豚鼠高脂血症模型的建立及机制探讨

目的建立豚鼠高脂血症模型,探讨模型形成机制并与大鼠模型进行比较。方法豚鼠模型和大鼠模型1组用低胆固醇（0.1%）饲料诱导,大鼠模型2组用高胆固醇（1%）饲料诱导,连续诱导4周。第3、4周分别取血测定血清脂质水平及CETP表达,4周末剖取肝脏检测肝脏FC、TG、ACAT、CYP7A1等指标。动态观察两种动物形成高脂血症状况。结果与对照组比较,豚鼠模型组于第3周血清TC、LDL-C、TG分别升高3.92倍、3.75倍和1.24倍,4周末血清CETP表达、肝脏ACAT活性明显增加,但肝CYP7A1水平变化不大。大鼠模型1组经低胆固醇饲料诱导4周,血脂水平变化不明显,模型2组经高胆固醇饲料诱导于第3周血清TC、LDL-C分别升高1.24倍和1.54倍,明显低于同期豚鼠模型组,4周末大鼠两个模型组肝CYP7A1活性显著增强,血清TG、CETP水平、肝ACAT活性均未见明显变化。结论豚鼠对高脂饲料较大鼠敏感,是一种比大鼠更理想的高血脂模型动物,模型形成机制与血清CETP表达、肝ACAT及CYP7A1活性变化密切相关。     

Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke

Variations in apparent diffusion coefficient of water (ADC) and blood-brain barrier (BBB) permeability after ischemia have been suggested, though the correlation between ADC alterations and BBB opening remains to be studied. We hypothesized that there are correlations between the alteration of ADC and BBB permeability. Rats were subjected to 2 h of transient middle cerebral artery occlusion and studied at 3 and 48 h of reperfusion, which are crucial times of BBB opening. BBB permeability and ADC values were measured by dynamic contrast-enhanced MRI and diffusion-weighted imaging, respectively. Temporal and spatial analyses of the evolution of BBB permeability and ADC alteration in cortical and subcortical regions were conducted along with the correlation between ADC and BBB permeability data. We found significant increases in BBB leakage and reduction in ADC values between 3 and 48 h of reperfusion. We identified three MR tissue signature models: high K_i and low ADC, high K_i and normal ADC, and normal K_i and low ADC. Over time, areas with normal K_i and low ADC transformed into areas with high K_i. We observed a pattern of lesion evolution where the extent of initial ischemic injury reflected by ADC abnormalities determines vascular integrity. Our results suggest that regions with vasogenic edema alone are not likely to develop low ADC by 48 h and may undergo recovery.     

Spatiotemporal Phylogenetic Analysis and Molecular Characterisation of Infectious Bursal Disease Viruses Based on the VP2 Hyper-Variable Region

Background

Infectious bursal disease is a highly contagious and acute viral disease caused by the infectious bursal disease virus (IBDV); it affects all major poultry producing areas of the world. The current study was designed to rigorously measure the global phylogeographic dynamics of IBDV strains to gain insight into viral population expansion as well as the emergence, spread and pattern of the geographical structure of very virulent IBDV (vvIBDV) strains.

Methodology/Principal Findings

Sequences of the hyper-variable region of the VP2 (HVR-VP2) gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank database; Cuban sequences were obtained in the current work. All sequences were analysed by Bayesian phylogeographic analysis, implemented in the Bayesian Evolutionary Analysis Sampling Trees (BEAST), Bayesian Tip-association Significance testing (BaTS) and Spatial Phylogenetic Reconstruction of Evolutionary Dynamics (SPREAD) software packages. Selection pressure on the HVR-VP2 was also assessed. The phylogeographic association-trait analysis showed that viruses sampled from individual countries tend to cluster together, suggesting a geographic pattern for IBDV strains. Spatial analysis from this study revealed that strains carrying sequences that were linked to increased virulence of IBDV appeared in Iran in 1981 and spread to Western Europe (Belgium) in 1987, Africa (Egypt) around 1990, East Asia (China and Japan) in 1993, the Caribbean Region (Cuba) by 1995 and South America (Brazil) around 2000. Selection pressure analysis showed that several codons in the HVR-VP2 region were under purifying selection.

Conclusions/Significance

To our knowledge, this work is the first study applying the Bayesian phylogeographic reconstruction approach to analyse the emergence and spread of vvIBDV strains worldwide.     

Prolonged Mechanical Ventilation Alters the Expression Pattern of Angio-neogenetic Factors in a Pre-Clinical Rat Model

Objective

Mechanical ventilation (MV) is a life saving intervention for patients with respiratory failure. Even after 6 hours of MV, diaphragm atrophy and dysfunction (collectively referred to as ventilator-induced diaphragmatic dysfunction, VIDD) occurs in concert with a blunted blood flow and oxygen delivery. The regulation of hypoxia sensitive factors (i.e. hypoxia inducible factor 1α, 2α (HIF-1α,–2α), vascular endothelial growth factor (VEGF)) and angio-neogenetic factors (angiopoietin 1–3, Ang) might contribute to reactive and compensatory alterations in diaphragm muscle.

Methods

Male Wistar rats (n = 8) were ventilated for 24 hours or directly sacrificed (n = 8), diaphragm and mixed gastrocnemius muscle tissue was removed. Quantitative real time PCR and western blot analyses were performed to detect changes in angio-neogenetic factors and inflammatory markers. Tissues were stained using Isolectin (IB 4) to determine capillarity and calculate the capillary/fiber ratio.

Results

MV resulted in up-regulation of Ang 2 and HIF-1α mRNA in both diaphragm and gastrocnemius, while VEGF mRNA was down-regulated in both tissues. HIF-2α mRNA was reduced in both tissues, while GLUT 4 mRNA was increased in gastrocnemius and reduced in diaphragm samples. Protein levels of VEGF, HIF-1α, -2α and 4 did not change significantly. Additionally, inflammatory cytokine mRNA (Interleukin (IL)-6, IL-1β and TNF α) were elevated in diaphragm tissue.

Conclusion

The results demonstrate that 24 hrs of MV and the associated limb disuse induce an up-regulation of angio-neogenetic factors that are connected to HIF-1α. Changes in HIF-1α expression may be due to several interactions occurring during MV.     

Characterisation and Molecular Identification of Adrenomedullin Binding Sites in the Rat Spinal Cord: A Comparison with Calcitonin Gene-Related Peptide Receptors

Abstract: Calcitonin gene-related peptide (CGRP) and its receptors are found in mammalian spinal cord. We show, for the first time, binding sites for the novel related peptide adrenomedullin in rat spinal cord microsomes. ¹²⁵I-Adrenomedullin binding showed high affinity ( K _D = 0.45 ± 0.06 n M ) and sites were abundant ( B _max = 723 ± 71 fmol/mg of protein). CGRP, amylin, and calcitonin did not compete at these sites ( K _i > 10 µ M ). High-affinity CGRP binding sites ( K _D = 0.18 ± 0.01 n M ) were much less numerous ( B _max = 17.7 ± 2.4 fmol/mg of protein) and showed competition by unlabeled adrenomedullin ( K _i = 34.6 ± 2.4 n M ). Chemical cross-linking revealed a major band for ¹²⁵I-adrenomedullin of M_r = 84,400 ± 1,200 and a minor band of M_r = 122,000 ± 8,700. ¹²⁵I-CGRP cross-linking showed bands of lower molecular weight (M_r = 74,500 ± 5,000 and 61,000 ± 2,200). Enzymic deglycosylation of the adrenomedullin binding site showed a considerable carbohydrate content. Neither adrenomedullin nor CGRP was able to increase cyclic AMP in spinal cord. Adrenomedullin mRNA was present in spinal cord, at one-third of its level in lung, and adrenomedullin immunoreactivity was present, at a low concentration (40 fmol/g of tissue). Thus, the presence of abundant binding sites and adrenomedullin mRNA and immunoreactivity anticipate an as yet undefined function for this peptide in spinal cord.     

弱激光对大鼠胃运动的调节及其作用途径分析

采用成年Ｗｉｓｔａｒ雄性大鼠,应用Ｒａｙｂｏｕｌｄ法测定了弱激光照射足三里穴对大鼠胃运动的调节作用,实验结果为：（１）弱激光照射足三里穴对大鼠胃内压及胃收缩频率均有明显升高作用;（２）腹腔预先注射酚托拉明,部分抑制了弱激光效应;（３）腹腔预先注射心得安,显著地抑制了弱激光的升压及升频作用,并使胃内压及胃收缩频率低于单纯心得安的效应值;（４）腹腔预选注射纳洛酮,部分抑制了弱激光的效应;（５）腹腔预先     

Spatiotemporal Evolution of Ebola Virus Disease at Sub-National Level during the 2014 West Africa Epidemic: Model Scrutiny and Data Meagreness

Background

The Ebola outbreak in West Africa has infected at least 27,443 individuals and killed 11,207, based on data until 24 June, 2015, released by the World Health Organization (WHO). This outbreak has been characterised by extensive geographic spread across the affected countries Guinea, Liberia and Sierra Leone, and by localized hotspots within these countries. The rapid recognition and quantitative assessment of localised areas of higher transmission can inform the optimal deployment of public health resources.

Methods

A variety of mathematical models have been used to estimate the evolution of this epidemic, and some have pointed out the importance of the spatial heterogeneity apparent from incidence maps. However, little is known about the district-level transmission. Given that many response decisions are taken at sub-national level, the current study aimed to investigate the spatial heterogeneity by using a different modelling framework, built on publicly available data at district level. Furthermore, we assessed whether this model could quantify the effect of intervention measures and provide predictions at a local level to guide public health action. We used a two-stage modelling approach: a) a flexible spatiotemporal growth model across all affected districts and b) a deterministic SEIR compartmental model per district whenever deemed appropriate.

Findings

Our estimates show substantial differences in the evolution of the outbreak in the various regions of Guinea, Liberia and Sierra Leone, illustrating the importance of monitoring the outbreak at district level. We also provide an estimate of the time-dependent district-specific effective reproduction number, as a quantitative measure to compare transmission between different districts and give input for informed decisions on control measures and resource allocation. Prediction and assessing the impact of control measures proved to be difficult without more accurate data. In conclusion, this study provides us a useful tool at district level for public health, and illustrates the importance of collecting and sharing data.     

Local Dynamics During the Mixing of Saliva with a Model Colloidal Food

The events occurring during the spontaneous mixing of an okra mucilage-based model liquid food with saliva were recorded, with a focus on the local dynamics of colloidal particles contained therein. An okra mucilage containing fluorescent microsphere probes (assuming the role of model emulsion droplets), was brought into contact with reconstituted saliva on the welled slide of a confocal microscope. The movement of the probes at the saliva–mucilage interface and in the bulk mucilage has been recorded over periods of 60 min. Data have been obtained on the total mobility of individual model droplets, their diffusion coefficients, and the local viscosities, providing information on the dynamics of processes which occur during the oral processing of colloidal liquids. The role of osmotic pressure gradients on the spreading of the droplets into saliva is discussed in relation to the microrheology data.     

近端胃切除与全胃切除在治疗近端胃癌中的疗效比较

目的:观察近端胃切除和全胃切除对近端胃癌的疗效。方法:比较28例患有早期近端胃癌接受近端胃切除28例患者与100例患有早期近端胃癌接受全胃切除的患者,观察近端胃切除是否优于全胃切除。结果:两种治疗方法手术时间、术后并发症(包括吻合口瘘)没有差异。两组患者胃切除后的代谢变化结果相似,体重,血清血红蛋白以及血清总蛋白浓度变化相近。近端胃切除后腹泻(32%)和胃食管返流(28%)最为常见,而全胃切除后餐后腹胀(21%)最为常见。二者的术后5年生存率没有明显差别。结论:近端胃切除不会由于残余胃的生理优势而优于全胃切除术。     

胃动素对大鼠下丘脑胃牵张敏感神经元和胃运动的影响(英文)

目的:研究胃动素对下丘脑弓状核胃牵张敏感神经元放电活动和胃运动的影响。方法:采用4管玻璃微电极细胞外记录胃动素对大鼠弓状核胃牵张敏感神经元活动,采用胃内置传感器观察胃动素对对清醒大鼠胃运动的影响。结果:65.5%的弓状核神经元为胃扩张敏感性神经元,其中55.6%为胃扩张兴奋性神经元,44.4%为抑制性神经元。胃扩张刺激后兴奋性神经元的放电频率显著增加(P<0.01),而抑制性神经元的放电频率显著降低(P<0.01)。弓状核内微量注射胃动素,70%的兴奋性神经元在胃扩张刺激后表现为兴奋作用,17.5%的神经元表现为抑制作用,并且放电频率显著增加(P<0.05)。同样,在抑制性神经元中,65.6%在注射胃动素后引起电活动增强,放电频率显著降低(P<0.05)。而胃动素受体拮抗剂GM-109可以完全阻断这种由胃动素诱导的兴奋作用,提示,胃动素在弓状核通过其特异性受体调控神经元活动。在胃运动实验中,弓状核微量注射胃动素后,胃运动的收缩频率和幅度都显著增加(P<0.05);同时,这种兴奋作用也可被GM-109阻断。结论:研究证实了弓状核胃动素神经元接收来自胃感受器的外周躯体感觉传入神经的冲动,并通过某些下级核团通路发挥...     

Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model

Glioblastoma multiforme (GBM) is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI) data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient’s prognosis.     

Swimming Motility in a Longitudinal Collection of Clinical Isolates of Burkholderia cepacia Complex Bacteria from People with Cystic Fibrosis

Chronic bacterial lung infections in cystic fibrosis (CF) are the leading cause of morbidity and mortality. While a range of bacteria are known to be capable of establishing residence in the CF lung, only a small number have a clearly established link to deteriorating clinical status. The two bacteria with the clearest roles in CF lung disease are Pseudomonas aeruginosa and bacteria belonging to the Burkholderia cepacia complex (BCC). A number of common adaptations by P. aeruginosa strains to chronic lung infection in CF have been well described. Typically, initial isolates of P. aeruginosa are nonmucoid and display a range of putative virulence determinants. Upon establishment of chronic infection, subsequent isolates ultimately show a reduction in putative virulence determinants, including swimming motility, along with an acquisition of the mucoid phenotype and increased levels of antimicrobial resistance. Infections by BCC are marked by an unpredictable, but typically worse, clinical outcome. However, in contrast to P. aeruginosa infections in CF, studies describing adaptive changes in BCC bacterial phenotype during chronic lung infections are far more limited. To further enhance our understanding of chronic lung infections by BCC bacteria in CF, we assessed the swimming motility phenotype in 551 isolates of BCC bacteria from cystic fibrosis (CF) lung infections between 1981 and 2007. These data suggest that swimming motility is not typically lost by BCC during chronic infection, unlike as seen in P. aeruginosa infections. Furthermore, while we observed a statistically significant link between mucoidy and motility, we did not detect any link between motility phenotype and clinical outcome. These studies highlight the need for further work to understand the adaptive changes of BCC bacteria during chronic infection in the CF lung.     

Effects of Cardiac Myosin Binding Protein-C on Actin Motility Are Explained with a Drag-Activation-Competition Model

Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart disease, its role in muscle contraction is not well understood. A mechanism remains elusive partly because the protein can have multiple effects, such as dual biphasic activation and inhibition observed in actin motility assays. Here we develop a mathematical model for the interaction of cMyBP-C with the contractile proteins actin and myosin and the regulatory protein tropomyosin. We use this model to show that a drag-activation-competition mechanism accurately describes actin motility measurements, while models lacking either drag or competition do not. These results suggest that complex effects can arise simply from cMyBP-C binding to actin.     

Control and Modulation of Fluid Flow in the Rat Kidney

We have developed a mathematical model of the rat’s renal hemodynamics in the nephron level, and used that model to study flow control and signal transduction in the rat kidney. The model represents an afferent arteriole, glomerular filtration, and a segment of a short-loop nephron. The model afferent arteriole is myogenically active and represents smooth muscle membrane potential and electrical coupling. The myogenic mechanism is based on the assumption that the activity of nonselective cation channels is shifted by changes in transmural pressure, such that elevation in pressure induces vasoconstriction, which increases resistance to blood flow. From the afferent arteriole’s fluid delivery output, glomerular filtration rate is computed, based on conservation of plasma and plasma protein. Chloride concentration is then computed along the renal tubule based on solute conservation that represents water reabsorption along the proximal tubule and the water-permeable segment of the descending limb, and chloride fluxes driven by passive diffusion and active transport. The model’s autoregulatory response is predicted to maintain stable renal blood flow within a physiologic range of blood pressure values. Power spectra associated with time series predicted by the model reveal a prominent fundamental peak at ～165 mHz arising from the afferent arteriole’s spontaneous vasomotion. Periodic external forcings interact with vasomotion to introduce heterodynes into the power spectra, significantly increasing their complexity.     

Investigation of the Spatiotemporal Responses of Nanoparticles in Tumor Tissues with a Small-Scale Mathematical Model

The transport and accumulation of anticancer nanodrugs in tumor tissues are affected by many factors including particle properties, vascular density and leakiness, and interstitial diffusivity. It is important to understand the effects of these factors on the detailed drug distribution in the entire tumor for an effective treatment. In this study, we developed a small-scale mathematical model to systematically study the spatiotemporal responses and accumulative exposures of macromolecular carriers in localized tumor tissues. We chose various dextrans as model carriers and studied the effects of vascular density, permeability, diffusivity, and half-life of dextrans on their spatiotemporal concentration responses and accumulative exposure distribution to tumor cells. The relevant biological parameters were obtained from experimental results previously reported by the Dreher group. The area under concentration-time response curve (AUC) quantified the extent of tissue exposure to a drug and therefore was considered more reliable in assessing the extent of the overall drug exposure than individual concentrations. The results showed that 1) a small macromolecule can penetrate deep into the tumor interstitium and produce a uniform but low spatial distribution of AUC; 2) large macromolecules produce high AUC in the perivascular region, but low AUC in the distal region away from vessels; 3) medium-sized macromolecules produce a relatively uniform and high AUC in the tumor interstitium between two vessels; 4) enhancement of permeability can elevate the level of AUC, but have little effect on its uniformity while enhancement of diffusivity is able to raise the level of AUC and improve its uniformity; 5) a longer half-life can produce a deeper penetration and a higher level of AUC distribution. The numerical results indicate that a long half-life carrier in plasma and a high interstitial diffusivity are the key factors to produce a high and relatively uniform spatial AUC distribution in the interstitium.     

Characterisation and Distribution of Inositol Polyphosphate and Ryanodine Receptors in the Rat Brain

Abstract: The regional distribution of inositol 1,4,5-trisphosphate (InsP₃), inositol 1,3,4,5-tetrakisphosphate (InsP₄), and ryanodine binding sites has been characterised and compared in the rat brain using radioligand binding assays. Cortical [³H]InsP₃ binding indicated similar positional and stereospecificity as observed in other tissues, with 100-fold selectivity for lnsP₃ over InsP₄. Similarly, high-affinity [³²P]InsP₄ binding also showed a high degree of positional specificity, with a 1,000-fold selectivity for InsP₄ over InsP₃. Initial characterisation of [³H]ryanodine binding to cortical membranes demonstrated that specific binding was highly dependent on high salt and micromolar Ca²⁺ concentrations and inhibited by Ca²⁺ levels of >1 mM. [³H]-Ryanodine binding was also enhanced by β,γ-methylene-adenosine 5′-trisphosphate and caffeine and inhibited by magnesium and ruthenium red (K_i= 0.81 μM). However, dantrolene (300 μM) was ineffective on the binding. Therefore, although the results indicate a greater similarity to the binding properties of the Ca²⁺-induced Ca²⁺ release channel isoform present in skeletal, rather than cardiac, muscle, it does not appear to be identical. Detailed binding analysis of ryanodine and polyphosphate sites, with the exception of ruthenium red, indicated no interaction between binding sites. Ruthenium red markedly enhanced the binding of both [³H]InsP₃ and [³²P]InsP₄, an effect most probably due to nonspecific complex formation. Regional binding of InP₃, InsP₄, and ryanodine in the rat brain was of similar affinity for each ligand in each area, but the density profile for each ligand was clearly different. The highest density of InsP₃ sites was in the cerebellum, whereas the highest density of ryanodine sites was in the hippocampus. High-affinity InsP₄ sites showed less regional diversity, with highest densities in the cerebellum, cortex, and hippocampus. However, in each area studied the density of sites followed the order InsP₃ > InsP₄ > ryanodine.     

Down-Regulation of CRMP-1 in Patients with Epilepsy and a Rat Model

The Collapsin Response Mediator Protein-1 (CRMP-1) is a brain specific protein identified as a signaling molecule of Semaphorin-3A and act as axon repellent guidance factor in nervous system. Recent studies indicated that axon guidance molecules may play a role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. This study aimed to investigate expression pattern of CRMP-1 in epileptogenesis. Using double immunofluorescence labeling, immunohistochemistry and western blot analysis, we looked into the CRMP-1 expression in temporal neocortex from patients with temporal lobe epilepsy (TLE) and histological normal temporal neocortex from the controls. We also studied the expression pattern of CRMP-1 in hippocampus and adjacent cortex of a TLE rat model on 6, 24, 72 h, 1, 2 weeks, 1 month, and 2 months post-seizure, and from control rats. CRMP-1 was mainly expressed in the neuronal cytoplasm in the temporal lobe of intractable TLE patients, which was co-expressed with -2. CRMP-1 expression was downregulated in temporal neocortical of TLE patients. In addition, in pilocarpine-induced animal model of epilepsy, CRMP-1 dynamically decreased in a range of 2 months. Thus, our results indicate that CRMP-1 may be involved in the development of TLE.     

Distribution and Chromatographic Characterisation of Gastrin and Cholecystokinin in the Rat Central Nervous System

Abstract: Two tissue extraction techniques and two radioimmunoassays were used to study the distribution of gastrin and cholecystokinin in rat brain. Small amounts of gastrin were found in extracts of neurohypophysis, but in neither ice-cold 90% methanol nor in boiling water-acetic acid extracts of the other 33 brain areas studied. Cholecystokinin was found in equivalent amounts in both types of extract of 31 areas. The distribution was similar to that in previous studies. The components of cholecystokinin immunoreactivity were characterised in 10 rat CNS tissues using four tissue extraction methods in conjunction with gel filtration and ion-exchange chromatography. The results demonstrated that gastrins were present only in the neurohypophysis and that in all other rat CNS tissues the main molecular component was indistinguishable from the sulphated octapeptide of cholecystokinin. Minor immunoreactive components were observed in all types of extract of all tissues with the properties of the desulphated octapeptide and the C-terminal tetrapeptide amide, suggesting they are genuine tissue components, not extraction artefacts. Large molecular forms of cholecystokinin were not detected in any tissue. The results emphasise the necessity of using two or more extraction methods and two or more chromatography systems in such a study.     

A Computer Model of Spermatogenesis In the Rat; Correlation With Flow Cytometric Data Based On Autoradiographic Cell-Cycle Properties

Abstract. A computer model of rat spermatogenesis was created, based on autoradiographic studies of durations of the phases of the cell cycle (G₁, S, G₂ and mitotic phases) of each germ-cell type. With this model it is possible to predict and to gain insight into the changes of the DNA content occurring during the normal process of spermatogenesis. the relative proportions of haploid, diploid, S phase and tetraploid germ cells with increasing age of the rats were calculated. Calculated and actual experimental flow cytometry data were compared to test the accuracy of the model, and these show good agreement. the present work demonstrates that single-parameter DNA analysis of testicular cells is primarily a reflection of germ cells in the spermatocyte and spermatid stages of development, and of non-germ cells. the FCM single-parameter DNA analysis of testicular cells is relatively insensitive to changes in the stem cell and spermatogonial stages of germ-cell development.