence interval of 12 mmHg.

Adolescent↗

Local recurrence following abdominoperineal excision and anterior resection for rectal carcinoma.

The aim of this retrospective study is to compare the outcome of abdominoperineal excision (APE) and anterior resection (AR) for rectal cancer in terms of local tumor recurrence. A further comparison has been carried out between hand-sewn and stapled anastomosis; 147 patients have been followed for at least 2 years: 69 after APE and 78 after AR, 40 being stapled. The following variables potentially related to the risk of recurrence were evaluated: age, grading, staging, and site of the tumor. An overall 2-year local recurrence rate of 11 percent after APE and 12 percent after AR was observed, whereas it was 13 and 11 percent following stapled and hand-sewn sutures, respectively. Both differences were not statistically significant. A similar local recurrence rate was noted after APE and AR when the patients were matched for Dukes' stage and grading of the lesion. A trend toward an increased risk of recurrence following AR (P = 0.07) was shown when comparing the two procedures if mid and upper rectal cancers were grouped together. In the patients with anastomotic leaks after AR, no increase of local recurrence was observed. In conclusion, AR is unlikely to be followed by an increased risk of local recurrence and, therefore, when oncologically indicated, may be considered the operation of choice in the treatment of rectal cancer, although the possible risk of its overuse should be taken into account.

Abdomen↗

Assessment of threonine metabolism in vivo by gas chromatography/mass spectrometry and stable isotope infusion.

The fractional contributions (FC) of threonine to glycine and 2-ketobutyrate (KB) fluxes in fed pigs have been assessed by the constant infusion of L-[1-13C]-threonine. The analysis of the enantiomeric purity of labeled threonine by gas chromatography/mass spectrometric (GC/MS) analysis is reported as the N-TFA isopropyl ester derivative. The commercially available [1-13C]threonine comprised 98.7% of the L-enantiomer, enriched at 99 atom percentage excess (APE), and 1.3% of L-allo-threonine contaminant, also enriched at 99 APE. The enantiomeric purity of threonine in plasma of pigs infused for 10 h with [1-13C]threonine showed that the L-allo contaminant did not accumulate. The t-butyl dimethylsilyl derivatives of threonine, glycine, and 2-aminobutyrate (ABA) were used to measure the enrichment of these compounds in plasma and liver samples by GC/MS/selected ion monitoring analysis. Analyses were performed on between 1 and 5 nmol of each amino acid extracted from biological fluids and a 1:10 split injection. GC/MS parameters were assessed with standards at similar quantities and found to be satisfactory; e.g., injection of 1-10 nmol of glycine did not significantly alter the slope and the precision of the standard curve. The coefficient of variation of enrichment determination was less than 10% for standards enriched at 0.4 APE or more and biological samples enriched at 0.6 APE or greater. Within-animal coefficients of variation for four plasma samples obtained at equal intervals between 8 and 10 h of [1-13C]threonine infusion were 4, 21, and 24% for threonine, ABA, and glycine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗

Methoctramine, a cardioselective antagonist: muscarinic receptor mediating prostaglandin synthesis in isolated rabbit heart.

The antimuscarinic properties of the methoctramine with high selectivity for cardiac muscarinic M2 receptors were investigated on cholinergically induced changes in prostaglandin (PG) synthesis and mechanical function in the isolated perfused rabbit heart. Acetylcholine (ACh)- and arecaidine propargyl ester (APE)-induced increases in PG synthesis were significantly attenuated by methoctramine in a concentration-dependent manner. Methoctramine at a low concentration of 0.1 microM potentiated ACh-induced PG synthesis, which was blocked by simultaneous infusion of hexahydro-sila-difenidol (HHSiD), a M3 receptor antagonist. Methoctramine produced an additive effect with HHSiD in diminishing the ACh- or APE-induced PG synthesis. Methoctramine displayed a potent antagonistic activity at M2 receptors that mediate the decrease in heart rate and increase in coronary perfusion pressure in isolated perfused rabbit heart. Methoctramine also minimized ACh- and APE-induced decrease in developed tension. In contrast, at 0.1-0.75 microM it exhibited no antagonistic activity at vascular muscarinic receptors (M3) mediating vasodilation in response to ACh or APE. These data suggest that methoctramine has a high affinity for cardiac M2 receptors mediating increases in PG output and coronary perfusion pressure as well as decrease in heart rate and developed tension and has a low affinity for M3 receptors mediating coronary vasodilator response.

6-Ketoprostaglandin F1 alpha↗

Bacteremia-induced suppression of alveolar surfactant production.

Sepsis is characterized by Adult Respiratory Distress Syndrome (ARDS)-like pulmonary dysfunction largely attributed to alveolar capillary endothelial cell injury which causes increased microvascular permeability and interstitial edema formation. In addition, quantitative and qualitative abnormalities of the pulmonary surfactant system may be important features of some clinical and experimental lung injuries. This study was designed to investigate the relationship of bacteremia and endotoxemia to pulmonary surfactant production in vivo. A technique for estimation of pulmonary surfactant phospholipid synthesis measuring incorporation of a stable isotope precursor [( 2-13C]acetate) into dipalmitoylphosphatidylcholine (DPPC) in alveolar lavage fluid was developed. Male 350 g Sprague-Dawley rats had placement of central venous catheters. After overnight recovery, sublethal bacteremia (Escherichia coli, 1 x 10(8) organisms, iv) and sublethal endotoxemia (Difco; 10 mg/kg, iv) were induced. Both were associated with lung microvascular permeability increases consistent with capillary endothelial injury. Eight-hour infusions of [2-13C]acetate were given. After sacrifice, bronchoalveolar washings and lung tissue were obtained and [2-13C] incorporation into lavage and lung DPPC was measured by gas chromatography mass spectroscopy. Endotoxin-treated animals had a 21.5% reduction in label incorporation into DPPC [1.215 +/- 0.145 APE (%) sham versus 0.954 +/- 0.144 APE (%) experimental, P greater than 0.05] and bacteremic animals had a 56.9% diminution of [2-13C]acetate incorporation [1.215 +/- 0.145 APE (%) sham versus 0.524 +/- 0.56 APE (%) experimental, P less than 0.05]. Bacteremia-induced dysfunction of alveolar type II epithelial cells manifested as diminished alveolar surfactant phospholipid production may be a contributing factor to sepsis-induced respiratory failure.

1,2-Dipalmitoylphosphatidylcholine↗

Evolutionary implications of primate endogenous retroviruses.

Endogenous DNA sequences related to retroviruses are probably present in all primates. By using approaches based on the polymerase chain reaction, two separate studies have revealed the evolutionary history of some of these sequences. In the first study, a retrovirus-like reverse transcriptase (RT) sequence homologous to that of Baboon endogenous virus (BaEV) has been identified in both Old World monkeys and African apes, but not in humans or Asian apes. This RT sequence is highly conserved at the amino acid level, but not the nucleotide level, in the baboon, African green monkey, Java macaque, chimpanzee, and gorilla. The patterns of nucleotide substitution indicate functional conservation and suggest that this RT sequence was present in the primate germline before apes and Old World monkeys diverged about 30 million years ago. In the second study, a comparison of endogenous proviral DNAs and their adjacent sequences has been used to analyze the evolutionary history of three previously reported human endogenous retroviruses, HERV-E(4.14), HERV-R(3), and HERV-Ia. It is shown that these retroviruses have also been resident in the primate line since before the ape-Old World monkey divergence. The implications of the presence of functionally conserved RT genes in the germlines of primates, and the potential for using integration sites as tools for analyzing phylogenetic relationships among primates and their retroviruses, are discussed.

Amino Acid Sequence↗

Spondyloarthropathy as an Old World phenomenon.

The presence of spine and sacroiliac involvement and the nature and distribution of erosive lesions allowed definitive diagnosis of spondyloarthropathy in the great apes (Gorilla and Pan [chimpanzee]), the lesser ape (Hylobates), and Old World monkeys (Theropithecus, Papio, Cercopithecus, Macaca, Colobus, Presbytis, and Erythrocebus). Analysis of lesional character, distribution, radiological appearance, and sex ratios showed a picture indistinguishable from human spondyloarthropathy. This contrasts with orangutans (Pongo), who lack reactive bone or sacroiliac involvement. A different pathophysiology, as yet undefined, is implied for their erosive arthritis. Limited individual susceptibility to spondyloarthropathy in humans (1% to 4%), Old World monkeys (2.4%), and lesser apes (2.4%) contrasts with the high frequency of disease in the great apes (20% to 28%). The wide geographic distribution of this phenomenon suggests an African and perhaps Asian "panendemic." This natural disease state provides a unique model for in-depth analysis of the contribution of genetic and environmental factors to disease pathophysiology.

Animals↗

Differential expression of the apurinic / apyrimidinic endonuclease (APE/ref-1) multifunctional DNA base excision repair gene during fetal development and in adult rat brain and testis.

The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA binding capability of Jun-Jun homodimers and Fos-Jun heterodimers by altering their redox state and to be involved in calcium mediated transcriptional repression of the parathyroid hormone gene. Previous studies examining the tissue specific distribution of the AP endonuclease (APE) transcript and protein by Northern analysis and enzymatic assays, respectively, have shown that this gene is expressed in all tissues at relatively similar levels. In the current study, adult and fetal rat tissue sections were examined for the expression of the APE transcript in specific subpopulations of cells and during development by in situ hybridization. In the adult brain, the APE transcript showed a widespread, but heterogeneous pattern of expression. Predominant levels of transcript were detected in the suprachiasmatic nuclei, the supraoptic and paraventricular nuclei, the hippocampus and the cerebellum. During fetal development, transcript was detected in all somatic sites examined with very high levels in the thymus, liver and developing brain. Examination of the adult testis indicated that the expression of the transcript varies with the stage of spermatogenesis with the highest levels being present over round spermatids. These results provide evidence that the APE gene is not homogeneously expressed, but rather is found in subpopulations of cells in the brain and testes and during development.

Animals↗