Biomedical subjects

M Scarpelli

Publications and source records attributed to M Scarpelli.

At least 19 recordsLinked to original sources

PubMed2003

Mucinous adenocarcinoma with superficial stromal invasion and villous adenoma of urachal remnants: a case report.

This report describes a case of mucinous adenocarcinoma with superficial stromal invasion and villous adenoma originating in the dome of the urinary bladder. Although no urachal remnants were identified, the location suggested urachal derivation. Only two previous cases of urachal adenocarcinoma with features of early stromal invasion associated with a villous tumour have been described.

Adenocarcinoma, Mucinous↗

PubMed2002

Predictive factors in prostate needle biopsy.

Prostate cancer (PCa) is a leading cause of morbidity and mortality in men, accounting for approximately 30% of all new cases of cancer and approximately 14% of cancer deaths. Despite considerable advances achieved in the ability to detect and treat PCa, there have not been significant corresponding decreases in PCa-related morbidity and mortality. Proper examination of prostate biopsy specimens by pathologists is critical in determining the type of treatment and predicting patient outcome. The goal is to tailor the therapeutic approach to the clinical, morphological and molecular features of each patient.

Adenocarcinoma↗

PubMed2002

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.

OBJECTIVE: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. MATERIALS: Experiences derived from medium power (sampling density 2.4 pixels/microm) and high power (6 pixels/microm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. RESULTS: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. CONCLUSIONS: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.

Computers↗

PubMed2002

Changes produced in the urothelium by traditional and newer therapeutic procedures for bladder cancer.

A handful of traditional and newer therapeutic procedures, such as chemotherapy, immunotherapy, radiotherapy, photodynamic and laser treatment, and gene therapy, are used to treat epithelial malignancies of bladder origin. These treatment modalities, used either intravesically or systemically, produce morphological changes in the urothelial mucosa that can be mistaken for carcinoma. The pathologist must be able to separate toxic and drug related alterations from tumour related changes. The clinical history is usually invaluable in this assessment.

Antineoplastic Agents↗

PubMed2001

Assessment of radical prostatectomy specimens and diagnostic reporting of pathological findings.

Proper examination of radical prostatectomy (RP) specimens from patients with prostate cancer (PCa) is critical for determining the need for adjuvant treatment and for predicting the outcome. The first step in the examination is represented by the assessment of the specimens. This includes proper fixation in formalin and whole-mount sectioning. The second step is related to the diagnostic reporting of pathological findings. This includes the evaluation of tissue features such as Gleason grade, stage and margin status. These three parameters, together with serum prostate-specific antigen (PSA) determination, are predictive factors whose prognostic role has been demonstrated in several studies.

Adenocarcinoma↗

PubMed2001

Multimegapixel images in histopathology.

OBJECTIVE: To describe methods and procedures for the assembly of very large scale microscopic image arrays. STUDY DESIGN: Microscopic imagery was recorded on different video microphotometers, equipped either with a three-chip CCD Sony MD 760 (Park-ridge, New Jersey, U.S.A.), a COHU vidicon (San Diego, California, U.S.A.) or a PROGRES camera (JenOptik, Jena, Germany), yielding image tiles of 512 x 470, 512 x 470 or 1,496 x 1,120 pixels, respectively. The slide was moved while mounted on a Maerzheuser scanning stage with 0.1-micron precision, under computer control. The MERGE software. (Optical Sciences Center, University of Arizona, Tucson, Arizona, U.S.A.) was written in C and currently implemented on a Sun. Ultra Sparc 2 computer (Sun Microsystems, Palo Alto, California, U.S.A.). RESULTS: The MERGE program allows the assembly of very large scale digitized image arrays preserving exact tile alignment such that even within a single nucleus, highly precise registration is maintained. Images up to 150 megapixels have been assembled, although most practical applications required assembly of only 60-300 tiles. CONCLUSION: The single limiting effect of assembling very large image arrays is the problem of angular misalignment between CCD scan line orientation and scanning stage travel direction. For misalignment of even less than 1 degree, very large arrays need substantial tile overlap. For object areas extending over only 5-10 mm, the effects can be controlled.

Computers↗

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↗

PubMed2000

Chromatin texture analysis of cortical adrenal gland adenomas, including incidentalomas, and adjacent normal-appearing cortical tissue.

OBJECTIVE: To describe, by morphometric and chromatin texture analysis, a series of adrenal gland lesions, including Cushing's and Conn's adenomas and incidentalomas. STUDY DESIGN: The material for the study consisted of five consecutive cases of incidentaloma, three cases of Conn's adenoma and three cases of Cushing's adenoma. Also included were five cases of adrenal carcinoma. Sections were stained according to the Feulgen procedure. Measurements were taken from the nodules and from two different zones, identified as outer and inner parts, of the normal-appearing adrenal cortex adjacent to the tumor. Data on approximately 50 nuclei were recorded for each of these three sites (tumor and outer and inner normal-appearing adrenal cortex). The nuclei were subjected to feature extraction and were analyzed by identification procedures--i.e., establishing nuclear and lesion signatures. RESULTS: The total optical density (OD) distributions of the nuclei from the normal-appearing adrenal cortex pointed to their diploid or near-diploid nature. In incidentalomas there was a very small increase in the number of nuclei, with increased total OD. In Conn's adenoma there was a noticeable but modest extension of the total OD distribution into the higher OD range. This trend continued for Cushing's adenoma. The pixel OD histograms for nuclei from normal-appearing tissue and from incidentalomas were hardly distinguishable. Starting with nuclei from Conn's adenoma, a shift toward lower pixel OD values began. The trend continued for nuclei from Cushing's adenoma and was very pronounced for nuclei from carcinoma. The nuclear signatures showed no appreciable difference between nuclei from normal-appearing cortex and from incidentaloma. Nuclei from Conn's adenoma were more similar to those from normal tissue in their signatures than nuclei from Cushing's adenoma. In fact, the nuclear signatures from Cushing's adenoma were almost identical to those of carcinoma. The lesion signatures for normal tissue, incidentaloma and Conn's adenoma confirmed the results seen in the nuclear signatures. There was a very modest increase in the number of nuclei with greater deviation from normal in incidentalomas, and the trend was more obvious in Conn's adenoma. However, in Cushing's adenoma there was a very substantial increase in the number of nuclei, with large deviations of their nuclear chromatin texture from normal. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex and highlighted the similarity between incidentalomas and adjacent normal-appearing cortex and between Cushing's adenoma and adrenal carcinoma.

Adenoma↗

PubMed1999

Subtle morphological and molecular changes in normal-looking epithelium in prostates with prostatic intraepithelial neoplasia or cancer.

BACKGROUND: Prostate cancer develops over an extended period of time. Until recently, the events initiating the process and the developments concomitant with the evolution towards invasive disease were largely unknown. METHODS: Analytical and quantitative methods are applied to provide insights into certain individual molecular events and their effects on the complex multiple feedback system of cellular metabolism and regulation in prostate neoplasia. RESULTS: Prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa) are associated with or possibly preceded by changes in the chromatin of secretory cell nuclei. The changes are detectable with a Bayesian belief network and quantifiable by computer image analysis in prostatic tissue that still appears histologically normal. In addition, normal-looking prostate epithelium shows some molecular changes similar to those present in the associated preneoplastic and neoplastic lesions. Such changes are also occasionally present in normal prostate glands without PIN and cancer. CONCLUSIONS: The subtle morphological and molecular changes of normal-looking epithelium might be seen as the onset of the development of prostatic neoplasia.

Adenocarcinoma↗

PubMed1999

Distinguishing cortical adrenal gland adenomas from carcinomas by their quantitative nuclear features.

OBJECTIVE: To explore data from a set of cases of adrenal cortical adenomas with different endocrine syndromes and carcinomas to determine whether quantitative image analysis of nuclear features might be used to separate the groups. STUDY DESIGN: Fifteen adrenal cortical tumors in which clinical information and optimally preserved, paraffin-embedded tissue were available were used. There were 10 adenomas and 5 carcinomas. Among the adenomas, five were associated with primary hyperaldosteronism (Conn's syndrome) and five with Cushing's syndrome. Five-micrometer-thick sections were stained with hematoxylin and eosin. In each case 50 nuclei were measured, and a number of morphometric and densitometric features were extracted. The data were subjected to multivariate analysis. RESULTS: Quantitative analysis showed that nuclei from adrenal carcinomas are larger than those from adenomas. Total optical density (OD) had a near-diploid distribution in the adenomas, while it was clearly aneuploid in the carcinomas. The pixel OD histograms were almost identical for all groups. Differences in nuclear chromatin texture were found between adenomas and carcinomas and also between the two adenoma categories. Multivariate analysis showed good discrimination between carcinomas and adenomas (Wilks lambda = .628, P < .0001) and between adenomas. However, based on Bayesian decision boundaries, 20-25% of carcinoma nuclei could be expected to be in the range of adenoma, and about 12% of Cushing's adenoma nuclei and 15% of Conn's adenoma nuclei would be classified as carcinoma. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex.

Adenoma↗

PubMed1999

Quantitative analysis of changes occurring in muscle vastus lateralis in patients with heart failure after low-intensity training.

OBJECTIVE: To quantitate the changes occurring in muscle vastus lateralis after exercise training of low intensity adopted for the rehabilitation of patients with chronic heart failure. STUDY DESIGN: Nine consecutive males with a clinical diagnosis of idiopathic dilated and ischemic cardiomyopathy underwent an eight-week period of training. The intensity of the work was calculated as 40% of peak VO2. The program consisted of 30 minutes of cycling three times per week. A cardiopulmonary exercise test, hemodynamic measurements and echocardiographic studies were carried out. Needle biopsies were taken from muscle vastus lateralis before starting and after completing training. Quantitative analysis was carried out on sections stained with ATPase at pH 9.5 for measurement of the lesser diameter of type 1 and 2 fibers (by using an image analyzer) and on UEA 1-stained sections for capillary density and capillary/fiber ratio (by using a frame in the eyepiece of the microscope). The Wilcoxon test was applied to identify significant differences before and after training. Spearman's rank correlation coefficient was also calculated to highlight any correlation between the morphologic data and results of clinical tests. RESULTS: After completing the training program, all the patients experienced an improvement in exercise tolerance and a significant increase (P < .004) in the VO2 and VCO2 peak. Skeletal muscle showed a significant (P < .02) increase in the capillary/fiber ratio. The changes were not significantly correlated with any of the clinical findings. CONCLUSION: Low-intensity training can improve the functional capacity of patients with heart failure while producing only mild morphologic changes in their muscles.

Adult↗

PubMed1997

Meningioma: the impact of new techniques for the diagnosis and prognosis.

Our knowledge of meningioma has expanded considerably in the last few years. Immunohistochemistry, cytogenetics and molecular biology have given an important contribution to this improvement. Meningiomas can have almost endless variations in cellular morphology, architectural patterns and metaplastic changes. The majority of them have no prognostic implications. But a few variants should be recognised because of peculiar clinico-pathologic correlations or biological behavior. Histological features useful in distinguishing benign from potentially aggressive meningiomas have been identified. According to the WHO classification meningiomas are classified as benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3). Since histological appearance fails to predict accurately the clinical behaviour in a significant percentage of meningiomas, the attention has turned from tumor histology to tumor biology. Proliferative indices can be used, together with other histologic features, in assessing the prognosis as well as the postoperative management of the patients. Karyotyping may be of use to identify a subgroup of patients at higher risk for recurrence who may need special follow-up and treatment. The most consistent chromosome aberration in meningiomas seems to be a monosomy 22. As the karyotype becomes progressively abnormal, the tumor becomes more aggressive. Molecular genetic analysis has shown that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. P53 immunoreactivity is not always associated with the gene mutation but is not detectable in benign meningiomas.

Journal Article↗

PubMed1997

Computer-assisted discrimination of glioblastomas.

OBJECTIVE: To measure a number of nuclear features in a series of glioblastomas and compare the data with those from a set of anaplastic and low grade astrocytomas. STUDY DESIGN: The material consisted of toluidine blue-stained smears from 13 consecutive cases of glioblastoma. Smears from 12 high grade astrocytomas and 13 low grade fibrillary astrocytomas were used for comparison. Fifty nuclei were measured in each case. Cell images were segmented by an interactive procedure. A set of features representing both morphometric and nuclear texture characteristics was computed. RESULTS: The use of a discriminant function based on two features related to the gray value distribution resulted in the separation of all low grade astrocytomas from glioblastomas. When the corresponding discriminant function was computed for high grade astrocytomas and the values were plotted against optical density, the glioblastomas formed a group at a greater distance from the low grade astrocytomas than from the high grade astrocytomas. A second discriminant function based on two features allowed complete separation of the glioblastoma cases from the high grade astrocytomas. CONCLUSION: In our material, chromatin texture analysis allowed effective separation of astrocytic tumors with different histologic grades of malignancy.

Astrocytoma↗

PubMed1997

Computer-assisted analysis of medulloblastoma. A cytologic study.

OBJECTIVE: To explore data from a set of cases of medulloblastoma to see whether quantitative image analysis might suggest evidence for the existence of lower and higher grade lesions. STUDY DESIGN: Fourteen consecutive cases of medulloblastoma were obtained. Smears were stained with toluidine blue. For each case, 50 nuclei were measured and a number of densitometric features extracted. RESULTS: The existence of two subgroups of cases, identified as lower and higher grade groups, was suggested by a plot of the total optical density versus nuclear area. Two nuclear texture features--the number of pixels with the same optical density value occurring consecutively in the nucleus and the proportion of pixels in the high optical density range--divided the cases into the same subgroups. The use of a clustering algorithm established two clusters that corresponded to that subgrouping except for one case. Discriminant analysis gave an identical classification, with the misplaced case having a borderline discriminant function score. An unsupervised learning algorithm based on an adaptive distance metric formed two clusters and assigned the borderline case to the low grade subgroup. The grouping obtained by quantitative analysis was only partly related to the grade of nuclear atypia subjectively evaluated. CONCLUSION: In our series of medulloblastomas, quantitative analysis provided a means of detecting differences in the nuclear size and texture that allowed the classification of cases into two subgroups.

Adult↗

PubMed1996

Standardized mitotic counts in breast cancer. Evaluation of the method.

Twenty-one pathologists and technicians participated in a study evaluating the variation present in mitotic counts for prognostication of breast cancer. The participants counted the mitotic figures in 20 breast cancer samples from ten high power fields (mitotic activity index, MAI, giving the results in mitotic figures per 10 fields) and also made a correction for field size and area fraction of the neoplastic epithelium to get the standardized mitotic index (volume fraction corrected mitotic index, or M/VV index, giving the result in mitotic figures per square mm of neoplastic epithelium). The difference in variation between the two methods was not big, but the standardized mitotic index (SMI) showed consistently smaller variation among all participants and different subgroups. Experienced pathologists had the highest variation in mitotic counts, and specially trained technicians, the lowest. The efficiency of the mitotic counts in grading (the grading efficiency) was used to evaluate the mitotic counts. In groups without special training for mitotic counts the mean grading efficiency was lower (experienced and training pathologists both on average had the potential to grade 88% of the cases correctly) than in the group specially trained for the purpose (trained technicians had the potential to grade 95% of the cases correctly). Among the specially trained technicians, the grading efficiency was of the same magnitude as the grading efficiency achieved in determining the S-Phase fraction of cells from paraffin embedded breast cancers by flow cytometry in different laboratories. The results suggest that special training is helpful in making mitotic counts more reproducible, and that in trained hands, the mitotic counts give results comparable to more sophisticated methods of determining proliferative activity in breast cancer.

Breast Neoplasms↗

PubMed1996

TGF-beta 1 immunohistochemistry in goiter: comparison of patients with recurrence or no recurrence.

The aim of this work was to establish whether the immunohistochemical pattern for TGF-beta 1 in goiters that recur after thyroid surgery is different when compared with goiters that do not recur postoperatively. Twelve goiters, surgically removed by partial resection between 1977 and 1982, were studied. Ten years after surgery, 6 patients had recurrence of goiter or thyroid nodules (group 1); the others did not have any recurrence (group 2). The presence and location of TGF-beta 1 were evaluated a posteriori by immunohistochemistry in histological samples of the tissue that was removed. In each goiter specimen, 50 randomly selected subcapsular follicles were studied to evaluate the percentage of follicles negative or positive for TGF-beta 1 and the protein's intrathyrocyte location. In the slides of group 1, the percentage of TGF-beta 1-positive follicles was statistically (p < 0.01) greater (93.1%) than in group 2 (71.4%). No difference in the location of TGF-beta 1 was found. The authors found a greater percentage of positive follicles for the TGF-beta 1 protein in group 1 patients. In conclusion, TGF-beta 1 production in goiter is variable, time dependent, and may be a marker of active cellular proliferation due to chronic exposure to a goitrogen stimulus. Thus, the more TGF-beta 1 found, the more the cell is stimulated and, therefore, the greater the risk of relapse.

Adult↗

PubMed1996

Enhanced expression of transforming growth factor beta1 in rat thyroid hyperplasia is thyrotropin induced and time dependent.

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

Animals↗