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Assessing the clinical probability of pulmonary embolism.

Clinical assessment is a cornerstone of the recently validated diagnostic strategies for pulmonary embolism (PE). Although the diagnostic yield of individual symptoms, signs, and common laboratory tests is limited, the combination of these variables, either by empirical assessment or by a prediction rule, can be used to express a clinical probability of PE. The latter may serve as pretest probability to predict the probability of PE after further objective testing (posterior or post-test probability). Over the last few years, attempts have been made to develop structured prediction models for PE. In a Canadian multicenter prospective study, the clinical probability of PE was rated as low, intermediate, or high according to a model which included assessment of presenting symptoms and signs, risk factors, and presence or absence of an alternative diagnosis at least as likely as PE. The prevalence of PE in the low, intermediate, and high pretest probability categories was 3, 28, and 78%, respectively. This model relies heavily on the clinician's subjective judgement as to whether an alternative diagnosis is as likely as or more likely than PE, and, as such, it can be hardly standardized. Furthermore, the inherent complexity of the model may limit its applicability in daily clinical practice. Recently, a simple clinical score was developed to stratify outpatients with suspected PE into groups with low, intermediate, or high clinical probability. Logistic regression was used to predict parameters associated with PE. A score =/<4 identified patients with low probability of whom 10% had PE. The prevalence of PE in patients with intermediate (score 5-8) and high probability (score > or = 9) was 38 and 81%, respectively. As opposed to the Canadian model, this clinical score is standardized. The predictor variables identified in the model, however, were derived from a data base of emergency ward patients. This model may, therefore, not be valid in assessing the clinical probability of PE in inpatients. In the PISA-PED study, a clinical diagnostic algorithm was developed which rests on the identification of three relevant clinical symptoms and on their association with electrocardiographic and/or radiographic abnormalities specific for PE. Among patients who, according to the model, had been rated as having a high clinical probability, the prevalence of proven PE was 97%, while it was 3% in those with low probability. The prevalence of PE in patients with intermediate clinical probability was 41%. These results underscore the importance of incorporating the standardized reading of the electrocardiogram and of the chest radiograph into the clinical evaluation of patients with suspected PE. The interpretation of these laboratory data, however, requires experience. Future research is needed to develop standardized models, of varying degree of complexity, which may find application in different clinical settings to predict the probability of PE.

Algorithms↗

Comparative anatomy of melanin pigment in the stria vascularis. Evidence for a distinction between melanocytes and intermediate cells in the cat.

Although Corti in 1851 first described the presence of cochlear pigmentation in the stria vascularis (SV) of "very old" cats, modern studies have failed to find pigment consistently in the feline stria. While the variable presence of pigment in the feline SV would appear to contrast with this structure's uniform pigmentation in other mammalian species, variability in both the distribution and abundance of inner ear pigment has rarely been studied in any species. In the present study, the SV was examined light microscopically in sectioned material or whole-mounts from pigmented and albino animals of 5 species, including the cat, guinea pig, rabbit, ferret and mouse. In these species, the SV of each pigmented animal contained varying amounts of melanin pigment and none was found in the albino inner ear. Pigmented guinea pigs contained the most uniformly dense and least variable distribution of strial melanin, followed by the rabbit, mouse, ferret and cat. Several species also displayed more strial pigment apically and less basally. In cats, pigmented cells were principally located adjacent to the strial capillaries. Ultrastructural studies of the stria in pigmented cats revealed that these perivascular cells frequently contained an abundance of pigmented organelles and other structural features which allowed them to be distinguished from intermediate cells.

Animals↗

Density-dependent outcomes in a digestive mutualism between carnivorous Roridula plants and their associated hemipterans.

Recent studies have shown that mutualisms often have variable outcomes in space and time. In particular, the outcomes may be dependent on the density of the partners with unimodal or saturating outcomes providing stability to the mutualism. We examine density-dependent outcomes of an obligate, species-specific mutualism between a South African carnivorous plant (Roridula dentata) and a hemipteran (Pameridea) that facilitates prey digestion, but also sucks plant sap. Plants occur in sandy, leached, nitrogen-poor soils and have no digestive enzymes to digest prey. Instead they rely on obligately dependent hemipterans to supply nitrogen by digesting prey for them and defecating on their leaves. We documented the densities of Pameridea on Roridula in the field. In the greenhouse, we manipulated the hemipteran densities on Roridula and measured the mean relative growth rates of plants with differing hemipteran densities. Plants exhibited a unimodal response to the density of their mutualist partners. Those with no hemipterans had negative growth rates, suggesting that hemipterans are important in facilitating nitrogen absorption. Plants with intermediate hemipteran densities had positive growth rates but growth rates were negative under very high hemipteran densities. Our research provides support for variable and unimodal outcomes in mutualism. Unimodal outcomes may be particularly important in obligate mutualisms and this is one of the few studied outside of pollinating seed parasite mutualisms. In this system, extrinsic factors such as other predators may affect the mutualism by altering the numbers of hemipterans.

Animals↗

Stress-coping factors in adolescent substance use: test of ethnic and gender differences in samples of urban adolescents.

Investigated group differences in the relationship between stress-coping variables and substance (cigarette, alcohol, and marijuana) use with samples of inner-city students in sixth through eighth grades (N = 1,289) and metropolitan-area students in seventh through ninth grades (N = 1,702). Measures included affect, life events, parental support, and coping patterns. African-American adolescents had the lowest rate of substance use, Hispanics were intermediate, and Whites had the highest rate; there was no gender difference in overall substance use. Multiple regression analysis showed the strength of predictive relationships for stress-coping variables was lower for African Americans and was greatest for Whites; four methodological tests showed these differences were not attributable to statistical artifacts. Hispanic adolescents showed greater vulnerability than Whites at younger ages but this effect reversed at later ages. Implications for prevention research are discussed.

Adaptation, Psychological↗

Human malignant mesothelial cells: variability of ultrastructural features in established and nude mice transplanted cell lines.

The aim of this study was to determine, by transmission electron microscopy, the differentiation features of 21 human malignant mesothelioma cell lines (HMCLs) established from 13 specimens of 12 confirmed human malignant mesotheliomas, and of tumours induced in nude mice injected with 16 HMCLs. Fifty per cent of HMCLs showed typical mesothelial differentiation (long and slender microvilli, desmosomes, perinuclear intermediate filaments); 29 per cent did not show differentiation; and the remainder were poorly differentiated. Three human tumour specimens gave several different HMCLs; the cell lines obtained from a given tumour exhibited variable mesothelial differentiation. Eleven HMCLs were compared with the native tumour. Four were similar to the tumour and seven were less well differentiated, in most cases in relation to their microvilli. With six HMCLs, tumours induced in nude mice were less well differentiated than the corresponding cell lines, whereas with four HMCLs, tumours were equally or better differentiated. However, in most nude mice tumours, typical mesothelial microvilli were present. These results show that cell lines established from malignant mesothelioma may exhibit dedifferentiated features. However, while the variability in ultrastructural differentiation may result from the culture microenvironment, it could also be related to the state of differentiation, of the native tumour sample and to tumour cell heterogeneity.

Animals↗

Scoliosis in spinal muscular atrophy: review of 63 cases.

We reviewed the incidence and severity of scoliosis in 37 patients with the intermediate type and 26 with the mild type of spinal muscular atrophy. In the intermediate type, scoliosis has an early onset and rapid progression before puberty, and a spinal fusion will be needed in virtually all cases. This rapid progression occurred despite routine use of a spinal brace. Hip dislocation was frequently present but, in most cases, was secondary to the pelvic tilt and did not contribute to the scoliosis. In the mild type, the scoliosis was more variable. In the 30% of patients who had scoliosis, progression was rapid during puberty but only in those who had lost ambulation. Of the four children with the intermediate type and the seven with the mild type who walked in light-weight orthoses, progression of scoliosis was slow, except in those who had lost ambulation. The ultimate effect of walking in orthoses is difficult to assess because of small numbers, but it seems to slow or at least delay progressive scoliosis.

Adolescent↗

The long-term within- and between-laboratory variability for assay of antithrombin, and proteins C and S: results derived from the external quality assessment program for thrombophilia screening of the ECAT Foundation.

A stable laboratory performance is important for comparability and transferability of laboratory data both within and between laboratories. The lack of a reference system within hemostasis hampers laboratories in establishing their laboratory performance over a prolonged period of time. Therefore, based on data from an external quality assessment program, we evaluated the between laboratory variation (CVBETWEEN) and the long-term within-laboratory variation (LCVa) for antithrombin, and proteins C and S. We evaluated the CVBETWEEN for the period 1996-2001, including the results of 64-240 laboratories from 23 different surveys (protein S activity 15 surveys). We observed a quite high CVBETWEEN and a broad range for each analyte. The CVBETWEEN was significantly higher for antithrombin and protein S for samples with low levels similar to heterozygous deficiencies. We also evaluated the LCVa, including the results of 136 laboratories. The lowest LCVa[median and 95% content interval (CI)] was observed for antithrombin (7.6%; 3.6-35.5%), intermediate values for protein C activity and antigen (8.6%; 3.5-25.3% and 10.8%; 4.8-33.1%, respectively) and highest values for the protein S variables (13.4%; 6.4-50.6% for total protein S antigen, 14.1%; 6.5-79.1% for free protein S antigen and 17.2%; 7.2-84.3% for protein S activity). We concluded that the main reason for the high CVBETWEEN is the long-term within-laboratory variability. Application of linear regression on data of an external quality assessment program is a useful model to demonstrate per analyte per laboratory the long-term variability (LCVa). It is concluded that improvement of the long-term within-laboratory test performance is the first priority in hemostasis to yield important improvements in the comparability and transferability of laboratory data.

Antithrombin III↗

Bis(acetylacetonato)tricarbonyl tungsten(II): a convenient precursor to chiral bis(acac) tungsten(II) complexes.

Two equivalents of acetylacetonate (acac) have been successfully introduced into a monomeric tungsten(II) coordination sphere. With the tetracarbonyltriiodotungsten(II) anion as a precursor, the formation of a tungsten(II) bis(acac) tricarbonyl complex, W(CO)3(acac)2, 1, has been accomplished. The addition of PMe3 or PMe2Ph to tricarbonyl complex 1 formed tungsten(II)bis(acac)dicarbonylphosphine complexes 2a and 2b, respectively. Single-crystal X-ray diffraction studies of the parent tricarbonyl complex, 1, and dicarbonyl trimethylphosphine complex 2a confirmed seven-coordinate geometries for both complexes. Variable-temperature 1H and 13C{1H} NMR spectroscopy revealed fluxional behavior for these seven-coordinate molecules: rapid exchange of the three carbon monoxide ligands in 1 was observed, and movement of the phosphine ligand through a mirror plane in a C(S) intermediate species was observed for both 2a and 2b. Tricarbonyl complex 1 reacted readily with alkyne reagents to form bis(acac)monocarbonylmonoalkynetungsten(II) complexes 3a (PhC(triple bond)CH) and 3b (MeC(triple bond)CMe). Variable-temperature 1H NMR spectroscopy was used to probe rotation of the alkyne ligand in 3a and 3b. The introduction of two alkyne ligands was accomplished thermally using excess PhC(triple bond)CPh to form bis(alkyne) complex 4 which was characterized crystallographically, as well as by 1H and 13C NMR spectroscopy. The availability of W(CO)3(acac)2 as a source of the W(acac)2 d4 moiety lies at the heart of the chemistry reported here.

Journal Article↗

Spatial heterogeneity in parasite infections at different spatial scales in an intertidal bivalve.

Spatial heterogeneities in the abundance of free-living organisms as well as in infection levels of their parasites are a common phenomenon, but knowledge on parasitism in invertebrate intermediate hosts in this respect is scarce. We investigated the spatial pattern of four dominant trematode species which utilize a common intertidal bivalve, the cockle Cerastoderma edule, as second intermediate host in their life cycles. Sampling of cockles from the same cohort at 15 sites in the northern Wadden Sea (North Sea) over a distance of 50 km revealed a conspicuous spatial heterogeneity in infection levels in all four species over the total sample as well as among and within sampling sites. Whereas multiple regression analyses indicated the density of first intermediate upstream hosts to be the strongest determinant of infection levels in cockles, the situation within sites was more complex with no single strong predictor variable. However, host size was positively and host density negatively correlated with infection levels and there was an indication of differential susceptibility of cockle hosts. Small-scale differences in physical properties of the habitat in the form of residual water at low tide resulted in increased infection levels of cockles which we experimentally transferred into pools. A complex interplay of these factors may be responsible for within-site heterogeneities. At larger spatial scales, these factors may be overridden by the strong effect of upstream hosts. In contrast to first intermediate trematode hosts, there was no indication for inter-specific interactions. In other terms, the recruitment of trematodes in second intermediate hosts seems to be largely controlled by pre-settlement processes both among and within host populations.

Animals↗

A preliminary multi-stable-isotopic evaluation of three synthetic pathways of Topiramate.

As a preliminary study of the utility of the natural stable-isotopic differentiation of batch samples produced by different synthetic pathways, multi-stable-isotopic analyses (delta(13)C, delta(15)N, delta(18)O, deltaD) of 53 samples of the antiepileptic drug, Topiramate, produced by three different synthetic pathways (designated "A," "B," "C") were performed. From the outset, we note that there are two fundamental variables that determine the stable-isotopic composition of materials-the stable-isotopic composition of the reagents and starting intermediates, and the isotope fractionation that occurs during manufacture of the product. In this study, the stable-isotopic composition of the raw materials was not controlled and we report here data obtained for a suite of samples that was produced by three synthetic pathways. Graphical examination of these data reveals marked data clustering by synthetic pathway, though in some cases with some overlapping values within standard errors. In general, the isotopic composition of Topiramate from the A and B pathways is distinct from the C pathway. The isotopic data from the A and B pathways typically abut each other, sometimes partially overlapping. The deuterium/hydrogen- (deltaD) and oxygen (delta(18)O) isotopic compositions are each significantly linearly related with the paired carbon (delta(13)C) isotopic composition indicating possible isotopic end-members for the raw materials of the present sample suite. Given that H and O typically derive from meteoric water, the linear correlations with delta(13)C indicate that a mixture of carbon sources (viz., perhaps terrestrial C3 photosynthetic organic carbon and marine C3 organic carbon) were used in the production of the batches tested. If the H and O analyzed were derived from meteoric water, then an elementary comparison of the span of the deltaD (DeltadeltaD = 54.6 +/- 2.1 per thousand) and of the delta(18)O (Deltadelta(18)O = 4.71 +/- 0.26 per thousand) values in the Topiramate samples to that of the global isotopic gradients indicates that the water retained in the samples spanned from as much as 11 degrees of latitude (or, approximately 760 statute miles North-to-South). The present isotope results (delta(13)C, delta(15)N, delta(18)O, deltaD) form an initial database against which future samples can be compared to infer specific synthetic pathways. It is clear that to perform a rigorous test of the variables controlling the stable-isotopic composition of pharmaceutical materials that both the stable-isotopic composition of the starting materials and synthetic isotope fractionation must be controlled in future studies.

Fructose↗

Climate change may account for the decline in British ring ouzels Turdus torquatus.

1. Climate change is already affecting biodiversity, but the number of species for which reliable models relate weather and climate to demographic parameters is low. 2. We modelled the effect of temperature and rainfall on the breeding success and territory occupancy of ring ouzels Turdus torquatus (L.) in northern Britain, using data from a range of study areas, including one where there was a long-term decline in ring ouzel abundance. 3. Timing of breeding was significantly related to meteorological variables affecting birds in the early spring, though there was no evidence that laying dates had advanced. Breeding success was not significantly related to weather variables; instead, over 90% of annual variation in this parameter could be explained by density dependence. 4. Annual change in territory occupancy was linked to rainfall and temperature the preceding summer, after the main breeding season and to rainfall in the wintering grounds 24 months previously, coincident with the period of juniper Juniperus sp. (L.) flowering. High temperature in late summer, intermediate levels of late summer rainfall, and high spring rainfall in Morocco 24 months previously all had negative impacts on territory occupancy the following year. 5. All three weather variables have changed over recent decades, with a significant increase in summer temperature, a significant decrease in summer rainfall, and a nonsignificant decline in Moroccan spring rainfall. A model based on these trends alone predicted an annual decline in occupancy of 3.6% (compared with an observed decline of 1.2%), and suggested that increased summer temperatures may underlie declines in the British ring ouzel population. 6. Changes in summer temperature after the main breeding period could affect the survival rates of adult and/or juvenile birds. An improved understanding of the post-breeding ecology of ring ouzels is required to elucidate the mechanisms and causes of this relationship. Such knowledge might allow management aimed at buffering the impacts of climate change on ring ouzels.

Animal Migration↗

Prognostic value of the Duke treadmill score in the elderly.

OBJECTIVES: The purpose of this study was to test the hypothesis that the Duke treadmill score works less well for risk stratification in patients age 75 years or above. BACKGROUND: Although the Duke treadmill score is generally effective for risk stratification, its prognostic value in the elderly may be limited because they have a higher prevalence of coronary artery disease (CAD), more severe CAD and a lower exercise tolerance. METHODS: The study population consisted of 247 patients age 75 years or above, and the control population consisted of 2,304 patients below 75 years of age. All patients were symptomatic, had undergone exercise thallium testing between 1989 and 1991 and were followed for a median of >6.5 years. The Cox regression model was used to test the association of the Duke score (utilized both as a continuous variable and using previously published risk group cutoffs) with outcomes (cardiac death, nonfatal myocardial infarction [MI], late revascularization). RESULTS: Using the Duke score to risk-stratify the elderly, 26% were in the low risk group, 68% were in the intermediate risk group and 6% were in the high risk groups; seven-year cardiac survival was 86%, 85% and 69%, respectively (p = 0.45). There was also no significant association between these Duke score risk groups and all other outcome end points in the elderly. The Duke score as a continuous variable did not predict cardiac death (p = 0.43) or cardiac death or MI (p = 0.42), but did predict total cardiac events (which included late revascularization) (p = 0.0027). For the control population, more patients (55%) were in the low risk group, and the Duke score (as a continuous variable or in risk groups) was highly predictive of all end points (p = 0.0001). CONCLUSIONS: The Duke score predicted cardiac survival in younger patients but not in patients age 75 years or above. The majority of the elderly were classified as intermediate risk by the Duke score. Only a minority of the elderly were classified as low risk, but this group still had an annual cardiac mortality of 2%/year.

Age Factors↗

Gastric non-Hodgkin's lymphoma: analysis of 252 patients from a multicenter study.

AIMS AND BACKGROUND: The stomach is the most common site of primary extranodal non-Hodgkin's lymphoma (NHL) and no agreement has been reached so far on the best therapeutic approach. The main objects of this study were to report the long-term results and to evaluate the importance of some possible prognostic factors in a large series of patients. NHL was considered primary gastric if the main symptoms at presentation were those of gastric disease. METHODS AND STUDY DESIGN: We analyzed 252 consecutive patients treated between 1980 and 1993 in five hospitals in north-east Italy. According to the Working Formulation, 98 patients had low grade lymphoma, 59 intermediate grade (D to F), 81 G or high grade and 14 were not classified. The patients were divided into two groups: one including patients with limited disease (localized to the stomach or perigastric lymph nodes: 165 patients) and one including those with advanced disease (87 patients). The treatment consisted of surgery, chemotherapy, radiotherapy or combinations of these. Sixteen patients received only supportive therapy. RESULTS: The five-year overall survival was 65.4%: 80.3% for patients with limited disease and 36.7% for those with advanced disease (P < 0.0001). Among the limited disease patients the five-year survival was 84.4% for those treated with gastrectomy alone and 88.7% for those who received also adjuvant chemotherapy (P = 0.11). However, while chemotherapy did not improve survival in low grade NHL, it seemed to produce a better survival in the intermediate and high grade groups (P = 0.06). Twelve patients were treated with primary chemotherapy and the five-year survival was 71.2%. In multivariate regression analysis the most important variable for overall survival was surgery for the whole group of 252 patients (P < 0.0001), while it was age for the group with limited disease (P = 0.0008). CONCLUSIONS: Surgery alone can be curative for most patients with gastric lymphoma limited to the stomach or to the perigastric lymph nodes; surgery followed by chemotherapy seems to produce better results than surgery alone in intermediate and high grade lymphomas. Also a non-surgical approach with first-line chemotherapy is associated with a high rate of complete remissions and five-year survival. In advanced disease the five-year survival is similar to that of nodal NHL.

Adolescent↗

Adequacy of prenatal care and pregnancy outcome.

The objective of this study was to determine whether a relationship exists between adequacy of prenatal care and preterm delivery, low-birth-weight, and small-for-gestational-age infants. Data from 1771 patients enrolled in an ongoing study of maternal growth in young gravidas were studied. The indices of both Kessner and colleagues (the Kessner index) and Kotelchuck (the Kotelchuck index) were used to determine adequacy of prenatal care. Patients receiving adequate care were compared with those receiving intermediate or inadequate care and the incidence of preterm birth, low-birth-weight, and small-for-gestational-age infants was determined in each group. The study controlled for potential confounding variables, that is, black ethnicity, maternal age, pregravid body mass index, parity, adequate prenatal weight gain, smoking, and previous delivery of low-birth-weight or preterm infant. The data were analyzed by logistic regression. When classified according to the Kessner index, 290 (16.4%) of the women received inadequate care, 961 (54.3%) received intermediate care, and 520 (29.4%) received adequate care. By the Kotelchuck index, 651 (36.8%) of the women received inadequate care, 201 (11.3%) received intermediate care, 604 (34.1%) received adequate care, and 315 (17.8%) received adequate-plus care. By use of the Kessner index and by estimating gestation from the last menstrual period, it was determined that women who received inadequate care had a 2.8 times greater risk (95% confidence interval [CI], 2.07-3.78), and by use of the Kotelchuck index, a 2.1 times greater risk (95% CI, 1.58-2.81) of having a preterm delivery. When the obstetric estimate of gestation was used, risk was 2.01 times greater (95% CI, 1.44-2.80) with the Kessner index and 1.4 times greater (95% CI, 1.0-1.94) with the Kotelchuck index. There was little effect of prenatal care on incidence of small-for-gestational-age infants. The results of this study confirmed that inadequate prenatal care is associated with an increased risk of preterm delivery.

Adolescent↗

Global analysis of three-state protein unfolding data.

A new method for analyzing three-state protein unfolding equilibria is described that overcomes the difficulties created by direct effects of denaturants on circular dichroism (CD) and fluorescence spectra of the intermediate state. The procedure begins with a singular value analysis of the data matrix to determine the number of contributing species and perturbations. This result is used to choose a fitting model and remove all spectra from the fitting equation. Because the fitting model is a product of a matrix function which is nonlinear in the thermodynamic parameters and a matrix that is linear in the parameters that specify component spectra, the problem is solved with a variable projection algorithm. Advantages of this procedure are perturbation spectra do not have to be estimated before fitting, arbitrary assumptions about magnitudes of parameters that describe the intermediate state are not required, and multiple experiments involving different spectroscopic techniques can be simultaneously analyzed. Two tests of this method were performed: First, simulated three-state data were analyzed, and the original and recovered thermodynamic parameters agreed within one standard error, whereas recovered and original component spectra agreed within 0.5%. Second, guanidine-induced unfolding titrations of the human retinoid-X-receptor ligand-binding domain were analyzed according to a three-state model. The standard unfolding free energy changes in the absence of guanidine and the guanidine concentrations at zero free-energy change for both transitions were determined from a joint analysis of fluorescence and CD spectra. Realistic spectra of the three protein states were also obtained.

Animals↗

Intraarticular pressure during continuous passive motion of the human knee.

Intraarticular pressure (IAP) was continuously monitored during continuous passive motion (CPM) of five normal and 11 abnormal human knees using a new fiberoptic, transducer-tipped Camino catheter. IAP varied in a consistent hysteresis pattern in the normal knees, with subatmospheric pressures recorded at intermediate angles of joint flexion. A similar pattern was recorded in the abnormal knees without cruciate ligament pathology, whereas considerable variability was noted in the knees with cruciate ligament abnormality. IAP was lower in the extension to flexion than in the flexion to extension portion of the CPM cycle, providing evidence of intraarticular fluid flow during portions of the CPM cycle. IAP changes were consistent with "physiologic compartmentation" within the knee at extremes of joint position. Capsular viscoelastic changes and/or synovial fluid volume changes were observed during CPM. The therapeutic mechanism of continuous passive motion may be related to cyclic variation of the intraarticular pressure.

Adult↗

Ultrastructural characteristics of inclusion bodies of type II cells in late embryonic mouse lung.

As we reported earlier, type II alveolar epithelial cells make their appearance in the early embryonic mouse lung around day 14.2, and show distinctive ultrastructural features. The present study focuses on the ultrastructural characteristics of the inclusion bodies by investigating embryos aged 17-19 days (birth on day 19), using transmission electron microscopy. Late embryonic type II cells appear also as low-columnar or cuboid cells having large, approximately round nuclei and cytoplasm displaying typical features of a differentiated cell. The inclusion bodies show a widespread distribution and are extremely variable in appearance. Schematically we discern five main types, namely cytoplasmic, granular/flocculent, multivesicular, dense, and (multi)lamellar, which occur with intermediate and composite forms. All these inclusion bodies frequently contain glycogen particles, and show a structural relation to profiles of endoplasmic reticulum which are wrapped around them. Other distinctive properties are the osmiophily of multivesicular inclusion bodies, and the presence of vesicles in many dense inclusion bodies. The possible interrelationship, and the differences in various aspects of electron density, suggest that the five main types of inclusion bodies may represent different stages in the formation of mature multilamellar bodies.

Animals↗