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PubMed1995

Effect of chronic alcoholism on neuronal nuclear size and neuronal population in the mammillary body and the anterior thalamic complex of man.

The effect of chronic alcoholism on neuronal nuclear size and neuronal population of two memory-related diencephalic centres, the mammillary body and the anterior thalamic complex, has been examined in 24 chronic male alcoholics and 22 age-matched male controls. Cases were subdivided into three age groups (30-44 years, 45-59 years and 60-75 years). The results showed a significant reduction in both neuronal numbers and nuclear size in alcoholics compared to controls. Differences were especially high in the youngest alcoholics. The intensity of liver damage (steatosis vs. cirrhosis) did not have any significant effect. Moreover, an age-related decrease of neuronal number and karyometry was seen in controls but not in alcoholics. Our results suggest that chronic alcoholism accelerates the rate of neuronal loss in the mammillary body and anterior thalamic complex to a degree equivalent to aging. Likewise, chronic alcoholism impairs the compensatory increase in neuronal nuclei area seen in normal aging in these same structures. Our findings show that medial diencephalic memory centres are damaged in chronic alcoholism, which may contribute to the clinical symptomatology of these persons.

Adult↗
PubMed1976

CNS-endocrine pancreas system. I. The hypothalamus response to insulin deficiency.

The anterior, medial and posterior hypothalamic nuclei in alloxan-diabetic male rats were studied by karyometry. Selective responsiveness of separate nuclei of the medial basal hypothalamus (MBH) and the anterior hypothalamus was revealed. In the MBH cell nuclear-size changes were most prominent in the ventromedial nucleus and less pronounced, but significant, in the arcuate nucleus. In the anterior hypothalamus a significant response was produced by the supraoptic nucleus. The authors do not exclude the possibility that the reaction of the neurosecretory cells of the supraotic nucleus is indirect and reflects disturbed vasopressin balance in alloxan-diabetic rats in response to impairment of water-salt metabolism. The responsiveness of the MBH nuclei is considered as evidence for their involvement, the bentromedial nucleus in particular, in hypothalamic control of the endocrine pancreas. Various means by which insulin-sensitive hypothalamic areas may be implicated in this control are discussed.

Animals↗
PubMed1976

CNS-endocrine pancreas system. II. Response of dorsal nucleus of the vagus nerves to insulin deficiency.

Sensitivity of the vagal dorsal nucleus nerve cells to insulin deficiency was revealed in alloxan-diabetic rats by karyometry. Control measurements showed absence of similar changes in cell nuclear sizes of the adjoining area, the Nucltractus solitarii. The results provide evidence in favour of a selective response of the dorsal nucleus of the vagus nerves to insulin deficiency and allow assumption that not only the peripheral vagus but the central component of this cholinergic system contribute to endocrine pancreas control. It is suggested that the medial basal hypothalamus and the system of the vagus are links of a single control mechanism regulating endocrine pancreas and represented at different levels of the central and peripheral nervous system.

Animals↗
PubMed1993

[Vasopressin concentration in the cerebrospinal fluid and the structural indices of the function of the hypothalamo-neurohypophyseal system in aging and stress].

The radioimmunological analysis revealed an increase in the concentration of arginine vasopressin in the cerebrospinal fluid of rats during aging. This correlated with the results of karyometry of neurosecretory neurons of the supraoptic nucleus of the hypothalamus which showed an increase in the size of their nuclei. Under conditions of water deprivation of both adult and old rats, there was an increase in the above parameters being more marked in the adult than old rats. All this indicated pronounced changes of the vasopressin regulation in aging, limited reserves of the hypothalamic-neurohypophysial system, and age-related decrease of its response to stress. An enhanced role of the cerebrospinal fluid in accomplishment of vasopressin-induced regulation of brain functions in the old age was suggested.

Aging↗
PubMed1976

Karyometric studies of the nucleus preopticus in fish (Clarias batrachus) and toad (Bufo andersonii).

With the object of investigating the so called 'feedback' mechanism, whereby hormones from the various endocrine glands influence the hypothalamus in its regulation of the hypophysial tropic hormones, the activity of the nucleus preopticus (NPO) has been studied by means of karyometry under experimental conditions to understand the endocrine nature of the hypothalamic nuclei. (1) Oestrogen and testosterone propionate caused an increase in nuclear volume of the NPO cells, which is related to the synthesis of secretion. An increase of the nuclear volume is attributed to an increase of secretion. (2) Methylthiouracil (MTU) and thiourea bring about shrinkage in nuclear dimensions (p less than 0.001). Depletion of NSM is noticed in the hypothalamo-hypophysial neurosecretory system after MTU administration. (3) Two to five days' administration brings about depletion of NSM in the cells of the NPO. Eight to 15 days' metopiron treatment enhanced the activity of NPO cells. (4) Hypophysectomy caused shrinkage of the NPO cell nuclei, depletion of AF-stainable material in the cells of the NPO. ACTH treatment reversed these changes and brought about hypertrophy of the neurosecretory cells. (5) Neomercazole treatment and radiothyroidectomy bring about shrinkage in the NPO cell nuclei. Thyroidectomized toads when injected with thyroxine showed an enlargement of their nuclei.

Animals↗
PubMed1982

Estrogen-dependent changes in the functional interrelationships among neurons, ependymal cells and glial cells of the arcuate nucleus. Cytometric studies in the female albino mouse.

The synchronizing effect of ethinylestradiol (4 micrograms/g b.w.) on neurons of the arcuate nucleus 700-950 micrometers caudal to the posterior edge of the optic chiasma was studied by karyometry in 6-week-old albino mice during proestrus. The caudal portion of the arcuate nucleus was identified as the most estrogen-sensitive subdivision; all neurons showed an increase in their nuclear area (mean transect, profile area of the nucleus) 1 h following administration of ethinylestradiol. This hypothalamic region was selected for the subsequent electron-microscopic cytometric study to analyze functional interrelationships among neurons, ependymal cells and glial cells. Six and 12 days after ovariectomy no significant change in the nuclear area of neurons and ependymal cells was found 850-950 micrometers behind the posterior slope of the optic chiasma, but the neurons exhibited a decrease in the number of polyribosomes, the volume fraction (Vvmi) and the surface density of the inner membrane of mitochondria (Svmi). A similar decrease in Vvmi and Svmi was measured in the apical part of ependymal cells and in the pericapillary profiles of ependymal and glial cells, which was accompanied by a reduction in the surface density of ependymal processes extending into the ventricular lumen. In addition, no change of Vvmi and Svmi was seen in the basal subnuclear part of ependymal cells. This bipolar functional reaction of ependymal cells after ovariectomy is discussed as an indicator of ependymal control of neuronal activity by sequestering biologically active agents, e.g., transmitters of neurohormones, in their apical and basal extensions facing the ventricular surface or the pericapillary space.

Animals↗
PubMed1983

Testosterone-induced alterations in the reactivity pattern of the neurons in the arcuate nucleus of male mice. A karyometric study.

The effects of testosterone administration on the hypothalamic arcuate nucleus were studied in adult male mice by means of karyometry. Four animals per group were sacrificed 1, 2, and 3 h after intramuscular injection of 100 micrograms testosterone propionate/100 g body weight. The nuclear diameter of neurons was measured in serial coronal sections. Testosterone induced an increase in the nuclear diameter of neurons located in the dorsal and medial periventricular zones of the arcuate nucleus. The neurons exhibiting the greatest changes in nuclear diameter were situated in the rostral portion of the nuclear area examined. In the central portion of the arcuate nucleus no response to testosterone was found. The present data support previous observations showing mosaically arranged nerve-cell groups in this hypothalamic nucleus.

Animals↗
PubMed1983

24-hour-variation of pineal gland volume, pinealocyte nuclear volume and mitotic activity in male Sprague-Dawley rats.

In two experiments carried out on two alternate days, the 24-h-rhythmicity of pineal gland volume, pinealocyte nuclear size in cortex and medulla and mitotic activity were studied in male Sprague-Dawley rats, to assess to what extent morphological parameters reflect the pronounced day/night differences in pineal melatonin formation. Pineal volume exhibited statistically significant changes in the second experiment only, with a distinct trough at 6 p.m. Karyometry revealed highly variable patterns. In the first experiment, pinealocyte nuclear changes lacked parallelism in cortex and medulla. The cortex exhibited a bimodal curve with peaks at noon of the first day and at 6 a.m. of the second day, and two troughs at 6 a.m. and midnight respectively of the first day. The medulla showed no clear-cut rhythmicity. In the second experiment, cortex and medulla reacted similarly, nuclear size decreasing from 6 a.m. to 6 p.m., remaining low thereafter. Mitotic activity of pinealocytes is low (on average 23 mitotic figures/gland). In both experiments statistically significant differences existed between certain times, pointing in the direction of 24-h-rhythmicity, but whereas the curve exhibited a peak at midnight in the first experiment, mitotic activity in the second experiment showed a trough at midnight. It is concluded that for as yet unexplained reasons morphological parameters do not appear to accurately reflect circadian rhythmicity of pineal melatonin formation.

Animals↗
PubMed2000

Morphometric index of adult renal cell carcinoma. Comparison with the Fuhrman grading system.

Various grading systems have been proposed for renal cell carcinoma (RCC), using nuclear, cytoplasmic, and architectural features. The available evidence suggests that nuclear grading is a better prognostic indicator than other types of grading schemes. Nuclear morphometry may still improve the correlation of the nuclear grading with survival, however, because observer consistency is lacking in the subjective grading of RCC. The aim of this study was to investigate morphometrically whether RCC cases show a continuous spectrum of nuclear changes or whether there are discrete groups of cancer that correspond to the four Fuhrman grades. Karyometry was performed on 5- microm-thick, haematoxylin- and eosin-stained sections from 60 cases of conventional (clear cell) RCC. The analysis also included the evaluation of normal renal tissue (proximal tubules) adjacent to cancer. In each case the difference between the value of the cancer and the corresponding normal epithelium was calculated to represent, quantitatively, the degree of similarity between the tumour tissue and the internal normal control. When the differences were sorted into ascending order, a steady increase in values was observed for both the nuclear and the nucleolar features. A monotonic trend was evident for the differences in the mean maximum nuclear diameter and mean nucleolar area. When the differences between the values in the cancer and in the corresponding normal epithelium of these two features were summed up, the method resulted in a continuous variable, or nuclear morphometric index, related to the degree of deviation of each individual RCC from its internal normal control. The lowest index values were observed in of Fuhrman grade I cases, whereas values ranging from 2.679 to 5.422 were associated with cases graded II. Values equal to or higher than 5.951 were seen in the cases assigned to either grade III or grade IV. Partial overlap was present between the index values in grades III and IV. The RCC cases can be represented by a continuous index that corresponds to the morphological grading based on the Fuhrman scheme. This study shows that the index may be useful in supplementing the pathologist's grading. This issue can be further addressed with follow-up studies.

Adult↗
PubMed2000

Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections.

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high-grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 microm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 microm2 (SD 4.65) and 37.31 microm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 microm2 (SD 8.44), whereas it was 54.26 microm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 microm2 (SD 6.56) and 61.17 microm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 microm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy.

Aged↗
PubMed1992

Short-term ethanol intoxication in rat. Effect on the entorhinal cortex.

The effect of short-term ethanol intoxication in systems implicated in memory and other cognitive functions in rats has been assessed by studying the variation in the karyometry of the neurons in the different layers of the lateral entorhinal cortex. The analysis showed that short-term ethanol consumption produced a reduction in the nuclear area of neurons in layers V and VI, and to a lesser extent, in layers II and III. These results suggest that the deep layers of the entorhinal cortex are more sensitive to ethanol intoxication, thus more likely affecting cortical and subcortical projections than the hippocampal output.

Acute Disease↗
PubMed1995

Chronic alcoholism decreases neuronal nuclear size in the human entorhinal cortex.

The effect of chronic alcoholism in the neuronal nuclear area (karyometry) of the lateral entorhinal cortex at three rostro-caudal levels (rostral, intermediate and caudal) has been studied in 19 alcoholic subjects and in 15 aged-matched controls. Cases were distributed into three groups according to their age (29-44, 45-60 and 61-70 years of age). In the second group (45-60 years), the nuclear size in layers II and III of the caudal entorhinal cortex showed a very significant decrease compared to controls. The first group (29-44 years) also showed a significant reduction in size, while the third group presented the smallest differences. The presence of cirrhosis in the alcoholic group did not vary the observed results. Thus, chronic alcoholism significantly decreases the nuclear size in layers II and III of the lateral entorhinal cortex, and thus the entorhinal output to the hippocampus may be altered in alcoholism.

Adult↗
PubMed2005

Incidentally detected prostate cancer in cystoprostatectomies: pathological and morphometric comparison with clinically detected cancer in totally embedded specimens.

There are limited data regarding the pathological features of incidentally detected prostate cancer. Examination of cystoprostatectomy specimens obtained during bladder cancer treatment affords a unique opportunity to examine incidentally detected prostate cancer and determine its relationship with clinically detected prostate cancer obtained during radical prostatectomy. We compared the pathological findings of incidentally detected prostate cancer in 132 consecutive cystoprostatectomy specimens from patients treated for bladder cancer with a consecutive series of 228 radical prostatectomy specimens from patients treated for prostate cancer. All specimens were totally embedded and whole-mounted. Karyometry was evaluated in select subsets of patients from the study groups. Incidentally detected cancer was found in 42% of cystoprostatectomy specimens, and the cancers were of lower Gleason score and lower pathological stage with fewer positive surgical margins than in clinically detected cancers in age-matched radical prostatectomies. High-grade prostatic intraepithelial neoplasia (PIN) was present in 82% of radical prostatectomy specimens, in 70% of cystoprostatectomies with incidentally detected prostate cancer, and in 54% of cystoprostatectomies without prostate cancer. Mean nuclear and nucleolar area was lower in incidentally detected cancer and PIN when compared with clinically detected cancer and PIN, respectively, similar to the results with proliferative indices. We conclude that incidentally detected cancer is less aggressive than clinically detected cancer.

Humans↗
PubMed1998

Bladder wash cytology, quantitative cytology, and the qualitative BTA test in patients with superficial bladder cancer.

OBJECTIVES: Two new methods for the detection of transitional tumor cells in bladder wash (karyometry: QUANTICYT) and voided urine material (BARD BTA test) were compared with bladder wash cytology for the prediction of histology and tumor recurrence. METHODS: Bladder wash material and voided urine were sampled from 138 patients. Bladder wash karyometric (BWK) image analysis and the BTA test were applied. A subsequent urethrocystoscopy was performed and a bladder tumor, when present, was resected. Moreover, each patient was followed for tumor recurrence and progression. RESULTS: Sensitivities for the detection of tumors were 34.4%, 44.8%, and 69.0% for the BTA test, bladder wash cytology (BWC), and BWK, respectively (BTA versus BWC, P = 0.64; BTA versus BWK, P = 0.0002; BWC versus BWK, P = 0.0001, using the McNemar test). Specificities for the different tests were 81.3%, 92.5%, and 72.5%, respectively (BTA versus BWC, P = 0.096; BTA versus BWK, P = 0.031; BWC versus BWK, P = 0.001, using the McNemar test). Combinations of tests did not result in better prediction of the presence of tumor. Sensitivity of carcinoma in situ for the three tests was 0 of 3, 3 of 3, and 3 of 3, respectively. Follow-up analysis after a negative cystoscopy revealed comparable predictive values for BWC and BWK. CONCLUSIONS: The BTA test may be useful for patients with recurrent, low-grade papillary lesions. However, sensitivity for detection of these lesions, although higher than that for BWC, was only 42.9%. The highest specificity was found for BWC; however, this was accompanied by the lowest sensitivity of all three tests. The lower specificity of BWK was accompanied by a better prediction of tumor recurrence after a normal urethrocystoscopy. BWK is particularly sensitive for the recurrence of high-grade bladder lesions.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Vasopressin, hypothalamo-neurohypophyseal system and aging.

Based on the authors' own data and a review of current literature, the role of vasopressin (VP) in the mechanisms of age-related changes, development of stress-reactions and pathology onset is discussed. In aging, the VP concentration in blood and cerebrospinal fluid increased, its level in pituitary rose and that in hypothalamus fell. Under stress (emotional-painful stress, water deprivation) the potential capabilities of the VP-ergic system decreased with age. The role of weakening central monoaminergic influences with aging in changing the intensity of VP secretion is discussed. The results of an ultrastructural analysis and karyometry of the neurosecretory cells testify to an adequate preservation of their protein-synthesizing system and a high level of secretory activity in old age.

Journal Article↗
PubMed1992

Nuclear morphometry of primary B cell thyroid lymphoma.

Thyroid lymphoma is usually distinguished from anaplastic thyroid carcinoma and from Hashimoto's thyroiditis by morphological and immunohistochemical assessment of tissue sections. Our objective was to assess the value of nuclear morphometry in the differential diagnosis of these conditions. Nuclear area measurements were performed on 10 cases of thyroid lymphoma using an IBAS 2000 Image Analyser and compared with similar measurements performed on 10 cases of Hashimoto's thyroiditis and 2 of anaplastic thyroid carcinoma. It was found that karyometry demonstrated differences between all three conditions, the cases of thyroiditis being distinguishable from lymphoma on the basis of mean nuclear area alone. Mean nuclear area for lymphomas was greater than for Hashimoto's thyroiditis and lower than for anaplastic carcinomas. The mean nuclear area also reflected the grade of lymphoma, with the exception of one case which had a large reactive T cell population. It is concluded that nuclear morphometry provides valuable information in the diagnosis and assessment of thyroid lymphomas.

Adult↗
PubMed1997

Dynamic changes in quantitative features of human gastric lesions.

Quantitative DNA, morphometric cellular and nuclear variables were evaluated in surgical biopsies from patients with various gastric lesions: chronic gastritis, chronic ulcers, adenomatous polyps (gastric adenomas), primary carcinomas and their corresponding lymph-node metastases. Paraffin-embedded tissue sections were studied by static cytophotometry (plug method), karyometry (measurements with a graduated eyepiece micrometer of the major and minor axes of the elliptic nuclear profiles, and calculation of profile areas), and measurements of cellular profiles (largest and smallest caliper diameters). Tissue lymphocytes from the same slide were used as diploid controls for the DNA evaluations. An increase of both cellular and nuclear dimensions and DNA content was noted in all pathological tissues, as compared to normal mucosa; the highest values are found in primary gastric carcinomas. A progressive pattern increase of cellular and nuclear dimensions and of DNA content was observed through normal to cancerous tissues, chronic gastritis, chronic ulcers and adenomatous polyps (adenomas). Lymph-node metastases, in our study, had smaller nuclear (cellular) dimensions than primary cancers.

Adenocarcinoma↗
PubMed1999

Selective nuclear morphometry as a prognostic factor of survival in renal cell carcinoma.

In the present study, we sought to determine the predictive value of selective nuclear morphometry (SNM) for patient outcome in renal cell carcinoma (RCC). Tumor samples of 140 renal adenocarcinomas diagnosed and treated with radical nephrectomy and hilar lymphadenectomy between 1970 and 1988 with a minimum follow up of 5 years in all the cases were studied by SNM. The morphometric analysis was performed in the most malignant tumor selected zone. Selection was based on cytological criteria including nuclear grade. Nuclear morphometric features analyzed were: area, perimeter, major diameter, major and minor diameter of the equivalent ellipse, volume of the equivalent ellipse and sphere, circumference diameter, and shape factors. The results showed that in the selected zone tumor nuclei were larger than in the zones selected at random. There was an inverse correlation between morphometric parameters and survival and a direct one between tumoral grade and stage. Tumors of the long-term survival group of patients presented nuclei with smaller morphometric measurements than tumors of short term survival group, with significant differences between them (p < 0.05). In the survival analysis carried out by the Kaplan-Meier method significant differences existed between different groups formed from break point for: area, perimeter, major diameter, major and minor diameter of the ellipse, volume of the ellipse and sphere, circumference diameter and perimeter shape factor. In the multivariate analysis carried out by the Cox method, the feature with the most predictable value related to survival, was the tumor stage. Morphometric value with the highest punctuation in the test was major nuclear diameter. The rest of the morphometric values (except elliptic shape factor and elongation factor) were also significant but they did not improve prognostic information of the major nuclear diameter. SNM offers a useful aid in a more objective grading of RCC. Multivariate Cox analysis revealed additional value of karyometry to tumor stage. SNM can be a useful tool for stratification of patients with RCC.

Adolescent↗