Converse Smith-Martin cell cycle kinetics by transformed B lymphocytes.

Recent studies using direct live cell imaging have reported that individual B lymphocytes have correlated transit times between their G1 and S/G2/M phases. This finding is in contradiction with the influential model of Smith and Martin that assumed the bulk of the total cell cycle time variation arises in the G1 phase of the cell cycle with little contributed by the S/G2/M phase. Here we extend these studies to examine the relation between cell cycle phase lengths in two B lymphoma cell lines. We report that transformed B lymphoma cells undergo a short G1 period that displays little correlation with the time taken for the subsequent S/G2/M phase. Consequently, the bulk of the variation noted for total division times within a population is found in the S/G2/M phases and not the G1 phase. Models that reverse the expected source of variation and assume a single deterministic time in G1 followed by a lag + exponential distribution for S/G2/M fit the data well. These models can be improved further by adopting two sequential distributions or by using the stretched lognormal model developed for primary lymphocytes. We propose that shortening of G1 transit times and uncoupling from other cell cycle phases may be a hallmark of lymphocyte transformation that could serve as an observable phenotypic marker of cancer evolution.

Objective measurement of erythema in psoriasis using digital color photography with color calibration.

BACKGROUND: Traditional metrics for evaluating the severity of psoriasis are subjective, which complicates efforts to measure effective treatments in clinical trials. METHODS: We collected images of psoriasis plaques and calibrated the coloration of the images according to an included color card. Features were extracted from the images and used to train a linear discriminant analysis classifier with cross-validation to automatically classify the degree of erythema. The results were tested against numerical scores obtained by a panel of dermatologists using a standard rating system. RESULTS: Quantitative measures of erythema based on the digital color images showed good agreement with subjective assessment of erythema severity (κ = 0.4203). The color calibration process improved the agreement from κ = 0.2364 to κ = 0.4203. CONCLUSION: We propose a method for the objective measurement of the psoriasis severity parameter of erythema and show that the calibration process improved the results.

Three-dimensional assessment of treatment outcomes on the face.

OBJECTIVES: To investigate the effect on the face of treatment involving extractions. DESIGN: A prospective study of the effects of extraction and non-extraction treatment on two groups of patients was undertaken. SETTING AND SAMPLE POPULATION: Initially there were 16 non-extraction and 18 extraction patients but at the end of treatment there were only 12 in each group. EXPERIMENTAL VARIABLE: Each of the patients was scanned using a three-dimensional (3-D) MGI scanner and the 3-D scans were analysed using registration and surface shape analysis programs. The registration program registers the scans over the forehead and then shows the differences in colour between the two scans. The surface shape analysis mathematically differentiates the surface into nine different surface shapes. RESULTS: The results indicated that there was a difference between the two groups at the start of treatment but there were no differences in the effect on the face of treatment in the two groups. The surface morphology was similar at the end of treatment in both groups. CONCLUSION: It was concluded that in this preliminary study that whether treatment is undertaken with or without extractions, in this group of patients the facial morphology was not significantly different.

Three-dimensional assessment of the effects of extraction and nonextraction orthodontic treatment on the face.

The purpose of this prospective study was to compare the 3-dimensional (3-D) effects on the face of extraction and nonextraction orthodontic treatment in patients with skeletal Class I patterns. The sample of 24 patients included 12 whose treatment included extractions and 12 who were treated without extractions. Pretreatment study casts were assessed to evaluate dental differences between the 2 groups. Pretreatment and posttreatment lateral cephalograms and optical surface scans were also compared. In the lateral cephalometric assessment, the only significant (P <.05) pretreatment difference was lower lip length. Posttreatment, the nasolabial angle and lower lip thickness were significantly different (P <.05). Registration of the average 3-D optical surface scans indicated that, before treatment, the nonextraction group had longer and broader faces by 5 to 7 mm, and the upper lip and labiomental fold were 3 to 5 mm farther forward than in the extraction group. Posttreatment, the nonextraction group still had larger faces, but the difference was smaller. Faces in the extraction group became relatively more protrusive with treatment. The surface shape analysis technique showed that the cheeks were flatter in the nonextraction group at the start of treatment, but this reversed with time. In the extraction group, the concavity of the labiomental fold increased, while the nonextraction group showed no change in this area. The study demonstrates that 3-D optical surface scans offer more data for analysis compared with lateral cephalograms alone. It also highlights the changes that can be detected with surface shape analysis.

Facial growth: separating shape from size.

Optical surface scanning technologies produce dense three-dimensional (3D) data sets, which allow detailed analysis of surface morphology. This paper describes a method of analysing change in facial shape independently of change in size. The 3D data from three male subjects from the age of 6-21 years were recorded using an optical surface scanner. A series of 22 conventional landmarks were located with the aid of horizontal and vertical profiles across the face, and were analysed using geometric morphometrics. The 3D landmark co-ordinates were scaled and aligned using Generalized Procrustes Analysis (GPA) and analysed by Principal Component Analysis (PCA) to determine the shape change over the growth period for each individual. The results show that the centroid size reaches a steady value at different times for each of the subjects. When analysing shape versus age, highly significant correlations were found with principal component 1 (PC-1), but not with other principal components. PC-1 encompassed 40 per cent of the total variance for each subject. The movement of facial landmarks with time that is represented by PC-1 in each of the individuals is described. The use of these techniques has enabled the individual characteristics of facial growth to be identified and also has revealed the subtle changes in shape that continue after change in size has ceased.

An evaluation of the Faces Pain Scale with young children.

The psychometric characteristics of the Faces Pain Scale (FPS) were evaluated in three groups of preschool and school-aged children (3. 5-4.5; 4.5-5.5 and 5.5-6.5 years, respectively). The FPS was adequately comprehended by even young children. It was easily administered and was valid and discriminating. It did not, however, possess the linear scalability claimed by its authors.

Diaphyseal cross-sectional geometry of the Boxgrove 1 Middle Pleistocene human tibia.

Cross-sectional geometric analysis of the early Middle Pleistocene human tibia from Boxgrove, West Sussex, U.K. reveals a mosaic pattern relative to other archaic Homo tibiae. The specimen has relatively low percent cortical area within its cross sections. However, it exhibits the high mediolateral strength characteristic of archaic Homo tibiae. Scaled solely to tibial length it is robust, similar to those of the Neandertals and above those of early modern and pre-Late Pleistocene African and Asian humans. However, given ecogeographically-patterned variance in relative tibial length and body laterality, it is most likely that it exhibits a level of robusticity within the range encompassed by Late Pliocene to Late Pleistocene archaic Homo combined with arctic body proportions. Given its association with late interglacial cool temperate climatic indicators, the inferred body proportions of the Boxgrove hominid were probably promoted by their minimal level of cultural buffering, requiring a significant biological conservation of body heat.

The nature and development of nonverbal implicit memory.

The study investigated the course of developmental changes in performance on nonverbal implicit and explicit memory tests and examined the degree to which implicit memory performance is dependent upon the storage of specific perceptual information. Four-, 5-, and 10-year-old children were required to name fragmented pictures of common objects or to name and answer general knowledge questions about complete versions of the same pictures. After a 48-h retention interval, all subjects were presented with a fragmented picture identification task containing pictures identical to those present during encoding (old), pictures which were from the same basic category as the study items but which varied in their perceptual similarity to those items (same), and novel pictures which were visually and semantically unrelated to the study items (new). The amount of visual information needed to name each item (picture identification threshold) was recorded. Following identification, subjects were asked whether or not they had been shown the picture previously. All age groups showed significant priming such that the picture identification threshold for the old items was lower than that of the new pictures. A smaller but significant priming effect was obtained for the same-name items. This effect was maximized when the same-name items were perceptually similar to the study items. The magnitude of these priming effects did not vary as a function of age, but greater priming was found for those children who identified picture fragments during the study phase. In contrast, the sensitivity of recognition memory performance increased from 4 to 10 years of age. These results suggest that the processes that subserve pictorial repetition priming and recognition memory develop at different rates and that such priming is dependent upon access to specific perceptual representations of studied objects.

Somatostatin-containing D cells exhibit immunoreactivity for rat somatostatin cryptic peptide in six mammalian species. An electron-microscopical study.

Antisera raised against rat somatostatin cryptic peptide (RSCP; corresponding to amino acids 63-77 of rat pro-somatostatin), somatostatin-28-(1-12) and somatostatin-28-(17-28) were used to compare the morphological distribution of these pro-somatostatin-derived sequences within the gastroenteropancreatic system of six mammalian species, including man. Using the immunogold staining procedure, RSCP, SS28-(1-12) and SS28-(17-28) immunoreactivity was found to be present in all the D cells of the tissues investigated. Extra-islet RSCP and SS28-(1-12) immunoreactive cells were also identified in some species. RSCP, SS28-(1-12) and SS-28-(17-28) immunoreactivities were also present in a single case of human duodenal somatostatinoma. Immunostaining of serial ultrathin sections from all specimens in this study revealed that RSCP and both somatostatin immunoreactivities were co-localised in a majority of the reactive cells. Corroborative evidence was obtained by double immunogold staining which further showed that RSCP, SS28-(1-12) and SS28-(17-28) immunoreactivities were co-localised to individual secretory granules in D type cells, both normal and tumour. RSCP and SS28-(17-28) immunoreactivities were invariably co-localised, whereas SS28-(1-12) immunoreactivity was restricted to a sub-population of secretory granules. Our findings suggest that RSCP immunoreactivity is conserved in a number of mammalian species and is stored in each secretory granule type. Consequently, detection of the RSCP sequence may serve as a useful marker for somatostatin-producing systems throughout the diffuse neuroendocrine system.

Esthesioneuroblastoma: cerebral and spinal metastases without direct cranial invasion.

A patient with esthesioneuroblastoma is reported with metastatic lesions to the cervical nodes, intradural thoracic spinal canal, and the posterior fossa without evidence of local recurrence or cranial bone involvement four years after initial diagnosis and eradication. The initial lesion was a localized nasal polyp apparently treated adequately with excision and radiotherapy.

Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract.

Existing methods for the histochemical demonstration of gastrointestinal cells are somewhat limited. Chromogranin represents a family of proteins that coexist with catecholamines in the secretory vesicles of adrenal medulla cells. In the present study, immunocytochemistry was used to test whether chromogranin is a marker for gut endocrine cells. Serial sections of each area of human gut were immunostained for chromogranin and for the amine and each of the peptides known to be present in mucosal endocrine cells. Chromogranin was immunostained in large numbers of endocrine cells in all tissues examined. All identified endocrine cell types were found, in serial sections or by sequential silver impregnations, to be chromogranin immunoreactive. However, the possibility exists that some chromogranin-immunoreactive cells contain a yet to be discovered endocrine substance. Immunostaining of chromogranin thus appears to provide a means for demonstrating all gastrointestinal mucosal endocrine cells identifiable by the methods described in this study.

Investigation of immunogold-silver staining by electron microscopy.

Deposition of metallic silver on colloidal gold immunoreagents has been shown to be a very sensitive immunostaining technique capable of detecting low levels of immunoreactivity in tissue sections. Using electron microscopy we have shown that immunolabelling is highest with small sizes of gold which can penetrate sections better and achieve higher densities of particles in the section than larger particles. Chemical permeabilisation of the embedding medium aids the penetration of colloidal gold. The silver enhancement step in immunogold-silver staining was shown to be progressive, allowing optimisation of staining and the selection of the final size of silver deposits required. Some poorly understood features of the technique are rationalised and the additional knowledge gained will aid the wider application of this method.

Posterior-lateral foraminotomy as an exclusive operative technique for cervical radiculopathy: a review of 846 consecutively operated cases.

Between 1963 and 1980, one or more posterior-lateral foraminotomies were performed for simple cervical radiculopathy as the sole operative procedure for 736 patients. One hundred three patients (14%) required a second posterior procedure, but only 24 (3%) cases represented true recurrent radiculopathy. There were 13 minor complications (1.5%) and no deaths or detectable incidence of air embolism. All operations were done with the patient in the sitting position. Central venous pressure monitoring was used only infrequently. There was a 96% incidence of relief of significant arm pain and/or paresthesia and a 98% incidence of resolution of preoperatively present motor deficit. Eight hundred twenty-eight procedures (98%) were preceded by Pantopaque cervical myelography. There was a 71.5% incidence of correlation between preoperative clinical findings (both sensory and motor) and operative findings. In 13% of the cases, two spaces were thought by the operating surgeon to be equally involved by the spondylotic process. Most (91.5%) of the patients describe themselves as either "good or excellent" postoperatively. There was no significant difference postoperatively regarding results or recurrence between patients with suspected soft or hard disc protrusions and those with strictly spondylotic radiculopathy. Nor was there any statistical difference in results among the three patient population groups ("private" vs. compensation vs. liability). The mean length of time to return to work or other "normal" activities was 9.4 weeks. The mean length of follow-up time was 146 weeks (2.8 years). There was an associated incidence of significant lumbar disc and/or foraminal disease requiring operation of 33.4%.

Instrument myopia.

The basis for instrument myopia, the tendency to accommodate inappropriately while viewing through an optical instrument, was investigated in three experiments. The first demonstrated that the distance of a peripheral surround, analogous to a field stop, influences accommodation but that the magnitude of the effect cannot account for instrument myopia. The second experiment re-examined the hypothesis that perceived distance can affect accommodation. The data indicate that perceived distance is unlikely to influence accommodation and does not provide an explanation of instrument myopia. The last experiment tested the hypothesis that instrument myopia is a manifestation of the return of accommodation to an intermediate state of rest or equilibrium in the absence of an adequate stimulus for accommodation. Implications of the intermediate-resting-state hypothesis are discussed.