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Time-course changes in the expression of Na, K-ATPase and the morphometry of mitochondrion-rich cells in gills of euryhaline tilapia (Oreochromis mossambicus) during freshwater acclimation.

Changes in expression of Na, K-ATPase (NKA) and morphometry of mitochondrion-rich (MR) cells in gills of tilapia were investigated on a 96-hr time course following transfer from seawater (SW) to fresh water (FW). A transient decline in plasma osmolality and Na+, Cl- concentrations occurred from 3 hrs onward. Gills responded to FW transfer by decreasing NKA activity as early as 3 hrs from transfer. This response was followed by a significant decrease in the NKA isoform alpha1-mRNA abundance, which was detected by real-time PCR at 6 hrs post transfer. Next, a decrease of alpha1-protein amounts were observed from 6 hrs until 24 hrs post transfer. Additionally, during the time course of FW transfer, modifications in number and size of subtypes of gill MR cells were observed although no significant difference was found in densities of all subtypes of MR cells. These modifications were found as early as 3 hrs, evident at 6 hrs (exhibition of 3 subtypes of MR cells), and mostly completed by 24 hrs post transfer. Such rapid responses (in 3 hrs) as concurrent changes in branchial NKA expression and modifications of MR cell subtypes are thought to improve the osmoregulatory capacity of tilapia in acclimation from hypertonic SW to hypotonic FW.

Acclimatization↗

Morphometry of Macaca mulatta forelimb. III. Moment arm of shoulder and elbow muscles.

The conversion of muscle activity into smooth, purposeful movement of the limb depends complexly on the morphometry of muscles and their mechanical action on the skeleton. Although nonhuman primates are common subjects in motor control experiments (Scott [2000] Can J Physiol Pharmacol 78:923-933), little information is available on the morphometric properties of their upper limbs. One key variable is muscle moment arm, or mechanical advantage, which defines how linear motion or force of a muscle is translated into angular motion or torque at a joint. This study reports moment arm values with respect to joint angle (flexion/extension) of 14 muscles spanning the shoulder and elbow in Macaca mulatta. The magnitude of moment arm values ranged widely across muscles. In some muscles mechanical advantage remained constant with joint angle, whereas the moment arm of others varied strongly. The angle (Theta(f)(o)) at which optimal fascicle length (L(f)(o)) occurred showed strong trends, where the elbow-spanning muscles had Theta(f)(o) values clustered at mid-flexion and the shoulder musculature Theta(f)(o) values tended to be grouped around the neutral joint angle of 0 degrees. Estimates of peak muscle torque for flexor and extensor muscle groups at each joint were surprisingly similar in both magnitude and dependency on joint angle. The present study, along with the previous two in this series (Cheng and Scott [2000] J Morphol 245:206-224; Singh et al. [2002] J Morphol 251:323-332), provides a comprehensive description of the morphology of the proximal portion of the limb suitable for the development of a musculoskeletal model of the M. mulatta upper limb.

Animals↗

Suboccipital muscles in the cat neck: morphometry and histochemistry of the rectus capitis muscle complex.

The morphometry, histochemistry, and biomechanical relationships of rectus capitis muscles were examined in adult cats. This family of muscles contained six members on the dorsal, ventral, and lateral aspects of the upper cervical vertebral column. Three dorsal muscles (rectus capitis posterior major, medius, and minor) formed a layered complex spanning from C1 and C2 to the skull. Rectus capitis posterior major was composed predominantly of fast fibers, but the other two deeper muscles contained progressively higher proportions of slow fibers. One ventral muscle, rectus capitis anterior major, was architecturally complex. It originated from several cervical vertebrae and appeared to be divided into two different heads. In contrast, rectus capitis anterior minor and rectus capitis lateralis were short, parallel-fibered muscles spanning between the skull and C1. The ventral muscles all had nonuniform distributions of muscle-fiber types in which fast fibers predominated. Dorsal and ventral muscle groupings usually had cross-sectional areas of 0.5 cm2 or more, reflecting a potential capacity to generate maximal tetanic force in excess of 9 N. Biomechanical analyses suggested that one muscle, rectus capitis lateralis, had its largest moment in lateral flexion, whereas the other muscles had large, posturally dependent moment arms appropriate for actions in flexion-extension. The observation that most rectus muscles have relatively large cross-sectional areas and high fast-fiber proportions suggests that the muscles may have important phasic as well as postural roles during head movement.

Animals↗

A comparison between the accuracy of voxel-based morphometry and hippocampal volumetry in Alzheimer's disease.

PURPOSE: To compare the accuracy of voxel-based morphometry (VBM) and region of interest (ROI)-based hippocampal volumetry to detect medial temporal lobe atrophy in Alzheimer's disease (AD). MATERIALS AND METHODS: A total of 27 AD patients (age 74 +/- 9 years; 22 women; Mini-Mental State Exam [MMSE] 21 +/- 4) and 25 controls (age 70 +/- 8; 16 women; MMSE 29 +/- 1) were studied. Accuracy of VBM to detect gray matter loss in those seven AD patients and 11 controls with similar ROI-based hippocampal measures and of ROI-based volumetry to detect gray matter loss in those four AD patients and five controls with similar VBM-based hippocampal measures was assessed. VBM was performed with statistical parametric mapping (SPM99). RESULTS: The area under the curve was 0.96 (95% C.I., 0.92-1.00) for VBM, 0.89 (95% C.I., 0.80-0.98) for ROI-based hippocampal measures, and 0.99 (95% C.I., 0.96-1.00) for both. In subjects with similar ROI-based hippocampal measures, VBM detected atrophy in AD patients at P < 0.0001, while in subjects with similar VBM-based hippocampal measure, volumetry was not significant (P = 0.11). Both measures independently contributed to discrimination (P = 0.004 and P = 0.032) in a logistic regression model. CONCLUSION: These results indicate that VBM is more accurate, but the combination of both methods provides the highest accuracy for detection of hippocampal atrophy in AD.

Aged↗

Three-dimensional confocal morphometry reveals structural changes in astrocyte morphology in situ.

Neuronal activity and many pathological states in the CNS are accompanied by transient astrocytic swelling, which affects excitability, extrasynaptic transmission, and neuron-glia interactions. By using three-dimensional confocal morphometry (3DCM), we quantified the morphometric parameters of astrocytes in intact tissue. In experiments performed in brain cortex slices from transgenic GFAP/EGFP mice, we applied 3DCM to study the dynamic changes in astrocyte morphology during hypotonic stress. Our morphometric analysis showed that the effect of a 10-min application of hypotonic solution (200 mmol/kg) on the swelling of different cell compartments was dependent on the extent of the swelling of the total astrocyte volume. If the swelling of the whole cell, i.e., soma and processes, was less than approximately 10%, there were no differences between the swelling of the soma and the processes. However, if the swelling of the total cell volume was greater than 10%, the swelling of the processes was greater than the swelling of the soma. Analyzing the effect of hypotonic solution on the morphology of these astrocytes revealed that the total cell volume increased; however, certain cell compartments were distinguished in which the volume increased, whereas in other compartments cell volume decreased or apparently did not change, and the structure of some compartments was altered. Our data show that astrocytes in brain slices undergoing hypotonic stress display cell volume regulation as well as transient changes in morphology.

Animals↗

Correlates between nuclear magnetic resonance spectroscopy, diffusion weighted imaging, and CA1 morphometry following chronic brain ischemia.

Chronic brain ischemia (CBI) was induced in aging (13 month) rats by ligating the left subclavian artery and placing temporary occluders in each common carotid artery [three-vessel occlusion (3-VO)]. Carotid artery occluders were removed after 1, 2, or 3 weeks following brain ischemia or maintained for 9 weeks. Two rats were kept with their occluders in place for 25 weeks. On weeks 3 and 9 after CBI, 31P-/1H-nuclear magnetic resonance (NMR) spectroscopy and high resolution diffusion weighted imaging were performed in vivo, non-invasively for detection of hippocampal high energy phosphates, lactate, intracellular pH, N-acetyl-aspartate, choline, glutamate, creatine, and structural alterations of the brain following CBI. Brains were histologically processed for morphometry of glial fibrillary acidic protein (GFAP) and CA1 damaged neurons 9 weeks after CBI. 31P-/1H-NMR spectroscopy showed that high energy substrates remained normal in ischemic animals when compared to non-ischemic controls except for an elevation of phosphomonesters in the hippocampal region. Rats deoccluded 1 and 2 weeks after initiation of CBI had no NMR spectroscopic or imaging changes. Rats kept ischemic for 9 weeks showed high signal intensities in the parietal cortex detected by diffusion weighted imaging as well as CA1 damage and increased GFAP density but no cortical atrophy or neuronal damage could be detected histologically. Rats kept ischemic for 25 weeks showed extensive cortical atrophy which corresponded to the high signal intensity observed with diffusion weighted imaging in the group kept ischemic for 9 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.

Aged↗

Cortical atrophy in the cerebellar variant of multiple system atrophy: a voxel-based morphometry study.

This study aimed to determine in vivo the atrophy patterns in clinically established cerebellar variant of multiple-system atrophy (MSA-C) using voxel-based morphometry (VBM). Thirteen patients with MSA-C (12 probable, 1 possible) and 13 healthy controls matched for age and sex were included. High-resolution MR images were acquired with a 1.5 T scanner. Images were normalized onto a study-specific template, segmented into the tissue compartments, modulated with the Jacobian determinants, and finally smoothed with a Gaussian kernel filter of 10 mm. The general linear model was used to assess statistical differences in gray and white matter. Infratentorial atrophy was observed in the cerebellar hemispheres, vermis, mesencephalon, and pons of MSA-C patients. Supratentorial volume loss was found in orbitofrontal and mid-frontal regions as well as in temporomesial and insular areas of both hemispheres. A negative correlation was observed between a cerebellar ataxia score and the volume of cerebellar hemispheres, peduncles, and pons. To compare this atrophy pattern to that of spinocerebellar ataxia (SCA2), which was previously reported by our group, a conjunction analysis was assessed. We observed a volume loss shared by both disorders comprising the cerebellum, vermis, pons, mesencephalon, orbitofrontal, mid-frontal, and temporomesial cortex of both hemispheres as well as the left insular cortex.

Adult↗

Head of the caudate nucleus is most vulnerable in chorea-acanthocytosis: a voxel-based morphometry study.

Chorea-acanthocytosis (ChAc; OMIM 200150) is a rare autosomal recessive disease with dysfunction of the erythrocyte membrane, presenting with acanthocytes and neurological manifestations characterized by progressive hyperkinesias (chorea, dystonia) and neuropsychological impairment. Damage to the basal ganglia was described previously in neuropathological and neuroimaging investigations. We analyzed high-resolution MRI of six ChAc patients with mutations in the VPS13A gene (median age, 37 years; mean time since clinical onset, 13 years) with respect to regional atrophy by use of the observer-independent technique of voxel-based morphometry in comparison to 15 age-matched healthy controls. Additionally, global brain atrophy was determined using the standardized brain parenchymal fraction (BPF) method. A robust regional reduction of gray matter density was observed in the head of the caudate nucleus bilaterally and was nearly symmetrical (P < 0.001, corrected for small volumes). No additional gray matter changes were found. In the BPF analysis, there was no significant global brain atrophy. The predilection of atrophy in the head of the caudate nucleus, as suggested by our results, argues for a particular vulnerability of this part of the striatum in ChAc and is in agreement with pronounced neuropsychological disturbances that are thought to rely on these regions.

Adult↗

Fiber type morphometry and capillary geometry in free, vascularized muscle transfers.

In order to establish the relationship among intraoperative ischemia time, the recovery of contractile function, muscle fiber morphometry, and capillary geometry following free muscle transfer, 15 male dogs underwent unilateral, orthotopic free transfer of the left gracilis muscle with microneurovascular anastomosis. Intraoperative ischemia time varied from 0 to 4 hours. After a recovery period averaging 14 months, isometric contractile function was measured in the transfers and the contralateral, control muscles. Muscle fiber type composition, fiber size, and capillary geometry were quantified from histochemical sections. Transferred and control muscles had similar type I fiber percentages, type I fiber sizes, and capillary densities. Type II fiber sizes were reduced in transfers relative to controls. There was no significant effect of intraoperative ischemia on any morphometric variable. Although contractile function was generally reduced after free, vascularized transfer, there was only a weak correlation between the recovery of tetanic tension and type I fiber percentage (r = 0.53, P less than 0.05). It is concluded that free, vascularized muscle transfer results in minimal disturbance of muscle fiber type composition, fiber size, or capillary supply and that the diminished contractile function observed in this setting is still largely unexplained.

Analysis of Variance↗

The use of nuclear morphometry to predict prognosis in pediatric urologic malignancies: a review.

Wilms tumor, the most common pediatric urologic malignancy, and genitourinary rhabdomyosarcoma, the most common soft tissue sarcoma of childhood, represent two of the most commonly diagnosed pediatric urologic malignancies. The introduction and use of multimodal therapy (surgery, radiation, and chemotherapy) by the National Wilms Tumor Study (NWTS) and the Intergroup Rhabdomyosarcoma Study (IRS) groups have greatly improved the survival among children with these malignancies. Present survival rates for Wilms tumor exceed 85% and for rhabdomyosarcoma survival rates are approaching 80% as well. For Wilms tumor, current treatment trends suggest less intense therapy for those children with favorable histology tumors who are considered at relatively low risk for tumor recurrence. Likewise, the significant morbidity associated with the present therapy regimens for rhabdomyosarcomas has prompted investigators to search for individualized management schemes for children with a high probability of responding. The need for accurate criteria to separate these high and low risk groups becomes imperative. In this review we present our work using nuclear morphometry, as a prognostic indicator, to retrospectively predict response to therapy for children with Wilms tumors and genitourinary rhabdomyosarcomas.

Adolescent↗

Morphometry of dermal collagen orientation by Fourier analysis is superior to multi-observer assessment.

In human dermis, collagen bundle architecture appears randomly organized, whereas in pathological conditions, such as scar tissue and connective tissue disorders, collagen bundle architecture is arranged in a more parallel fashion. Histological examination by one or two observers using polarized light is the most common method to determine collagen orientation. The hypothesis on which this study is based is that an objective image analysis technique, Fourier analysis, would improve the reliability (are the measurements reproducible?) and the accuracy (does the method measure what it is supposed to measure?) of collagen orientation assessment, compared with observer ratings. Fourier analysis was applied to 271 images of scar tissue and normal skin that were acquired by confocal laser-scanning microscopy. Observers rated the same areas using polarized light as well as the confocal microscopy images. Computer images consisting of different types of ellipses were generated with a fixed orientation. Observers and Fourier analysis evaluated the images to evaluate accuracy. The inter-observer reliability was acceptable when at least three observers rated polarized light images (r > 0.69), whereas two observers were sufficient for rating confocal microscopy images (r > 0.71). Fourier analysis correlated better with observer ratings of confocal microscopy images (r = 0.69) than with polarized light microscopy images (r = 0.42). Fourier analysis was more accurate than four observers for the evaluation of the 'true' orientation for almost all types of computer-generated images. For the first time it is shown that Fourier image analysis is suitable for the morphometry of dermal collagen orientation and leads to a superior measurement of collagen orientation compared with subjective histological evaluation by several experts. If an evaluation is performed by conventional light microscopy, at least three observers are required to attain an acceptable inter-observer reliability.

Adult↗

Morphometry of bladder carcinoma: I. The automatic delineation of urothelial nuclei in tissue sections using an IBAS II image array processor.

Semi-automatic methods of morphometry require the boundaries of the objects under study to be drawn by hand. This is slow, tedious and does not guarantee accuracy. Complete automation, with recognition, detection and verification by computer is not yet feasible. Automatic detection of nuclear boundaries with observer verification provides a means of obtaining large amounts of data for analysis, quickly and with similar accuracy to manual tracing.

Cell Nucleus↗

Morphometry of gastric carcinoma: its association with patient survival, tumour stage, and DNA ploidy.

Morphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow-up data were available for these patients, which were drawn from a larger, previously reported series. The morphometric data were compared with patient survival, clinico-pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico-pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P < 0.01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico-pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P < 0.01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferative index.

Aged↗

Prenatal diagnosis of primary microcephaly in two consanguineous families by confrontation of morphometry with DNA data.

BACKGROUND: Prenatal diagnosis of autosomal recessive primary microcephaly (MCPH) is hampered by the fact that fetal head size is normal until late in the pregnancy, and by the vast genetic heterogeneity and impractically large size of the currently known genes for the disorder. OBJECTIVE: Combine DNA and morphometric approaches into earlier prenatal diagnosis of MCPH. METHODS: We evaluated two consanguineous families affected with MCPH with an ongoing, second-trimester pregnancy. Fetal heads were evaluated by serial ultrasound scannings, and DNA was sampled from parents, probands, and fetal cells, for a focused mutation search and linkage analysis. RESULTS: DNA linkage analysis and fetal head morphometry were concordant in one family and probably concordant in the second, showing a healthy fetus and an affected fetus, respectively. CONCLUSIONS: Cautious confrontation of linkage and morphometric data in selected cases of MCPH from consanguineous families may decrease false-positive and false-negative errors of second-trimester prenatal diagnosis.

Adult↗

Energy balance alters dunning R3327-H prostate tumor architecture, androgen receptor expression, and nuclear morphometry in rats.

BACKGROUND: We hypothesize that diet or energy restriction may alter prostate tumor architecture and nuclear morphometry in a manner predictive of indolent biology. METHODS: Adult male rats bearing the Dunning R3327-H tumor were provided free-access to the AIN76 diet or 30% diet/energy restriction for 16 weeks. Tumor tissue was harvested and stained for biomarker evaluation by quantitative digital image analysis. RESULTS: Compared to controls, tumors from restricted rats showed a contracted stromal compartment with an increased epithelial/glandular area, and a greater number of smaller and more homogeneous glands. In parallel, the nuclei in tumors harvested from diet-restricted rats were smaller in size, showed a lower proportion with androgen receptor (AR) staining, and reduced intensity of AR staining. CONCLUSIONS: Our observations support the hypothesis that diet/energy restriction alters prostate tumor architecture, AR expression, and nuclear morphology consistent with a more differentiated and less aggressive phenotype.

Animals↗

Effect of melatonin on the anuran thyroid gland: follicle cell proliferation, morphometry, and subsequent thyroid hormone secretion in vitro after melatonin treatment in vivo.

The thyroid gland controls the progress of metamorphosis, although other hormones influence metamorphic rate, including melatonin, which may coordinate metamorphosis with seasonal and light conditions. Melatonin directly antagonized the action of thyroxine (T4) in promoting regression of tadpole tail tips in vitro, and this study sought to determine if it affects the thyroid axis of tadpoles as well. In an experiment sampling at 8-hr intervals for 24 hr, after melatonin treatment (15 micrograms/day for 12 days) of premetamorphic Rana pipiens tadpoles at approximately 1100 hr on 18L:6D, thyroid follicle cell height and lumen diameter were lowered by melatonin, but follicle cell proliferation was not significantly depressed. In a second experiment conducted under the same conditions, but sampling at 3-hr intervals for 24 hr, melatonin significantly lowered follicle cell labeling index and suppressed its ultradian (7.6 hr) rhythm, while shifting the peak of follicle lumen diameter to the dark instead of the light. Thus, melatonin tended to depress the thyroid of young tadpoles and suppress or shift its rhythms. Melatonin (10 micrograms/day for 5 days) injected into prometamorphic Rana catesbeiana tadpoles at 1930 hr on 18L:6D significantly altered subsequent in vitro thyroid function as determined by radioimmunoassay of media collected at intervals for 54 hr from cultured thyroids of injected control and melatonin groups, and a noninjected control group. Melatonin decreased T4 secretion during the first 30 hr, but not during the last 24 hr of culture, suppressed 3,5,3'-triidothyronine (T3) secretion for 12 hr, and then raised T3 output into the media above the control for the remainder of the culture period, increasing the T3:T4 ratio. Injection alone increased both T3 and T4 secretion for the first 30 hr, but did not change the T3:T4 ratio. The findings show that exogenous melatonin administered in vivo significantly modulated thyroid activity and morphometry directly and/or indirectly and comprise the first demonstration of an effect of melatonin on the amphibian thyroid gland.

Animals↗

The significance of histology and morphometry in predicting lymph node metastases in patients with squamous cell carcinoma of the vulva.

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the kappa coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter--mean nuclear volume--determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.

Adult↗