Search

Abstract: Background: Body composition analysis has been used to investigate fat mass (FM) and bone mineral content (BMC) in children and adolescents diagnosed with HIV. Investigating the validity of bioelectrical impedance analysis (BIA) is interesting with respect to testing useful techniques for monitoring body composition in children and adolescents in clinical practice. The present study aimed to determine the validity of body composition analysis by BIA compared to dual‐energy X‐ray absorptiometry (DXA) and air displacement plethysmography (ADP) in children and adolescents an HIV diagnosis. Methods: Sixty‐four children and adolescents (35 females and 29 males) with a mean (SD) age of 12.22 (2.13) years and with an HIV diagnosis participated in the study. Fat‐free mass (FFM), FM and body fat percentage (%BF) were obtained by BIA for comparison with DXA and ADP. Segmented FM (trunk, legs and arms), lean soft tissue mass (LSTM) (total and segmented) and BMC were obtained by BIA for comparison with DXA. Results: BIA presented a clinically acceptable correlation with DXA and ADP for FFM. Values found by BIA were underestimated compared to ADP, and overestimated compared to DXA. BIA presented a clinically acceptable correlation with DXA for LSTM estimates (total and segmented parameters) in both sexes (underestimating FM and overestimating LSTM). For other components (%BF, FM and BMC), BIA had a clinically unacceptable correlation with the reference methods in both sexes. Conclusions: BIA was suitable for evaluating FFM and LSTM in children and adolescents with an HIV diagnosis. For FM, %BF and BMC, BIA was not suitable for performing an evaluation in both sexes. [ABSTRACT FROM AUTHOR]

We present the palaeopathological analysis of a right fourth metatarsal (ATD6-124) recovered from the Atapuerca-Gran Dolina site (Spain). This fossil, ca. 1 Ma, belongs to Homo antecessor, the earliest known European hominin species. The metatarsal exhibits a proliferative lesion on its medial periosteal surface. Periosteal reaction can be the bone response to a wide number of injurious processes. We describe a lesion on the basis of macroscopic and microscopic analyses, including microtomography and scanning electron microscopy. Externally, the osteoblastic lesion presents a highly porotic and disorganised morphology. Internally, we observe a series of micro-fractures on the compact bone that do not affect the medullary canal. We provide a differential diagnosis and suggest that the ATD6-124 lesion could correspond to a pedal stress fracture, also known as fatigue or march fracture. Stress fractures have been related to a load increase and muscular fatigue. This type of fracture has been widely reported in the foot of soldiers and athletes, which are usually engaged in strenuous, excessive or prolonged locomotive activities. Despite its high frequency in these groups, stress fractures have not been reported as such in fossil collections, with the exception of a metatarsal belonging to the Sima de los Huesos site (Atapuerca). Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim Tumour regression grade (TRG) as defined by Rödel et al. has been used as an independent prognostic factor for rectal carcinoma after preoperative treatment by chemoradiotherapy (CRT). Determination of TRG 2 and 3, semiquantitatively defined as more or less than 50% tumour regression, respectively, does not appear to correlate with prognosis. The purpose of this study was to find an immunohistochemical pattern to permit improved stratification of intermediate responders defined by disease free (DFS) and overall survival (OS). Method Immunohistochemistry of EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), CD133 antibody, p53 antibody and Ki67 antibody was evaluated using tissue microarrays (TMA) on post-treatment surgical specimens from 88 patients. CD133 expression was confirmed in the whole section when available. Results At a median follow-up of 40 months, TRG was found to be an independent predictor of DFS ( P = 0.05) and OS ( P = 0.001) but no differences were found between TRG 2 and 3 in terms of DFS ( P = 0.74) or OS ( P = 0.41). The results of TMA showed an immunohistochemically poor prognostic profile for intermediate responders configured by negativity of CD133 expression. However, when examining CD133 expression in the whole section, there was an intermediate correlation with TMA and the prognostic significance was lost. Conclusion The results did not confirm the value of immunohistochemistry in predicting the prognosis of patients with rectal cancer following neoadjuvant chemoradiotherapy. This questions the accuracy of TMA in detecting CD133 expression in this setting. [ABSTRACT FROM AUTHOR]

We use a combination of rock magnetism (anisotropy of magnetic susceptibility, AMS) and magnetic polarity to characterize cave deposits and as a proxy for sedimentary fabric. In three localities at the Atapuerca archaeological site (Galeria, Gran Dolina and Sala de los Cíclopes), magnetic foliation (K max/K int) is always greater than lineation (K int/K min), consistent with a primary, depositional, sedimentary fabric. Our results, although preliminary, reveal a higher degree of anisotropy in autochtonous deposits compared to allochthonous deposits, possibly indicative of a higher hydrodynamic regime in the former. At two localities the magnetic lineation (K max) defines a cluster, which is thought to be antipodal to the palaeocurrent direction. Hence we are able to retrieve palaeoflow directions in deposits that otherwise lack any other sedimentary structure. We conclude that AMS is a powerful tool for determining the hydrodynamic character of depositional environments in cave sediments at the Atapuerca archaeological site. A better understanding of the depositional environment and how sedimentation occurred allows reconstruction of the karst evolution and ultimately a better definition of human interaction with the environment. [ABSTRACT FROM AUTHOR]

The association of human leukocyte antigen (HLA)-B27 to ankylosing spondylitis is one of the strongest between a major histocompatibility complex molecule and a disease. Yet, the basis for this association remains unknown. Several hypotheses, each based on a particular feature of HLA-B27, guide much of the current research on the pathogenesis of this disease, but none has yet satisfactorily explained its mechanism and the differential association of B27 subtypes to it. In this review, the pathogenetic role of HLA-B27 will be analyzed from a global perspective of its biology, emphasizing the interdependency of multiple molecular features and the likely influence of disease-modifying gene products. From this perspective, peptide binding emerges as the cornerstone of all other biological properties. [ABSTRACT FROM AUTHOR]

This study presents an analysis of linear enamel hypoplasias (LEH) and plane-form defects (PFD) in the hominine dental sample from the Sima de los Huesos (SH) Middle Pleistocene site in Atapuerca (Spain). The SH sample comprises 475 teeth, 467 permanent and 8 deciduous, belonging to a minimum of 28 individuals. The method for recording PFD and LEH is discussed, as well as the definition of LEH. The prevalence of LEH and PFD in SH permanent dentition (unilateral total count) is 4.6% (13/280). Only one deciduous tooth (lower dc) showed an enamel disruption. Prevalence by individual ranges from 18.7-30%. The most likely explanation for the relatively low LEH and PFD prevalence in the SH sample suggests that the SH population exhibited a low level of develop- mental stress. The age at occurrence of LEH and PFD was determined by counting the number of perikymata between each lesion and the cervix of the tooth. Assuming a periodicity of nine days for the incremental lines, the majority of LEH in the SH sample occurred during the third year of life and may be related to the metabolic stress associated with weaning. [ABSTRACT FROM AUTHOR]

The very strong association of human leukocyte antigen (HLA)-B27 with spondyloarthritis might be related to its peptide-presenting properties. The natural polymorphism of this molecule influences both peptide specificity and disease susceptibility. In this study, we present a comprehensive compilation of known natural ligands of HLA-B27 arising from endogenous proteins of human cells, together with a statistical assessment of residue usage among constitutive peptide repertoires of multiple HLA-B27 subtypes. This analysis provides evidence that every peptide position, including `non-anchor' ones, may be subjected to selection on the basis of its contribution to HLA-B27 binding and also allows a quantization of residue preferences at known anchor positions. The present registry is intended as a basis on which to build up reliable criteria to assess the effect of HLA-B27 polymorphism on peptide presentation, for T-cell epitope predictions, and for molecular mimicry studies. [ABSTRACT FROM AUTHOR]

The association of HLA-B27 with ankylosing spondylitis and other spondyloarthropathies ranks among the strongest between any HLA antigen and a human disease. Yet, in spite of intense research and advanced knowledge of the biochemistry and biology of major histocompatibility complex molecules, the mechanism of this association remains unknown. This review attempts a critical assessment of current pathogenetic hypotheses from evidence concerning the epidemiology of HLA–B27 association with disease, its peptide-binding specificity, and other aspects of the molecular biology and immunology of this molecule. [ABSTRACT FROM AUTHOR]

BACKGROUND In the last few decades, several studies have suggested a possible association between Stressful Life Events (SLEs) and the onset of Graves' Disease (GD). However, others have criticised this association and it has not yet been possible to prove it unequivocally. At present, we are not aware of studies correlating SLE and non autoimmune thyrotoxicosis. OBJECTIVE To assess possible associations between SLEs, the onset of GD and the onset of non autoimmune thyrotoxicosis (toxic nodular goitre, TNG). DESIGN A case–control retrospective study. PATIENTS This study included 93 subjects, divided into three groups of 31 each: GD, TNG and control (CG). The GD and TNG patients had thyroid disease diagnosed within the last 12 months, with clinical and biochemical confirmation. In the CG, psychopathological and endocrine disturbances had been ruled out. All three groups consisted of nine males (29%) and 22 females (71%). The mean age was 38·4 ± 10·9 years in the GD group, 48·3 ± 11·1 years in the TNG group and 41·1 ± 11·8 years in the CG group. SLEs were evaluated (number and impact) for the 12 months preceding the onset of symptoms of thyroid disease. MEASUREMENTS SLE occurrences and their impact on each group of cases were measured. To assess SLEs, we used the Life Experiences Survey (LES). Our statistical analysis included descriptive techniques and parametric and/or nonparametric comparative tests. P < 0·01 was considered statistically significant. Odds ratios were also calculated. RESULTS Patients with GD had a significantly greater number of SLEs compared to the TNG group and the CG (P < 0·001). The number and impact of negative SLEs were significantly higher in GD compared to TNG and CG (P < 0·001). The difference between TNG and CG was not significant (P > 0·01). GD had a higher impact of positive SLEs than TNG (P = 0·004), and no significant differences were found between the GD group and CG. Neutral SLEs were similar in the three groups. CONCLUSIONS These results suggest that SLEs are a precipitating factor of the onset of GD. We also demonstrated that SLEs do not seem to have any conclusive relationship with the onset of TNG. [ABSTRACT FROM AUTHOR]

17 patients allergic to thimerosal, with no previous history of photosensitivity or piroxicam ingestion, 2 patients with piroxicam-induced photosensitivity, and 10 controls were patch or photopatch tested, with 1 or more of the following: thimerosal, thiosaheylic acid, irradiated and non-irradiated solutions or piroxicam alone. L-cysteine alone and piroxicam plus L-cysteine, and piroxicam in petrolatum. The results of the tests supported the hypothesis that there are cross-reactions between thiosalicylic acid and piroxicam, a photosensitizer The mechanism of the cross-reactions may involve photoproducts of piroxicam and L-cysteine, as patients allergic to thiosalicylic acid, who have positive photo-patch tests to piroxicam, also had positive patch tests to the irradiated solution of piroxicam plus L-cysteine. [ABSTRACT FROM AUTHOR]

A patient with persistent photosensitivity and positive photopatch tests to musk ambrette and an after-shave lotion is reported. Phototests showed extreme sensitivity to UV radiation, especially UVB. Patch tests with the European Standard Series and some plant allergens were negative. Histology showed a granulomatous reaction with epithelioid and giant cells in the dermis. [ABSTRACT FROM AUTHOR]

Abstract The two most frequent HLA-B27 subtypes worldwide are B*2704 and B*2705. In the Han population of China B*2704 and, to a lower extent, B*2705 are found with significant frequency, and both are associated to ankylosing spondylitis (AS). Two articles in this issue report that the association to AS in this ethnic group is stronger for B*2704 than for B*2705. Thus, at least among the Han, B*2704 would be the strongest known susceptibility factor for AS. [ABSTRACT FROM AUTHOR]

1 The introduction of morphine antagonists into anaesthesiology has aroused great scientific interest, increased our knowledge of analgesia, and opened new frontiers for therapeutics. 2 The advantages and disadvantages of these compounds are described and assessed. 3 The best choices for treatment of pain are the most potent and long-acting drugs of this group with a wide safety margin. As an antidote to narcotic agonists, naloxone seems to be the most suitable drug in the majority of cases, although in certain conditions drugs having less rapid onset of action and of longer duration may be more desirable. 4 In all cases of treatment after anaesthesia when antagonists to narcotic analgesics are used, drug administration must depend on careful control, which necessitates specific and prolonged patient care by specifically trained and competent staff. [ABSTRACT FROM AUTHOR]

Studies the prevalence of type 1 diabetes mellitus in Portugal during the years 1995-1999 by a cohort study of young Portuguese men. Study of database belonging to the Portuguese Army's Recruitment Directorate related to type 1 diabetes diagnosis and other information; Regional variation in the prevalence of diabetes; Average age of the diabetics and increase in prevalence of the disease; Confirmation of an increase in type 1 diabetes in Portugal from 1995 to 1999.

This article reports on photoallergy caused due to musk ambrette. Musk ambrette is a synthetic nitromusk compound, which is largely used in perfumery, cosmetics, toiletries. topical medications, detergents and even in food. Contact and photocontact allergy to this substance have increased in recent years. During 1982. 7 male patients with photoallergy to musk ambrette were observed. Clinical picture for all of them is same. All of them developed erythema, squamous and pruriginous dermatitis in the beard region. On patch testing it was found that they were allergic to perfumed products. Therefore, it was suggested that shaving cream or after shave lotions could be the causitive agents of allergy.

BACKGROUND In the last few decades, several studies have suggested a possible association between Stressful Life Events (SLEs) and the onset of Graves' Disease (GD). However, others have criticised this association and it has not yet been possible to prove it unequivocally. At present, we are not aware of studies correlating SLE and non autoimmune thyrotoxicosis. OBJECTIVE To assess possible associations between SLEs, the onset of GD and the onset of non autoimmune thyrotoxicosis (toxic nodular goitre, TNG). DESIGN A case–control retrospective study. PATIENTS This study included 93 subjects, divided into three groups of 31 each: GD, TNG and control (CG). The GD and TNG patients had thyroid disease diagnosed within the last 12 months, with clinical and biochemical confirmation. In the CG, psychopathological and endocrine disturbances had been ruled out. All three groups consisted of nine males (29%) and 22 females (71%). The mean age was 38·4 ± 10·9 years in the GD group, 48·3 ± 11·1 years in the TNG group and 41·1 ± 11·8 years in the CG group. SLEs were evaluated (number and impact) for the 12 months preceding the onset of symptoms of thyroid disease. MEASUREMENTS SLE occurrences and their impact on each group of cases were measured. To assess SLEs, we used the Life Experiences Survey (LES). Our statistical analysis included descriptive techniques and parametric and/or nonparametric comparative tests. P < 0·01 was considered statistically significant. Odds ratios were also calculated. RESULTS Patients with GD had a significantly greater number of SLEs compared to the TNG group and the CG (P < 0·001). The number and impact of negative SLEs were significantly higher in GD compared to TNG and CG (P < 0·001). The difference between TNG and CG was not significant (P > 0·01). GD had a higher impact of positive SLEs than TNG (P = 0·004), and no significant differences were found between the GD group and CG. Neutral SLEs were similar in the three groups. CONCLUSIONS These results suggest that SLEs are a precipitating factor of the onset of GD. We also demonstrated that SLEs do not seem to have any conclusive relationship with the onset of TNG. [ABSTRACT FROM AUTHOR]

The aim of this study is to describe the morphology of the roots and root canals of permanent lower second premolars (LP4s) with fully developed roots of five hominin groups: Homo sp. (ATE9-1 specimen) from Atapuerca-Sima del Elefante locality, H. antecessor (ATD6-4 and ATD6-125) from Atapuerca-Gran Dolina TD6 locality, H. heidelbergensis from Atapuerca-Sima de los Huesos locality, H. neanderthalensis from Krapina, Regourdou, and Abri Bourgeois-Delaunay localities, and two contemporary H. sapiens groups. The teeth were scanned by means of microtomography. The roots were divided into three virtual segments by three planes: cemento-enamel junction (CEJ), mid-root (MR), and mid-apex (MA). Volumetric and planar direct measurements of the whole teeth and each segment were taken. Descriptive statistical analyses and nonparametric Mann-Whiney test were performed to test for significant differences (P < 0.025) between groups. ATE9-1 and Gran Dolina-TD6 fossils present intricate radicular complexes that might be transitional between the morphologies of Australopithecus robustus and African early Homo and the derived conditions typically found in later Homo. In H. neanderthalensis and H. heidelbergensis, the root canals are wide, with small apical convergence. This trait is particularly pronounced in the Sima de los Huesos sample which may reflect a particularity of this population. Our study demonstrates the potential of hominin roots and root canals as untapped sources of taxonomic information when the tooth crown is fragmented. Future studies, including more fossil specimens and species will shed light in the polarity of the morphologies observed., (Copyright © 2012 Wiley Periodicals, Inc.)

1. Recently, we demonstrated that oral captopril treatment improved diastolic function and attenuated cardiac remodelling after myocardial infarction (MI) in rats. Considering the feasible role of the brain renin-angiotensin system (RAS) in heart failure, in the present study we investigated the role of the captopril injected intracerebroventricularly (i.c.v.) on the progression of cardiac dysfunction. 2. Male Wistar rats underwent experimental MI or sham operation. Infarcted animals received daily i.c.v. injections of captopril (approximately 200 mg/kg; MI + Cap) or saline (MI) from 11 to 18 days after infarction. Electro- and echocardiogram assessments were performed before and after i.c.v. treatment (10 and 18 days after MI, respectively). Water and hypertonic saline ingestion were determined daily between 12 and 16 days after MI. 3. Electrocardiograms from the MI and MI + Cap groups showed signs that resembled large MI before and after i.c.v. treatment. However, despite similar systolic dysfunction observed in both groups, only captopril-treated rats exhibited reduced left ventricular (LV) dilatation and improved LV filling, as assessed by echocardiograms, and low levels of water ingestion compared with the saline-treated control group. 4. The results of the present study suggest that the brain RAS may participate in the development of cardiac dysfunction induced by ischaemia and that inhibition of the brain RAS may provide a new strategy for the prevention of diastolic dysfunction.

Objective: To characterize putative changes in the HLA-B27-bound peptide repertoire following infection of lymphoid cells with Salmonella typhimurium, a bacterium known to trigger reactive arthritis in HLA-B27-positive individuals., Methods: A protocol was developed for efficient large-scale infection of lymphoblastoid cell transfectants expressing HLA-B*2705. HLA-B27-bound peptide pools were isolated from noninfected and infected B*2705+ cells and comparatively analyzed by high-performance liquid chromatography. Peptide-containing chromatographic fractions from noninfected and infected cells were systematically compared by mass spectrometry (MS) to look for putative differences at the level of individual peptides., Results: The presence of B*2705 did not influence S typhimurium invasion, since this was equally efficient in nontransfected or B27-transfected cells. The chromatographic profiles of B*2705-bound peptides from noninfected and infected cells were virtually identical. A total of 808 molecular species were compared by MS. Of these, 807 were present in both infected and noninfected cells. Only one molecular species from infected cells lacked a detectable counterpart in noninfected cells., Conclusion: Intracellular infection of lymphoid cells by S typhimurium induces minimal alterations in the HLA-B27-bound peptide repertoire. Minor changes detectable by cytotoxic T lymphocytes, but not easily amenable to direct biochemical analysis, are not ruled out.

. We describe the pattern of dental development of Hominid XVIII from the Middle Pleistocene Sima de los Huesos (SH) site of the Sierra de Atapuerca (Burgos, Spain). As expected, this pattern is similar to that of modern humans. A delay of development of the lower and upper canines was observed. In contrast, the relative advanced development of the lower second molars and, especially, the upper and lower third molars is noteworthy. This latter feature seems to be common in Pleistocene hominids, and suggests that the pattern of dental development evolved in the genus Homo during the Pleistocene. In European Middle Pleistocene hominids, this pattern probably was facilitated by the extra space available in the mandible and maxilla for developing teeth., (Copyright 2001 Wiley-Liss, Inc.)

Objective: To investigate the rules governing peptide binding to HLA-B*2705, and to B*2704 and B*2706, which are 2 subtypes differentially associated with ankylosing spondylitis., Methods: Poly-Ala analogs carrying the HLA-B27 motif Arg-2, and substitutions at anchor positions P1, P3, or Pomega, were used to determine a binding score for each residue at each position. Binding was assessed in a quantitative epitope stabilization assay, where the cell surface expression of HLA-B27 was measured by flow cytometry as a function of peptide concentration., Results: Peptide anchor residues contributed additively to B*2705 binding. About 15% of the natural B*2705 ligands used a deficient P3 or Pomega anchor, but never both, indicating that detrimental anchoring at one of these positions is always compensated by a good anchor at the other one. About 50% of the B*2705 ligands used suboptimal P1 residues. However, this was compensated with optimal P3 and/or Pomega anchoring. Peptides that were longer than decamers used good anchor residues at the 3 positions, suggesting more stringent binding requirements. B*2704 and B*2706 differed in their residue specificity at P1, P3, and Pomega. The rules derived for B*2705 also applied to the known ligands of these 2 subtypes., Conclusion: The B*2705, B*2704, and B*2706 peptide repertoires are limited by the allowed residue combinations described in this study. The differential association of B*2704 and B*2706 with spondylarthropathy correlates with differences in their peptide specificity at multiple anchor positions. However, it is now possible to predict the peptide features that determine this differential binding to both subtypes.

Casts of nonocclusal enamel surfaces of 190 teeth from the Middle Pleistocene site of Sima de los Huesos have been micrographed by scanning electron microscopy. Microscopic analyses of striation density and length by orientation show distinct patterns of intrapopulation variability. Significant differences in the number and length of the striations by orientation are found between maxillary and mandibular teeth. This probably reflects differences in the mechanical forces involved in the process of chewing food. Significant differences are present between isolated and in situ teeth that could be caused by postdepositional processes differentially affecting the isolated teeth. In addition, a distinct and very unusual striation pattern is observed in a sample of teeth that can be explained only by a strong nondietary, most probably postmortem abrasion of the enamel surfaces. These teeth have a very high density of scratches, shorter in length than those found on other teeth, that are not indicative of dietary habits. No known depositional process may account for the presence of such postmortem wear since heavy transportation of materials within the clayish sediments has been discarded for the site. Despite this, a characteristic dietary striation pattern can be observed in most of the teeth analyzed. Most likely the diet of the Homo heidelbergensis hominids from Sima de los Huesos was highly abrasive, probably with a large dependence on hard, poorly processed plant foods, such as roots, stems, and seeds. A highly significant sex-related difference in the striation pattern can also be observed in the teeth analyzed, suggesting a differential consistency in the foods eaten by females and males.

The recent discovery of unexpectedly ancient human remains has fuelled interest about the first dispersion of Homo outside Africa. The Dmanisi mandible is perhaps one of the most interesting findings, as it supposedly represents one of the oldest hominids outside of Africa. Recently, different interpretations have been published about this specimen. Our comparison of the Dmanisi mandible with a large sample of mandibles and teeth has led us to a new interpretation. In our view, the Dmanisi mandible exhibits a unique combination of traits. Some of its features, taken in isolation, may be attributed to morphological extremes within the genus Homo. The architecture of the mandible as well as the morphology and dimensions of incisors, canines, and P3s are clearly primitive. However, dental traits such as the reduction of the talonid in the P4s and a distally decreasing molar series seems to be derived. Some combinations of these traits are found in specimens of Homo ergaster and differ from those generally present in later hominids. Thus, we propose that the Dmanisi mandible might be taxonomically classified as Homo sp. indet. (aff. ergaster). Furthermore, some aspects of the dentition in Dmanisi display close similarities to Asian Homo erectus. If the 1.8-1.6 Myr dating for the Dmanisi mandible is correct, the differentiation of the Asian branch of the genus Homo could be regarded as a very ancient event.

The dental sample recovered from the Sima de los Huesos (SH) Middle Pleistocene cave site of the Sierra de Atapuerca (Spain) includes 296 specimens. Interproximal wear grooves have been observed in 20 maxillary and mandibular posterior teeth belonging to at least five of the 32 individuals identified so far in the SH hypodigm. Interproximal grooving affected only the adults, and at an age between 25 and 40 years. The appearance, morphology, and location pattern of the SH wear grooves are similar to those reported in other fossil hominids and in more recent human populations. Two alternative proposals, the toothpicking and the fiber or sinew processing hypotheses, compete for explaining the formation of this anomalous wear. The characteristics observed in the wear grooves of the SH teeth are compatible only with the habitual probing of interdental spaces by means of hard and inflexible objects. Dietary grit may also have contributed to the abrasion of the root walls during the motion of the dental probes.

In order to reassess previous hypotheses concerning dental size reduction of the posterior teeth during Pleistocene human evolution, current fossil dental evidence is examined. This evidence includes the large sample of hominid teeth found in recent excavations (1984-1993) in the Sima de los Huesos Middle Pleistocene cave site of the Sierra de Atapuerca (Burgos, Spain). The lower fourth premolars and molars of the Atapuerca hominids, probably older than 300 Kyr, have dimensions similar to those of modern humans. Further, these hominids share the derived state of other features of the posterior teeth with modern humans, such as a similar relative molar size and frequent absence of the hypoconulid, thus suggesting a possible case of parallelism. We believe that dietary changes allowed size reduction of the posterior teeth during the Middle Pleistocene, and the present evidence suggests that the selective pressures that operated on the size variability of these teeth were less restrictive than what is assumed by previous models of dental reduction. Thus, the causal relationship between tooth size decrease and changes in food-preparation techniques during the Pleistocene should be reconsidered. Moreover, the present evidence indicates that the differential reduction of the molars cannot be explained in terms of restriction of available growth space. The molar crown area measurements of a modern human sample were also investigated. The results of this study, as well as previous similar analyses, suggest that a decrease of the rate of cell proliferation, which affected the later-forming crown regions to a greater extent, may be the biological process responsible for the general and differential dental size reduction that occurred during human evolution.

The prevalence and chronology of enamel hypoplasias were studied in a hominid dental sample from the Sima de los Huesos (SH) Middle Pleistocene site at the Sierra de Atapuerca (Burgos, northern Spain). A total of 89 permanent maxillary teeth, 143 permanent mandibular teeth, and one deciduous lower canine, belonging to a minimum of 29 individuals, were examined. Excluding the antimeres (16 maxillary and 37 mandibular cases) from the sample, the prevalence of hypoplasias in the permanent dentition is 12.8% (23/179), whereas the deciduous tooth also showed an enamel defect. No statistically significant differences were found between both arcades and between the anterior and postcanine teeth for the prevalence of hypoplasias. In both the maxilla and the mandible the highest frequency of enamel hypoplasias was recorded in the canines. Only one tooth (a permanent upper canine) showed two different enamel defects, and most of the hypoplasias were expressed as faint linear horizontal defects. Taking into account the limitations that the incompleteness of virtually all permanent dentitions imposes, we have estimated that the frequency by individual in the SH hominid sample was not greater than 40%. Most of the hypoplasias occurred between birth and 7 years (N = 18, X = 3.5, SD = 1.3). Both the prevalence and severity of the hypoplasias of the SH hominid sample are significantly less than those of a large Neandertal sample. Furthermore, prehistoric hunter-gatherers and historic agricultural and industrial populations exhibit a prevalence of hypoplasias generally higher than that of the SH hominids. Implications for the survival strategies and life quality of the SH hominids are also discussed.

We describe a method for electron microscopy that combines myeloperoxidase or acid phosphatase cytochemistry with the labelling of cell surface antigens with monoclonal antibodies and colloidal gold. This technique was tested in samples of normal mononuclear cells, leukaemic T cells with a mature or immature phenotype and an acute myeloid leukaemia. This method allows the demonstration at a single cell level of ultrastructural morphology, cytochemical reaction and the presence of a membrane antigen. It will improve further the analytic power of electron microscopy in the characterization of leukaemic cells particularly in cases of mixed leukaemias and in the study of normal haemopoietic differentiation with monoclonal antibodies.

The occurrence of third molar agenesis was recorded in a sample of 1,492 maxillary and 1,718 mandibular arches belonging to the prehistoric settlers of the Gan Canaria, Tenerife, and La Gomera Islands (Canary Islands). There were significant sex differences only in the Tenerife sample for the maxilla, the incidence in females being higher than in males. In the Gran Canaria sample, the total frequency (male and female combined) of third molar agenesis (individual count method) was 8.7% for the maxilla and 9.3% for the mandible. In the Tenerife and La Gomera samples, the frequencies were 11.1% and 10.7% for the maxilla and 14.6% and 13.3% for the mandible. In the Tenerife sample, the differences between both jaws were statistically significant. The incidence of missing third molars in the mandible was significantly higher in Tenerife than in Gran Canaria, but the other sample differences were statistically nonsignificant. Bilateral absence of third molars was observed in about two-thirds of the specimens examined. Some correlation between both jaws for the occurrence of third molar agenesis was found. The hypotheses that have been proposed in order to explain third molar agenesis in man are discussed. It is suggested that the loss of the third molar in Homo sapiens could be produced by a heterochronic phenomenon of postdisplacement, as a consequence of the phylogenetic tendency toward the delay of the onset of the third molar formation, and that the genetic factors responsible for the absence of these teeth could be related to the general process of delay in tooth formation.

A panel of 19 monoclonal antibodies (McAb) and the enzyme terminal transferase (TdT) have been applied to the characterization of poorly differentiated blasts from 50 patients with chronic granulocytic leukaemia (CGL) and myelofibrosis in blast crisis (BC), acute myelofibrosis and undifferentiated leukaemia. These cells were also extensively studied by transmission electron microscopy (TEM) (see Polli et al, 1985a). McAb against platelet glycoproteins (GP) showed a high specificity for megakaryoblasts, in particular those reactive with the GPIIb/IIIa complex (J15) and GPIIIa (C15 and C17), which were positive in a higher proportion of blasts than the McAb to GPIb (AN51 and FMC25). Findings with these anti-platelet McAb paralleled those of the platelet-peroxidase (PPO) reaction in 76% of cases studied simultaneously. The PPO reaction was always positive in cases in which two or more of the McAb were reactive with the blast cells. The differences observed suggest, nevertheless, that PPO is more sensitive for megakaryoblasts than the McAb and that this TEM technique should be reserved for cases which are negative with the platelet specific McAb. Of the McAb against myeloid antigens used in this series OKM1 was positive in 50% of cases but the others failed to demonstrate early features of differentiation in myeloblasts and monoblasts. In only three cases were erythroid precursors demonstrated by TEM and these were the only ones reactive with a McAb to glycophorin-A (LICR LON/R10). TdT and the McAb J5 helped in the identification of lymphoblasts which were seen as a 'pure' proliferation in 23% of CGL-BC and as part of blast cell mixtures in another 17% of cases. The McAb reactive to haemopoietic precursor cells (RFB1, FMC8 and OKIa), on the other hand, were of no practical value for the classification of blast cell types. The lineage specificity of several of the McAb used in this study, confirmed by TEM, suggest that these reagents are valuable tools for the characterization of immature blast cells.

A systematic analysis of the blast cell population was carried out on samples from 50 patients suffering from blast transformation of chronic granulocytic leukaemia (CGL) (31) and of myelofibrosis (4), acute myelofibrosis (AM) (11) and undifferentiated acute leukaemia (4). Transmission electron microscopy (TEM), used in 41 samples, included: morphology and techniques for myeloperoxidase (MPO), platelet-peroxidase (PPO) and acid phosphatase (AP). The majority of cases were also studied by light microscopy cytochemistry and with a battery of cell markers which are reported in the accompanying paper (San Miguel et al, 1985). The characterization of the type(s) of proliferating blasts was made from the integration of ultrastructural and immunological data. TEM morphology allowed the precise recognition of specific granules in basophil and mast-cell precursors and of ferritin particles in blasts of erythroid lineage; these rare cell types were not adequately characterized by other methods. The PPO reaction made possible the identification of pure megakaryoblastic proliferations in 38% of cases, including eight of the 11 with AM; megakaryoblasts were also present in nine of 12 cases with mixed blast cell types. The MPO and AP reactions were useful for the characterization of myeloblasts and monoblasts, respectively. Lymphoblasts could be distinguished from other cell types by TEM morphology and negative MPO and PPO reactions. TEM techniques were valuable for diagnosing correctly the type of blast cell in this study in which only four cases (8%) remained unclassifiable.