Performance of basic strategies for following gradients in two dimensions.

Computer models for following stimulus gradients in two-dimensional space were evaluated to determine the relative advantages of different strategies and to identify the issues that must be addressed in making such a comparison. The simulations were implemented with emphasis on making them as general and free of specific assumptions as possible. Performance was defined as progress along the gradient divided by the cost of the movements and time taken. Plausible values of costs were taken from data on animal energetics. The models also included various kinds of noise that limit performance. These included unintended variations and biases in motor outputs as well as sensory inputs. An initial guess at appropriate noise levels led to performance worse than that observed in experiments with leukocytes. Reduced noise levels gave good agreement. Under these, more appropriate, conditions, peak performance for the various models varied from 24 to 99% of the maximum possible. The threshold gradient required to provide performance equal to 1% of the maximum possible varied from 800 to 5000 searcher diameters per gradient decay length. Some models performed well only over a narrow range of gradients. There was no indication of a tradeoff between sensitivity to shallow gradients and high performance in steep gradients. The model of tropotaxis (simultaneous, spatial comparison) with movement in any direction was superior in having the lowest threshold, the highest maximum performance, requiring the fewest parameters to fit, and performed well over the widest range of gradients. This result suggests that amoeboid cells and echinoderms might be particularly well suited to following gradients. The modeling demonstrates the need to obtain quantitative estimates for a number of parameters (relating costs and noise levels) for a more rigorous understanding of the relative advantages of these different strategies.

Selection for high gamete encounter rates explains the success of male and female mating types.

Sexual reproduction occurs in many small eukaryotes by fusion of similar gametes (isogamy). In the absence of distinguishable sperm and eggs, male and female mating types are missing. However, species with distinct males and females have so prospered that almost all familiar plants and animals have these mating types. Why has sexual reproduction involving sperm and eggs been so successful? An answer is obtained by considering physical limitations on encounter rates between gametes. A biophysical model based on well-established relationships produces fitness landscapes for the evolution of gamete size and energy allocation between motility and pheromone production. These landscapes demonstrate that selection for high gamete encounter rates favors large, pheromone-producing eggs and small, motile sperm. Thus, broadcast-spawning populations with males and females can reproduce at lower population densities and survive under conditions where populations lacking males and females go extinct. It appears that physical constraints on gamete encounter rates are sufficient to explain the first two steps in the isogamy-->anisogamy-->oogamy-->internal fertilization evolutionary sequence observed in several lineages of the eukaryotes. Unlike previous models, assumptions concerning zygote fitness or decreasing speed of swimming with increasing gamete size are not required.

Comparison of lethality, reproduction, and behavior as toxicological endpoints in the nematode Caenorhabditis elegans.

This study describes a new approach for assessing behavioral changes following toxicant exposure and compares the method to other common endpoints used in environmental toxicology. The nematode Caenorhabditis elegans was exposed to a range of ethanol concentrations to determine its effect on survival, reproduction and behavior. Each endpoint was evaluated for its sensitivity by comparing LC50, RC50 (concentration at which there is a 50% reduction in number of offspring as compared to controls), and BC50 (concentration at which there is a 50% reduction in movement as compared to controls) values for ethanol exposure. Worms showed 24-h lethality at concentrations of ethanol in the range of 83 g/L to 99 g/L. Reproduction in C. elegans was estimated by counting the number of off-spring after 3 d of exposure, which decreased with the increase in ethanol concentration from 8 g/L to 71 g/L. Behavior was quantified by using a new computer tracking method, which can simultaneously assess hundreds of nematodes and provides several behavioral parameters in real time. Worms showed some hyperactivity (increased movement) at very low ethanol concentrations (0.8 g/L and 2.4 g/L) and a decrease in movement at higher ethanol concentrations (4 g/L to 40 g/L). A comparison for sensitivity between the three endpoints was performed. Behavior and reproduction responses were found to be similar and, as expected, both are much more sensitive indicators of toxicity than lethality. The advantages and disadvantages of the computer tracking system are discussed.

Fitness landscapes for effects of shape on chemotaxis and other behaviors of bacteria.

Data on the shapes of 218 genera of free-floating or free-swimming bacteria reveal groupings around spherical shapes and around rod-like shapes of axial ratio about 3. Motile genera are less likely to be spherical and have larger axial ratios than nonmotile genera. The effects of shape on seven possible components of biological fitness were determined, and actual fitness landscapes in phenotype space are presented. Ellipsoidal shapes were used as models, since their hydrodynamic drag coefficients can be rigorously calculated in the world of low Reynolds number, where bacteria live. Comparing various shapes of the same volume, and assuming that departures from spherical have a cost that varies with the minimum radius of curvature, led to the following conclusions. Spherical shapes have the largest random dispersal by Brownian motion. Increased surface area occurs in oblate ellipsoids (disk-like), which rarely occur. Elongation into prolate ellipsoids (rod-like) reduces sinking speed, and this may explain why some nonmotile genera are rod-like. Elongation also favors swimming efficiency (to a limited extent) and the ability to detect stimulus gradients by any of three mechanisms. By far the largest effect (several hundred-fold) is on temporal detection of stimulus gradients, and this explains why rod-like shapes and this mechanism of chemotaxis are common.

Spatial sensing of stimulus gradients can be superior to temporal sensing for free-swimming bacteria.

Predictions of the minimal size an organism must have to swim along stimulus gradients were used to compare the relative advantages of sensory systems employing spatial (simultaneous) and temporal (sequential) gradient detection mechanisms for small free-swimming bacteria, leading to the following conclusions: 1) there are environmental conditions where spatial detection mechanisms can function for smaller organisms than can temporal mechanisms, 2) temporal mechanisms are superior (have a smaller size limit) for the difficult conditions of low concentration and shallow gradients, but 3) observed bacterial chemotaxis occurs mostly under conditions where spatial mechanisms have a smaller size limit, and 4) relevant conditions in the natural environment favor temporal mechanisms in some cases and spatial mechanisms in others. Thus, sensory ecology considerations do not preclude free-swimming bacteria from employing spatial detection mechanisms, as has been thought, and microbiologists should be on the lookout for them. If spatial mechanisms do not occur, the explanation should be sought elsewhere.

Minimum size limit for useful locomotion by free-swimming microbes.

Formulas are derived for the effect of size on a free-swimming microbe's ability to follow chemical, light, or temperature stimuli or to disperse in random directions. The four main assumptions are as follows: (i) the organisms can be modeled as spheres, (ii) the power available to the organism for swimming is proportional to its volume, (iii) the noise in measuring a signal limits determination of the direction of a stimulus, and (iv) the time available to determine stimulus direction or to swim a straight path is limited by rotational diffusion caused by Brownian motion. In all cases, it is found that there is a sharp size limit below which locomotion has no apparent benefit. This size limit is estimated to most probably be about 0.6 micron diameter and is relatively insensitive to assumed values of the other parameters. A review of existing descriptions of free-floating bacteria reveals that the smallest of 97 motile genera has a mean length of 0.8 micron, whereas 18 of 94 nonmotile genera are smaller. Similar calculations have led to the conclusion that a minimum size also exists for use of pheromones in mate location, although this size limit is about three orders of magnitude larger. In both cases, the application of well-established physical laws and biological generalities has demonstrated that a common feature of animal behavior is of no use to small free-swimming organisms.

Cytologic features of post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorders (PTLD) are Epstein-Barr virus (EBV)-associated lymphoid proliferations which affect approximately 2% of organ allograft recipients. Although the histologic features of PTLD are well described, they have been described only rarely in cytologic specimens. The cytomorphologic features of PTLD in body fluid specimens, needle aspirations, and a gastric brushing specimen from seven patients with histologically confirmed PTLD were therefore reviewed. In the cytologic specimens, PTLD was characterized by a mostly polymorphous population of lymphoid cells containing many large transformed lymphocytes, occasional immunoblast-like atypical lymphocytes, necrosis, and, frequently, obvious plasmacytoid differentiation. The presence of EBV was documented in five of the seven cases in the corresponding tissue biopsies. The four patients with PTLD in a body fluid specimen all died within 3 months of detection of the PTLD in the body fluid. The three remaining patients are alive with resolution of PTLD (follow-up of 7, 8, and 14 months). The diagnosis of PTLD should be suggested when cytologic specimens from organ allograft recipients show a polymorphous atypical lymphoid proliferation, frequently with plasmacytoid differentiation and necrosis. Cytologic samples may provide the initial diagnosis of this potentially fatal disease and allow appropriate intervention. The presence of PTLD in a body fluid specimen is a poor prognostic indicator.

Histocytologic diagnosis of neuroendocrine tumors in the liver: a retrospective study of 23 cases.

A series of 23 needle biopsies of neuroendocrine tumors occurring in the liver is described. Aspirate smears, core biopsies, and touch preparations were examined. Eighteen of the 23 patients had been previously diagnosed: 9 patients had been correctly identified as having a neuroendocrine tumor, and 9 patients had been originally misdiagnosed. Five of the patients in this series had no previously identified neoplasia. Immunohistochemical staining confirmed the neuroendocrine nature of the tumors in each of the cases. On the basis of cytomorphology, these cases were subtyped as either round cell type, spindle cell type, or polygonal cell type. The polygonal cell type of neuroendocrine tumor, as well as rare examples of the round cell type, demonstrated features similar to well-differentiated hepatocellular carcinoma and adenocarcinomas, and may present a diagnostic dilemma. Characteristic cytologic attributes of the polygonal cell type of neuroendocrine tumor which aid in its distinction from well-differentiated hepatocellular carcinoma include eccentrically located "plasmacytoid" nuclei and cellular discohesion. Findings on core needle biopsy which further identify the neuroendocrine tumors are thick fibrous stroma or small "nests" of tumor cells. The additional use of immunohistochemical staining provides reliable evidence of the cell of origin in confusing cases. Attention to these considerations will aid in the cytologic diagnosis of neuroendocrine tumors.

Combined hepatocellular-cholangiocarcinoma. Cytologic findings in four cases.

BACKGROUND: Rarely do primary hepatic tumors show mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma differentiation. Histologic criteria for these combined hepatocellular-cholangiocarcinomas (CHCC-C) are not universally agreed upon. Cytologic descriptions of CHCC-C are scarce, yet recognition of this tumor type may have some prognostic significance. CASES: The clinical and cytohistologic findings, including histochemical and immunohistochemical studies, in four cases of CHCC-C were reviewed. The specimens consisted of three needle biopsies of the liver and one bile duct brushing specimen. In all cases the diagnosis of CHCC-C was confirmed by histologic, histochemical and immunohistochemical study. CONCLUSION: The reliable diagnosis of CHCC-C on cytologic preparations alone is fraught with difficulty. However, the addition of cell block or core biopsy histologic material, which may serve as a substrate for histochemical and immunohistochemical studies, may permit the diagnosis to be made. Serum markers of HCC, when elevated, may raise the suspicion of hepatocellular differentiation even when it is not suspected based on examination of the cytologic and/or histologic biopsy specimen.

Fine needle aspiration of pleomorphic adenoma and adenoid cystic carcinoma of salivary gland origin.

OBJECTIVE: To determine the cytologic similarities, distinctive features and diagnostic problems on fine needle aspiration in patients with pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) of salivary gland origin. STUDY DESIGN: We reviewed the preoperative cytology and histologic sections in 22 patients in whom the resected specimens were diagnosed as PA (17 cases) or ACC (5 cases) of salivary gland. RESULTS: Concordant results were noted between cytologic and histologic diagnoses in 20 cases (91%) and discordant results in 2 cases (9%). Both discordant aspirates had been diagnosed as PA; however, their resected specimens were diagnostic of ACC. Although there were cytologic features common to both tumors, each had a unique relationship of epithelial cells to stroma. Aspirates in PA showed cell clusters with a "sunburst" appearance caused by peripheral spindled cells streaming into a fibrillar myxoid stroma. In ACC well-delineated, tightly cohesive, basaloid cells surrounded mucoid/hyaline globules or clear spaces in a honeycomb pattern. CONCLUSION: The cytologic distinction between PA and ACC in most cases was easily made on adequately cellular aspirates. In the two aspirates with discordant results, diagnostic difficulty resulted when the distinctive relationship between epithelial cells and extracellular matrix was not recognized in sparsely cellular specimens, in part due to lack of observer familiarity with the different patterns.

Biliary stricture due to hepatocellular carcinoma: diagnosis by bile duct brushing cytology.

Bile duct brushing cytology is a useful technique in the diagnosis of malignant biliary strictures. Adenocarcinoma is the usual type of carcinoma diagnosed in these brushing specimens. This report details the bile duct brushing cytology findings in an unusual case of hepatocellular carcinoma which presented with obstructive jaundice due to invasion of the biliary tract. A striking feature of the brushing was the prominent capillary vascular pattern associated with the tumor cells. This is a cytologic feature which has been noted in fine-needle aspirates of hepatocellular carcinoma as well, and is distinct from the expected findings in adenocarcinoma.

Spindle-cell thymic carcinoid occurring in multiple endocrine neoplasia I: fine-needle aspiration findings in a case.

Thymic carcinoid tumors are important to distinguish from thymomas because of their worse prognosis. These rare tumors occasionally occur in the setting of multiple endocrine neoplasia (MEN). A needle biopsy was performed on a 57-yr-old woman with MEN I and a newly-discovered anterior mediastinal mass. Aspiration smears were cellular and contained polygonal-to-spindled cells with high nucleocytoplasmic ratios and evenly-dispersed pattern. Occasional nuclear molding and rosette-like arrangements were present. A synaptophysin immunostain was positive on cell-block preparation. A diagnosis of thymic carcinoid was made. Subsequent excision of the mass confirmed the diagnosis of thymic carcinoid. Thymic carcinoids are cytologically similar to carcinoid tumors elsewhere. They should be distinguished from epithelial thymoma and substernal medullary carcinoma of the thyroid.

Fine-needle aspiration biopsy findings in a case of follicular dendritic cell tumor.

Follicular dendritic cells (FDCs) are non-lymphoid immune accessory cells found in follicles of lymph nodes. Tumors purported to arise from FDCs have recently been described and are considered rare. Histologically, these tumors show an admixture of large, spindled cells and benign lymphocytes. The large cells display a syncytial growth pattern, have delicate chromatin, and, in part, are defined by their expression of complement receptors. The authors recently observed the fine-needle aspiration (FNA) cytologic findings in a case that was subsequently proven to be a FCD tumor. Direct smears exhibited a dimorphic cellular pattern composed of large pale cells admixed with small lymphocytes. The large cells had delicate chromatin, inconspicuous nucleoli, and nuclear membrane infoldings, including occasional cytoplasmic protrusions into the nucleus. The cells were arranged singly and in syncytial groups. These cytologic findings may be characteristic enough to suggest the diagnosis of FDC tumor. Immunocytochemical confirmation should be sought in such cases.

Cytology of hepatocellular carcinoma in serous fluids: a report of three cases.

Three cases of hepatocellular carcinoma (HCC) detected in serous fluids are reported. Two cases were detected in ascitic fluid and one case was identified in pleural fluid of a patient with widespread disease. The cytopathologic findings correlated well with the histologic type in each case. One case each of moderately differentiated, poorly differentiated, and fibrolamellar HCC were seen. In general, the fluids contained large polygonal cells, singly and in small clusters with large vesicular, occasionally multiple nuclei and prominent nucleoli. The current literature describing HCC in serous fluids is sparse. The identification of this tumor in serous fluids would allow diagnosis of new or recurrent disease and have implications for therapy.

Fine-needle aspiration cytology of metastatic ovarian carcinoma to the breast.

Metastatic ovarian carcinoma to the breast is rare. It represents a diagnostic challenge to the cytologist. It usually signifies a progressive widespread metastatic ovarian tumor with a poor prognosis. This report evaluates the breast fine-needle aspiration (FNA) cytomorphologic features of six cases of metastatic ovarian carcinoma and compares them to those reported in the literature. The cytologic features included hypercellularity, abundant papillary fragments, and necrotic background. The tumor cells showed high nuclear/cytoplasmic ratio, anisonucleosis, prominent nucleoli, and psammoma bodies in cases of serous papillary carcinoma. In addition, the clear-cell carcinoma had prominent finely vacuolated and clear cytoplasm, multinucleated giant cells, and papillary fragments with hobnail nuclei. Recognition of these unusual patterns in a breast FNA cytology should raise the suspicion of a metastatic ovarian tumor. Direct comparison between the breast FNA cytology and the original primary ovarian tumor should confirm the diagnosis. The proper diagnosis of metastatic ovarian cancer to the breast will prevent unnecessary surgical treatment and ensure the appropriate therapy.

Fine needle aspiration diagnosis of hepatocellular carcinoma in metastatic sites.

OBJECTIVE: To describe the fine needle aspiration (FNA) findings in metastatic hepatocellular carcinoma (HCC). STUDY DESIGN: The cytologic findings in 15 cases of extrahepatic metastatic HCC diagnosed by FNA biopsy were reviewed. RESULTS: The anatomic sites of the FNAs were: musculoskeletal (four biopsies from 3 patients), adrenal (4 patients), regional lymph nodes (4 patients), pancreas (2 patients) and pelvic region (1 patient). The 15 aspirates came from 14 patients, 11 of whom had a biopsy-proven primary HCC. In two of the remaining patients, the FNA diagnosis of HCC in the metastatic site was the initial diagnosis. In one of these patients the diagnosis was strongly suspected on clinical grounds, but in the other case it was unsuspected. In the remaining patient the liver mass and massive retroperitoneal adenopathy were biopsied concurrently. A trabecular pattern was observed in the smears and/or cell block preparations in nine cases. Eleven cases were well to moderately differentiated. Three cases were of large cell pleomorphic type. The remaining case was poorly differentiated. CONCLUSION: Familiarity with the FNA cytology of HCC should allow its diagnosis in metastatic sites in most instances, even without a history of primary liver cancer.

Needle biopsy of the adrenal gland: retrospective review of 54 cases.

A retrospective review of 54 cases of adrenal gland needle biopsy in 53 patients is presented. The cases included 43 fine-needle aspirations (FNA), six core-needle biopsies, and five cases in which both types of needle biopsy were done. Clinical or histologic follow-up was available in 28 of the 36 specimens deemed adequate for evaluation. Metastatic malignancies represented the largest group of cases (19), with lung being the most common primary site (8). The series included four cases of metastatic hepatocellular carcinoma. Probable adrenocortical adenoma was the next most common diagnosis (12 cases). Cases causing diagnostic confusion included a case of metastatic well-differentiated hepatocellular carcinoma which was initially confused with an adrenocortical adenoma and a probable adrenocortical adenoma which was mistaken for a metastatic small round cell malignancy. (This case is unproved because of lack of clinical or histologic follow-up). By evaluating only those cases with histologic confirmation or clinical follow-up greater than one year, the sensitivity of needle biopsy for the presence of malignancy was 95% and the specificity was 100%. The cytologic findings are described with attention to the potential problem of confusing primary adrenocortical neoplasms with metastases from hepatocellular carcinoma.

Threshold chemosensitivity and hypothetical chemoreceptor function of the nematodeCaenorhabditis elegans.

The behavioral responses by the nematodeCaenorhabditis elegans to 12 organic compounds was explored using tethered nematode and computer tracking methods. Results indicate that the nematode is attracted to acetone, diethyl ether, isoamyl acetate, isoamyl alcohol, 2,4-pentanedione, andn-propanol. No responses were detected to acetaldehyde, acetylcholine, ethanol, formaldehyde, i-propanol, and valerate. Isoamyl acetate and acetone were found to be the most potent attractants eliciting minimal responses at concentrations near 10(-10) M. The geometry and charge distribution of a single hypothetical receptor that would interact with all the compounds that elicited a response and none of the compounds that failed to elicit a response is explored.