Differentiation of neutrophil-like HL-60 cells strongly impacts their rolling on surfaces with various adhesive properties under a pressing force.

BACKGROUND: HL-60 cells have been used in in vitro experiments of neutrophils rolling. They lose uniform spherical appearance and enhance deformability by differentiation to neutrophil-like cells, which would affect their rolling characteristics. OBJECTIVE: We investigate the influence of differentiation and coating of target substrate on the fundamental rolling characteristics of the cells under a constant pressing force which mimics the pressing force to the vessel wall by erythrocytes in vivo. METHODS: Motions of undifferentiated and differentiated HL-60 cells on plain or MPC-polymer-coated flat glass substrate were compared using a homemade inclined centrifuge microscope system. RESULTS: Most of the cells alternated between stop and go during the motion. The differentiation resulted in a high temporal ratio of the non-moving state and low mean velocity during the moving state, together with a high suppression performance of cell adhesion by the polymer. It was also suggested that the cells were mostly rolling but that the coating probably induced an infrequent slip on the substrate to stabilize the cells motion. CONCLUSIONS: Differentiation strongly affects adhesivity of HL-60 cells but less affects the mean velocity. Our findings also demonstrate the importance of the pressing force and advantage of the present system with respect to classical flow chambers.

Photoplethysmography and ultrasonic-measurement-integrated simulation to clarify the relation between two-dimensional unsteady blood flow field and forward and backward waves in a carotid artery.

Understanding the spatiotemporal change in hemodynamics is essential for the basic research of atherosclerosis. The objective of this study was to establish a methodology to clarify the relation between a two-dimensional (2D) unsteady blood flow field and forward and backward propagating waves in a carotid artery. This study utilized photoplethysmography (PPG) for blood pressure measurement and two-dimensional ultrasonic-measurement-integrated (2D-UMI) simulation for flow field analysis. The validity of the methodology was confirmed in an experiment for a carotid artery of a healthy volunteer. Synchronization between the pressure measurement and flow field analysis was achieved with an error of <10 ms. A 2D unsteady blood flow field in the carotid artery was characterized in relation to forward and backward waves. 2D-UMI simulation reproduced the flow field in which the wall shear stress takes a maximum at the time of the backward wave superiority in the systolic phase, whereas 2D ordinary simulation failed to reproduce this feature because of poor reproducibility of velocity distribution. In conclusion, the proposed methodology using PPG and 2D-UMI simulation was shown to be a potential tool to clarify the relation between 2D unsteady blood flow field and the forward and backward waves in a carotid artery.

[Surgical Resection and Adjuvant Chemotherapy with FOLFOX6 for Primary Duodenal Adenocarcinoma and Nodal Metastasis Resulted in Complete Remission].

Primary duodenal adenocarcinoma is a rare disease, and cases with nodal metastases have a poor prognosis. A 46-year-old man complaining of bloody stool visited our hospital. Endoscopy, CT, and PET-CT showed adenocarcinoma in the 2nd portion of the duodenum. We performed radical resection (PpPD) and pathological findings showed T3N1M0 (Stage III). Chemotherapy consisting of FOLFOX6 was administered for 6 months after surgery. The patient was alive without recurrence 5 years later. This case suggests that adjuvant chemotherapy (FOLFOX regimen) following curative resection including lymph node removal is an effective treatment for cases with tumor involvement of the lymph nodes.

Numerical reproduction of hemodynamics change by acupuncture on Taichong (LR-3) based on the lumped-parameter approximation model of the systemic arteries.

BACKGROUND: The aim of this study was to develop a mathematical model of blood flow in the systemic circulation to emulate the change in hemodynamics by acupuncture therapy to elucidate the mechanism of the therapy. For this purpose, as a first step, a simple model of arterial blood flow was presented to reproduce previously reported change in the blood flow volume by the acupuncture needle stimulation of Taichong (LR-3). METHODS: This model was based on the lumped-parameter approximation of arterial blood flow together with linear resistance of peripheral circulation. It has been reported that blood flow in the left arm was enhanced after the stimulation, yielding the peripheral vascular resistance-regulated blood flow dominated by the sympathetic nervous system. In addition to the peripheral resistance, another parameter that possibly regulates the blood flow is the cross-sectional area of the vessel. These two factors were changed to numerically examine their contributions to the blood flow based on the hypothesis that they could be changed by the stimulation. The numerical result was compared with the experimental result to confirm the validity of the hypothesis that the blood flow in the arm is regulated by the peripheral resistance. RESULTS: This model is extremely simple and the physical parameters introduced for the simulation were gleaned from different reports in the literature. It was demonstrated, however, that regulation of the peripheral resistance rather than of the cross-sectional area could reproduce the experimentally observed change in the blood flow. Moreover, the relationship between the changes in the flow volume and the systemic vascular resistance quantitatively matched the experimental data. CONCLUSION: The present model has a potential to emulate hemodynamic change by acupuncture therapy by incorporating physiological correlation of stimulation of an acupoint and regulation of parameters that affect the hemodynamics.

Numerical analysis for elucidation of nonlinear frictional characteristics of a deformed erythrocyte moving on a plate in medium subject to inclined centrifugal force.

Complex interactions between blood cells, plasma proteins, and glycocalyx in the endothelial surface layer are crucial in microcirculation. To obtain measurement data of such interactions, we have previously performed experiments using an inclined centrifuge microscope, which revealed that the nonlinear velocity-friction characteristics of erythrocytes moving on an endothelia-cultured glass plate in medium under inclined centrifugal force are much larger than those on plain or material-coated glass plates. The purpose of this study was to elucidate the nonlinear frictional characteristics of an erythrocyte on plain or material-coated glass plates as the basis to clarify the interaction between the erythrocyte and the endothelial cells. We propose a model in which steady motion of the cell is realized as an equilibrium state of the force and moment due to inclined centrifugal force and hydrodynamic flow force acting on the cell. Other electrochemical effects on the surfaces of the erythrocyte and the plate are ignored for the sake of simplicity. Numerical analysis was performed for a three-dimensional flow of a mixture of plasma and saline around a rigid erythrocyte model of an undeformed biconcave shape and a deformed shape with a concave top surface and a flat bottom surface. A variety of conditions for the concentration of plasma in a medium, the velocity of the cell, and the minimum gap width and the angle of attack of the cell from the plate, were examined to obtain the equilibrium states. A simple flat plate model based on the lubrication theory was also examined to elucidate the physical meaning of the model. The equilibrium angle of attack was obtained only for the deformed cell model and was represented as a power function of the minimum gap width. A simple flat plate model qualitatively explains the power function relation of the frictional characteristics, but it cannot explain the equilibrium relation, confirming the computational result that the deformation of the cell is necessary for the equilibrium. The frictional characteristics obtained from the present computation qualitatively agree with those of former experiments, showing the validity of the proposed model.

Simultaneous analysis system for blood pressure and flow using photoplethysmography and ultrasonic-measurement-integrated simulation.

We developed a simultaneous analysis system for blood pressure and flow using photoplethysmography and ultrasonic-measurement-integrated simulation. The validity of the system was confirmed by analysis of blood flow field in a carotid artery and corresponding wave intensity (WI) values.

Numerical simulation of passage of a neutrophil through a rectangular channel with a moderate constriction.

The authors have previously presented a mathematical model to predict transit time of a neutrophil through an alveolar capillary segment which was modeled as an axisymmetric arc-shaped constriction settled in a cylindrical straight pipe to investigate the influence of entrance curvature of a capillary on passage of the cell. The axially asymmetric cross section of a capillary also influences the transit time because it requires three-dimensional deformation of a cell when it passes through the capillary and could lead to plasma leakage between the cell surface and the capillary wall. In this study, a rectangular channel was introduced, the side walls of which were moderately constricted, as a representative of axially asymmetric capillaries. Dependence of transit time of a neutrophil passing through the constriction on the constriction geometry, i.e., channel height, throat width and curvature radius of the constriction, was numerically investigated, the transit time being compared with that through the axisymmetric model. It was found that the transit time is dominated by the throat hydraulic diameter and curvature radius of the constriction and that the throat aspect ratio little affects the transit time with a certain limitation, indicating that if an appropriate curvature radius is chosen, such a rectangular channel model can be substituted for an axisymmetric capillary model having the same throat hydraulic diameter in terms of the transit time by choosing an appropriate curvature radius. Thus, microchannels fabricated by the photolithography technique, whose cross section is generally rectangular, are expected to be applicable to in vitro model experiments of neutrophil retention and passage in the alveolar capillaries.

7Li NMR studies on complexation reactions of lithium ion with cryptand C211 in ionic liquids: comparison with corresponding reactions in nonaqueous solvents.

(7)Li NMR spectra of DEME-TFSA [DEME=N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium; TFSA=bis(trifluoromethanesulfonyl)amide], EMI-TFSA (EMI=1-ethyl-3-methylimidazolium), MPP-TFSA (MPP = N-methyl-N-propylpyridinium), DEME-PFSA [PFSA=bis(pentafluoroethanesulfonyl)amide], and DEME-HFSA [HFSA=bis(heptafluoropropanesulfonyl)amide] ionic liquid (IL) solutions containing LiX (X=TFSA, PFSA, or HFSA) and C211 (4,7,13,18-tetraoxa-1,10-diazabicyclo[8.5.5]eicosane) were measured at various temperatures. As a result, it was found that the uncomplexed Li(I) species existing as [Li(X)(2)](-) in the present ILs exchange with the complexed Li(I) ([Li·C211](+)) and that the exchange reactions proceed through the bimolecular mechanism, [Li·C211](+) + [*Li(X)(2)](-)=[*Li·C211](+) + [Li(X)(2)](-). Kinetic parameters [k(s)/(kg m(-1) s(-1)) at 25 °C, ΔH(++)/(kJ mol(-1)), ΔS(++)/(J K(-1) mol(-1))] are as follows: 5.57×10(-2), 69.8 ± 0.4, and -34.9 ± 1.0 for the DEME-TFSA system; 5.77×10(-2), 70.6 ± 0.2, and -31.9 ± 0.6 for the EMI-TFSA system, 6.13×10(-2), 69.0 ± 0.3, and -36.7 ± 0.7 for the MPP-TFSA system; 1.35 × 10(-1), 65.2 ± 0.5, and -43.1 ± 1.4 for the DEME-PFSA system; 1.14×10(-1), 64.4 ± 0.3, and -47.1 ± 0.6 for the DEME-HFSA system. To compare these kinetic data with those in conventional nonaqueous solvents, the exchange reactions of Li(I) between [Li·C211](+) and solvated Li(I) in N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) were also examined. These Li(I) exchange reactions were found to be independent of the concentrations of the solvated Li(I) and hence proposed to proceed through the dissociative mechanism. Kinetic parameters [k(s)/s(-1) at 25 °C, ΔH(++)/(kJ mol(-1)), ΔS(++)/(J K(-1) mol(-1))] are as follows: 1.10 × 10(-2), 68.9 ± 0.2, and -51.3 ± 0.4 for the DMF system; 1.13×10(-2), 76.3 ± 0.3, and -26.3 ± 0.8 for the DMSO system. The differences in reactivities between ILs and nonaqueous solvents were proposed to be attributed to those in the chemical forms of the uncomplexed Li(I) species, i.e., the negatively charged species ([Li(X)(2)](-)) in ILs, and the positively charged ones ([Li(solvent)(n)](+)) in nonaqueous solvents.

Senile systemic amyloidosis in an aged savannah monkey (Cercopithecus aethiops) with tenosynovial degeneration.

Senile systemic amyloidosis (SSA) is a rather common disease in elderly people, but it is very rare in animals, including nonhuman primates. Pathological examination of a 26-year-old male savannah monkey (Cercopithecus aethiops) revealed systemic amyloidosis with severe cardiac fibrosis, and tenosynovial degeneration of the elbow and knee joints. The amyloid deposits were observed predominantly in the heart, lung, intestine and tenosynovium, and were positive for transthyretin (TTR) in immunohistochemistry. Immunohistochemical results, together with the distribution of the amyloid deposited lesions and the age of the monkey, were equivalent to those of human SSA. This is the second case of animal SSA with unprecedented TTR amyloid deposited lesions of the tenosynovium resembling human SSA. There may be a genetic factor that makes this species susceptible to SSA, since SSA has been reported in no other mammal besides humans.

Numerical simulation of distribution of neutrophils in a lattice alveolar capillary network.

Neutrophils are known to be retained in narrow pulmonary capillaries, even in normal lungs, due to their low deformability, resulting in a higher concentration than that in systemic circulation. In this study, to obtain a fundamental understanding of the behavior of neutrophils, we simplified an alveolar capillary network to a rectangular grid of short capillary segments and numerically investigated the flow of a suspension of neutrophils and plasma through the capillary network for various concentrations of the suspension, Csus, injected into the network. The cells traveled limited preferential paths in the network while Csus was low. Retention of a cell or cells induced plugging of the segment with a cessation of blood flow, and as the result of the changed plasma flow field caused by such plugging, the cells took various routes differing from the preferential paths. A low incidence of plugging helped to accelerate the cells flowing in the network with tight segments, resulting in a decrease in their mean transit time through the network as compared with the case of a single-cell transit. On the contrary, however, an increasing incidence of plugging induced backward motion of the cells and a resultant increase in the mean transit time. The time-averaged number of cells in the network increased with the increase in Csus, and the fractional residence time of cells in individual segments approached a constant. This means that a high concentration of neutrophils facilitates their uniform distribution in the network. However, the ratio between the time-averaged concentration of the cells in the network and Csus decreased and our numerical simulation did not reach the experimentally obtained value. This implies that, in a real alveolar capillary bed, plasma leaks through the plugged segments or that the capillary network has bypasses through which the plasma can flow.

Frictional characteristics of erythrocytes on coated glass plates subject to inclined centrifugal forces.

In recent years a diamond-like carbon (DLC) film and a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer have attracted attention as coating materials for implantable artificial organs or devices. When these materials are coated on vascular devices, compatibility to blood is an important problem. The present paper focuses on friction characteristics of erythrocytes to these coating materials in a medium. With an inclined centrifuge microscope developed by the authors, observation was made for erythrocytes moving on flat glass plates with and without coating in a medium of plasma or saline under the effect of inclined centrifugal force. Friction characteristics of erythrocytes with respect to these coating materials were then measured and compared to each other to characterize DLC and MPC as coating materials. The friction characteristics of erythrocytes in plasma using the DLC-coated and noncoated glass plates are similar, changing approximately proportional to the 0.5th power of the cell velocity. The cells stick to these plates in saline as well, implying the influence of plasma protein. The results using the MPC-coated plate in plasma are similar to those of the other plates for large cell velocities, but deviate from the other results with decreased cell velocity. The results change nearly proportional to the 0.75th power of the cell velocity in the range of small velocities. The results for the MPC-coated plate in saline are similar to that in plasma but somewhat smaller, implying that the friction characteristics for the MPC-coated plate are essentially independent of plasma protein.

Solvation of lithium ion in N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)-amide using Raman and multinuclear NMR spectroscopy.

The solvation structure of the Li(I) species in N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethane-sulfonyl) amide (DEMETFSA) was studied by measuring the Raman and multinuclear NMR spectra of DEMETFSA solutions containing LiTFSA of various concentrations (0.12-1.92 mol kg(-1), [TFSA(-)]/[Li(I)] = 20.0-2.22). It was found from Raman spectra that an intense band due to the free TFSA(-) anion at around 741 cm(-1) becomes weak, and a new band appears at around 747 cm(-1) with an increase in the concentrations of LiTFSA, and that the pseudoisosbestic point is observed at around 744 cm(-1) in the range of [TFSA(-)]/[Li(I)] = 20.0-5.00. From analyses of these Raman bands, the number of TFSA(-) anions bound to the Li(+) ion was evaluated to be 1.85 +/- 0.08, and hence, the Li(I) in DEMETFSA solutions was proposed to exist as [Li(TFSA)(2)](-) in the range of [TFSA(-)]/[Li(I)] = 20.0-5.00. Furthermore, in the range of [TFSA(-)]/[Li(I)] = 2.86-2.22, the band observed at around 747 cm(-1) became more strong, and the pseudoisosbestic point disappeared. From these phenomena, it seems that the Li(I) oligomer species are formed in the higher concentration region of LiTFSA. The (19)F NMR signal of the TFSA(-) anion observed at 42.31 ppm in neat DEMETFSA was found to shift to a higher field linearly with an increase in the concentrations of LiTFSA ([LiTFSA] = 0.00-0.99 mol kg(-1), [TFSA(-)]/[Li(+)] = 20.0-3.33), while in a higher concentration range ([LiTFSA] > or = 1.26 mol kg(-1), [TFSA(-)]/[Li(+)] < or = 2.86), a slight deviation from linearity was observed. On the other hand, the (7)Li NMR signal did not show an appreciable shift with increasing LiTFSA concentrations. These results support that the Li(I) species in DEMETFSA solutions exist as [Li(TFSA)(2)](-) and the Li(I) oligomer species in the low and high concentration regions of LiTFSA, respectively.

Modeling neutrophil transport in pulmonary capillaries.

Neutrophils can be retained in the pulmonary microvasculature due to their low deformability, resulting in having a higher concentration there than in the systemic circulation, even in normal lungs. It is thought that this high concentration of the cells facilitates their effective recruitment to sites of inflammation. Thus, in order to understand their role in the immune system in the lungs, where blood comes in contact with outer air via thin septa of alveoli, it is important to clarify their flow characteristics in the pulmonary capillary bed. However, in contrast to erythrocytes in systemic capillaries, little research has been performed on the flow of neutrophils in pulmonary capillaries. This may be partly because no complete rheological model of the cell has been established yet, and partly because pulmonary capillaries are very short and closely interconnected, forming a complicated three-dimensional network, in addition to difficulty in in vivo experimental observations. Moreover, the neutrophils change their mechanical properties and show active motion in response to some chemoattractants. In this article, various proposed rheological models of the neutrophil, flow models of a cell through a single capillary segment, and alveolar capillary network models are introduced, aiming at the numerical simulation of neutrophil transport in the pulmonary microvasculature.

Total synthesis of (-)-martinellic acid via radical addition-cyclization-elimination reaction.

The asymmetric total synthesis of martinellic acid, the first pyrrolo[3,2-c]quinoline alkaloid found in nature, is described. Three key steps in our synthesis of (-)-martinellic acid are the Bu(3)SnH-promoted radical addition-cyclization-elimination (RACE) reaction of an oxime ether with an alpha,beta-unsaturated ester to generate the pyrrolo[3,2-c]quinoline core, a chemoselective lactam carbonyl reduction, and guanidinylation under Mitsunobu reaction conditions. The key radical cyclization has also been investigated by using SmI(2). (-)-Martinellic acid was synthesized from commercially available methyl 4-bromo-3-methylbenzoate in fewer steps than previous syntheses and in an improved overall yield.

Numerical simulation of flow for viscoelastic neutrophil models in a rectangular capillary network: effects of capillary shape and cell stiffness on transit time.

The concentration of neutrophils in the pulmonary microvasculature is higher than in large systemic vessels. It is thought that the high concentration of neutrophils facilitates their effective recruitment to sites of inflammation. Thus, in order to understand the role of neutrophils in the immune system, it is important to clarify their flow characteristics in the pulmonary microvasculature. In a previous study, we developed a model to simulate the flow of neutrophils in a capillary network, in which the cells were modeled as spheres of a Maxwell material with a cortical tension and the capillary segments were modeled as arc-shaped constrictions in straight pipes. In the present paper, the flow of neutrophils in a simplified alveolar capillary network model is investigated for various constriction shapes and cell stiffnesses. Finally, it is shown that both the coefficient of variation of the transit time of the cells, which is the standard deviation divided by the mean transit time, and the mean transit time increase as the capillary segments become steep or tight, or when the cells become hard. The mean value of the transit time exceeds the median for all of the conditions that occur in real lungs, although the difference between them is small.

Numerical simulation of noninvasive blood pressure measurement.

In this paper, a simulation model based on the partially pressurized collapsible tube model for reproducing noninvasive blood pressure measurement is presented. The model consists of a collapsible tube, which models the pressurized part of the artery, rigid pipes connected to the collapsible tube, which model proximal and distal region far from the pressurized part, and the Windkessel model, which represents the capacitance and the resistance of the distal part of the circulation. The blood flow is simplified to a one-dimensional system. Collapse and expansion of the tube is represented by the change in the cross-sectional area of the tube considering the force balance acting on the tube membrane in the direction normal to the tube axis. They are solved using the Runge-Kutta method. This simple model can easily reproduce the oscillation of inner fluid and corresponding tube collapse typical for the Korotkoff sounds generated by the cuff pressure. The numerical result is compared with the experiment and shows good agreement.

[The use experience of enteral nutrition pump (Applix Smart)].

Nutritional management by using enteral feeding method of nutrition is required for patients of gastroenterological disease with functional disorder in digestion-absorption, and for cases where the patients have difficulty in taking food orally. There are many cases where enteral nutrition pumps are used for administration of nutritious medicines. Approximately 150 enteral nutrition pumps (including house use and home rental) have currently been utilized at our facility. The department of ME Center takes care of enteral nutrition pumps for maintenance and control. On the other hand, we needed to conduct a study for a new pump in replacing Frenta System IV due to the pump was no longer available. At this presentation, we are introducing a new pump manufactured by Fresenius as a replacement of the Frenta System IV. In the meantime, we would like to report a comparison examination of the pump based on its functionality, performance and user friendliness from the view from a clinical technologist as well.

Simulation model for flow of neutrophils in pulmonary capillary network.

The concentration of neutrophils in the pulmonary microvasculature is higher than in systemic large vessels. It is thought that the high concentration of neutrophils facilitates their effective recruitment to sites of inflammation. Thus, in order to understand the role of neutrophils in the immune system, it is important to clarify their flow characteristics in the pulmonary microvasculature. In previous studies, we numerically investigated the motion of a neutrophil through a single capillary segment modeled by a moderate axisymmetric constriction in a straight pipe, developing a mathematical model for the prediction of the transit time of the cell through the segment. In the present study, this model was extended for application to network simulation of the motion of neutrophils. First, we numerically investigated shape recovery of a neutrophil after expulsion from a narrow capillary segment. This process was modeled in two different phases: elastic recovery and viscous recovery. The resulting model was combined with the previously developed models to simulate motion of the cells and plasma flow in a capillary network. A numerical simulation of the motion of neutrophils and plasma flow in a simple lattice capillary network showed that neutrophils were widely dispersed in the network with an increased concentration.

Fundamental study of ultrasonic-measurement-integrated simulation of real blood flow in the aorta.

Acquisition of detailed information on the velocity and pressure fields of the blood flow is essential to achieve accurate diagnosis or treatment for serious circulatory diseases such as aortic aneurysms. A possible way to obtain such information is integration of numerical simulation and color Doppler ultrasonography in the framework of a flow observer. This methodology, namely, Ultrasonic-Measurement-Integrated (UMI) Simulation, consists of the following processes. At each time step of numerical simulation, the difference between the measurable output signal and the signal indicated by numerical simulation is evaluated. Feedback signals are generated from the difference, and numerical simulation is updated applying the feedback signal to compensate for the difference. This paper deals with a numerical study on the fundamental characteristics of UMI simulation using a simple two-dimensional model problem for the blood flow in an aorta with an aneurysm. The effect of the number of feedback points and the feedback formula are investigated systematically. It is revealed that the result of UMI simulation in the feedback domain rapidly converges to the standard solution, even with usually inevitable incorrect upstream boundary conditions. Finally, an example of UMI simulation with feedback from real color Doppler measurement also shows a good agreement with measurement.

Neutrophil transit times through pulmonary capillaries: the effects of capillary geometry and fMLP-stimulation.

The deformations of neutrophils as they pass through the pulmonary microcirculation affect their transit time, their tendency to contact and interact with the endothelial surface, and potentially their degree of activation. Here we model the cell as a viscoelastic Maxwell material bounded by constant surface tension and simulate indentation experiments to quantify the effects of (N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-stimulation on its mechanical properties (elastic shear modulus and viscosity). We then simulate neutrophil transit through individual pulmonary capillary segments to determine the relative effects of capillary geometry and fMLP-stimulation on transit time. Indentation results indicate that neutrophil viscosity and shear modulus increase by factors of 3.4, for 10(-9) M fMLP, and 7.3, for 10(-6) M fMLP, over nonstimulated cell values, determined to be 30.8 Pa.s and 185 Pa, respectively. Capillary flow results indicate that capillary entrance radius of curvature has a significant effect on cell transit time, in addition to minimum capillary radius and neutrophil stimulation level. The relative effects of capillary geometry and fMLP on neutrophil transit time are presented as a simple dimensionless expression and their physiological significance is discussed.