Biomedical subjects

Javier Regadera

Publications and source records attributed to Javier Regadera.

15 recordsLinked to original sources

PubMed2006

Primary testicular lesions are associated with testicular germ cell tumors of adult men.

The present study aims to establish the nature and frequency of testicular lesions in the parenchyma adjacent to testicular germ cell tumors (TGCT) to improve understanding of the factors involved in the development of testicular cancer. Fifty-three cases of TGCT that were fixed in both neutral-buffered formalin and Bouin solution, allowing for the nuclear characterization of Sertoli cells (SCs), were included in this study. In each case, at least 3 sections of different areas of preserved parenchyma surrounding the TGCT were studied. We found Leydig cell hyperplasia, microlithiasis, angiopathy, adenomatous hyperplasia of the rete testis, SC nodules, SC dysgenesis and involution, SC-only tubules, tubular atrophy, adluminal compartment lesions, hypospermatogenesis associated with spermatocyte sloughing, spermatogonial maturation arrest, and hypertrophic and multinucleated spermatogonia. These lesions were found in regions both adjacent and far away from the tumoral mass, and abnormal seminiferous tubules were found intermingled with those showing complete spermatogenesis, suggesting that these lesions are primary and existed before the development of the tumor. Our study suggests that SCs might play a more important role in the development of testicular tumors than previously thought. Our data supports the hypothesis that there is an abnormal differentiation of SCs, caused either by genetic anomalies or by environmental agents during fetal life. This abnormal SC differentiation may cause not only primary spermatogenesis failure and spermatogenesis arrest at different levels, but may also contribute to the poor differentiation of gonocytes into spermatogonia. The abnormal gonocyte differentiation might favor the development of dysplastic germ cells that may later transform into intratubular germ cell neoplasia, unclassified type.

Adolescent↗

PubMed2006

PCPH expression is an early event in the development of testicular germ cell tumors.

Testicular germ cell tumors (TGCTs) include various malignancies with distinct pathologies that share a common precursor lesion (intratubular germ cell neoplasia, unclassified, ITGCNU, or carcinoma in situ, CIS). TGCTs, as a whole, represent a highly curable tumor paradigm, with high sensitivity to radiotherapy and, especially, to cisplatin-based chemotherapy. However, a percentage of cases display therapeutic resistance, and the molecular mechanisms underlying such resistant phenotype remain to be elucidated. We put forward the notion that expression of oncogenic forms of the PCPH gene, which are known to confer resistance to radiation and chemotherapeutic drugs, including cisplatin, may be expressed in TGCTs, and thus contribute to the development of therapeutic resistance. To begin testing this concept, we studied PCPH expression in human TGCT cell lines and in 54 solid tumors by RT-PCR, western immunoblot and immunohistochemistry. The results demonstrated that: i) PCPH is expressed in TGCT cell lines and tumors, including CIS; ii) its expression levels vary among different TGCT pathologies, being generally higher in well differentiated regions and lower in areas of predominant proliferation; iii) PCPH expression is substantially increased in tumors relative to matched normal testicular tissue; iv) tumor samples express PCPH polypeptides of low molecular mass, consistent with the known size of the PCPH oncoprotein, that are either absent from, or markedly reduced in, matched normal tissue. Collectively, these results positively identify PCPH as a good early molecular marker for testicular neoplasms, and strongly indicate that immunodetection of truncated PCPH polypeptides may be a useful diagnostic tool for TGCT.

Adolescent↗

PubMed2005

Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure.

OBJECTIVE: Liver growth factor (LGF), a mitogen for liver cells, reduces fibrosis in a rat model of cirrhosis. The present study assesses the possible vascular antifibrotic and antihypertensive effects of LGF treatment on spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR and normotensive Wistar Kyoto rats (WKY) were treated with LGF (4.5 microg LGF/rat i.p. twice a week for 2 weeks). Haemodynamic parameters were measured in anaesthetized rats. Vascular structure and function were studied in carotid arteries using optical and confocal microscopy, radioimmunoassay for desmosine, and isometric tension recording. RESULTS: LGF reduced systolic and diastolic blood pressure only in SHR. When compared to those of untreated SHR, carotid arteries from LGF-treated SHR showed: 1) a 50% reduction in collagen area and an increase in vascular smooth muscle cell number in the media, 2) no difference in total elastin content, but an increase in size of fenestrae in the internal elastic lamina, and 3) enhanced relaxation to acetylcholine, sodium nitroprusside, and forskolin. These effects were specific for SHR, since no changes were observed in LGF-treated WKY. CONCLUSION: Short-term treatment with a low dose of LGF induced a large improvement in vascular structure and function and significantly reduced blood pressure in a rat model of essential hypertension. The present results could open future research to explore the vascular effects of this endogenous factor in order to determine its potential as an antifibrotic and antihypertensive agent in humans.

Acetylcholine↗

PubMed2005

Malignant mixed tumor of the larynx.

BACKGROUND: Malignant mixed tumor of the larynx is a very rare neoplasm; only five cases have been reported, three in the English-language literature. METHODS: We report the case of a 69-year-old man with a 2-month history of hoarseness and a left laterocervical palpable mass. RESULTS: Total laryngectomy and bilateral radical neck dissection were performed. The tumor involved the glottic and subglottic regions and thyroid cartilage and extended to the anterior side of the larynx. Microscopically, the tumor was composed of three cellular types: epithelial cells, chondrocytes, and spindle cells. The epithelial cells resembled a moderately differentiated adenocarcinoma, the mesenchymal cells resembled a high-grade chondrosarcoma, and the spindle cells had immunohistochemical features of myoepithelial cells. The tumor metastasized to a cervical lymph node, with the three described components. The patient died 11 months after surgery. CONCLUSIONS: The lesion in this case was considered to be a malignant mixed tumor. Differences between this tumor and that of laryngeal chondrosarcoma are discussed.

Aged↗

PubMed2005

Granular changes in Sertoli cells in children and pubertal patients.

OBJECTIVE: To characterize lysosomes and histochemical function of granular Sertoli cells in developmental alterations. DESIGN: Prospective and retrospective study. SETTING: University hospital and research centers. PATIENT(S): Nineteen infantile and pubertal patients undergoing testicular biopsy; four rat testes for lysosomal study. INTERVENTION(S): CD-68, alpha-1-antitrypsin, vimentin, inhibin alpha subunit, and anti-mullerian hormone antibodies were evaluated. Morphometric measures in seminiferous tubules with and without granular Sertoli cells were obtained. Ultrastructural data of lysosomes in human and rat Sertoli cells were compared. MAIN OUTCOME MEASURE(S): Quantification of mean diameter of seminiferous tubules, tubular fertility index, and germ and Sertoli cell indexes were obtained in human testis. RESULT(S): Granular changes in Sertoli cells are due to the accumulation of large amounts of lysosomes. Vimentin immunoexpression in infantile and pubertal granular Sertoli cells was lower than in adjacent nongranular Sertoli cells. Inhibin was negative in granular cells. Anti-mullerian hormone-positive and -negative granular Sertoli cells were present within the same tubules. CONCLUSION(S): The presence of early granular changes in Sertoli cells in childhood and pubertal cryptorchidic patients, associated with other developmental alterations, suggests an intense and irreversible dysfunction of phagocytosis in the granular Sertoli cells. These alterations might be considered primary and irreversible anomalies of Sertoli cells, which might be contributing factors in the infertility seen in these patients.

Adolescent↗

PubMed2005

Paratesticular cysts with benign epithelial proliferations of wolffian origin.

Paratesticular cysts with benign epithelial proliferations (BEPs) are rare. Only 10 cases were found in a series of 431 paratesticular cysts and were classified as follows: cystadenoma, 5; papilloma, 2; and hamartoma, 3. Four cystadenomas showed multiple papillae lined by CD10+ epithelial cells with hyperchromatic nuclei. The remaining lesion showed areas with a microcystic, glandular, cribriform pattern, with small, benign glands without atypia. Urothelial papilloma presented BEPs with cytokeratin (CK) 7+ and CD10+ and CK20- umbrella-like cells. The mural papilloma was lined by proliferative cylindrical cells exhibiting strong CK7 and CD10 expression. The 3 Wolffian hamartomas were characterized by strongly CD10+ epithelium surrounded by smooth muscle cells. The consistent CD10 expression in BEPs of paratesticular cysts suggests a Wolffian origin. The differential diagnosis of paratesticular cysts with BEP vs metastatic prostatic and primary borderline or malignant tumors is discussed.

Adolescent↗

PubMed2004

Microlithiasis of the epididymis and the rete testis.

Testicular microlithiasis is a well-defined clinical and pathologic entity easily diagnosed through testicular echography; however, its association with cancer and infertility is now under debate. Many efforts have been done in recent years to clarify the spectrum of lesions observed in testicular microlithiasis, but no published data as to the existence of a possible microlithiasis of the epididymis and the rete testis have been found. We have observed microlithiasis of the epididymis and the rete testis in surgical (8 epididymis and 6 testis) and autopsy specimens (12 cases). In decreased order of frequency, microliths of the proximal spermatic way were seen in rete testis, epididymal duct, and efferent ducts. Intraluminal, subepithelial, and interstitial microliths were localized along these segments of the spermatic way. Subepithelial microliths were the most frequently found. A granulomatous reaction around the interstitial epididymal microliths, mimicking malacoplakia, was observed in 1 case. The differential diagnosis of microliths includes corpora amilacea, Michaelis-Gutmann bodies, calcium deposits, hyaline globules, and parasites, like the giant kidney worm Dioctophyme renale. In infants and young adults, microlithiasis of the epididymis and the rete testis is frequently associated with alterations in the development of the proximal spermatic way. In elderly adults, it is related to ischemia and obstruction of the spermatic way.

Adolescent↗

PubMed2004

Xanthogranulomatous funiculitis and orchiepididymitis: report of 2 cases with immunohistochemical study and literature review.

Two patients with xanthogranulomatous inflammation are described, one with involvement of the spermatic cord and the other with 1 testicle and epididymis affected. To our knowledge, only 12 cases of xanthogranulomatous orchiepididymitis have been reported previously, one of which also presented a xanthogranulomatous funiculitis. Clinically, our patients presented with spermatic cord enlargement (case 1) and chronic orchitis that did not respond to treatment with antibiotics (case 2). Histopathologically, both cases showed extensive xanthogranulomatous inflammation with numerous foamy macrophages that were associated with colonies of microorganisms suggestive of actinomyces in case 1. Additionally, Escherichia coli was cultured from the surgical specimen of case 2. The possible underlying pathology may be diabetes in case 1 and phlebitis associated with chronic orchitis in case 2. Differential diagnoses with other lesions that are rich in macrophages, such as malakoplakia, and those testicular neoplasms without serologic tumor markers are discussed.

Abscess↗

PubMed2004

[Physiopathology of the infertile testicle. Etiopathogenesis of varicocele].

OBJECTIVES: To review current theories about etiology of varicocele and pathogenic mechanisms leading to a progressive disorder of spermatogenesis in relation to the subfertility or infertility these patients may present with. To evaluate its current anatomical knowledge of the normal venous drain of the testicle and its variations that may condition relapse or failure of the treatment of varicocele. To systematically review pathologic testicular lesions in patients with varicocele. To establish factors that may have prognostic significance on post-treatment fertility. METHODS: We performed a systematic search in the Medline database for each of the proposed etiological and pathogenic theories on human varicocele. The evaluation of pathologic testicular lesions in patients with varicocele was obtained from the study of testicular biopsies performed at the Hospital La Paz in Madrid over the lost 30 years. RESULTS: Regarding the anatomical theories of varicocele, congenital absence or incompetence of the internal spermatic vein valves, difficult venous drain, augmented hydrostatic pressure of the internal spermatic vein, disorder of the fascial-muscular pump mechanism, and compression of the venous drainage system are considered, among others, potential etiological factors. Regarding possible pathogenic theories of varicocele, we evaluate disorders of testicular thermoregulation, hypoxia, toxic effect of renal and adrenal metabolites, certain endocrine disorders, obstruction of the spermatic tract, disorders of blood flow and epididymal vasculature, oxidative stress, gonadotoxins, apoptosis, and lastly the effect of varicocele on the contralateral testicle. CONCLUSIONS: Available data support the idea that etiopathogenesis of varicocele is multifactorial. Many classic etiopathogenic factors related to anatomy, embryology, obstruction, and hyperthermia still prevail in addition to new factors related to oxygen reactive species and apoptosis. However, many pathogenic and physiopathologic aspects of varicocele need to be elucidated yet. As a matter of fact, neither of these data alone may clearly explain the variable effect varicocele has on spermatogenesis and male fertility. So, it is necessary to establish histological criteria with proved prognostic significance that allow us to detect possible progression of testicular lesions after treatment.

Algorithms↗

PubMed2004

[The effect of seminal leukocytes on semen quality in subfertile males with and without varicocele].

OBJECTIVES: To compare the concentration of leukocytes and round cells in semen samples of subfertile males (SM), men with varicocele (VM), and fertile males (FM) to establish a possible relationship between leukocyte concentration, semen parameters (pH, concentration, mobility, spermatic morphology) and lipidic peroxidation of the spermatozoid. METHODS: We evaluated 298 semen samples from: 42 fertile males, 170 subfertile males, and 86 men with varicocele. Sperm tests were performed following WHO criteria. All samples with leukocyte counts higher than 1 million/ml were submitted for oxidative stress study (malonyldialdehyde in seminal plasma). RESULTS: Leukocyte concentration was higher in subfertile males and men with varicocele (2.5 +/- 2.1 x 10(6)/ml and 2.3 +/- 2.1 x 10(6)/ml) than in fertile males (1.1 +/- 0.1 x 10(6)/ml) (p 0.0001). In the same way concentration of round cells was higher in the SM group (6.5 +/- 0.3 x 10(6)/ml) and VM group (6.1 +/- 0.4 x 10(6)/ml) than in FM (4.5 +/- 0.4 x 10(6)/ml) (p 0.05). Spermatozoid concentration was lower in SM (42.1 +/- 2.4 x 10(6)/ml) and VM (9.9 +/- 3.5 x 10(6)/ml) than in FM (82.4 +/- 5.7 x 10(6)/ml) (p 0.0001). The percentage of spermatozoa with type "a" mobility was lower in the SM (14.1 +/- 0.9) and VM (19.9 +/- 1.4) groups than in the FM group (50.0 +/- 1.3) (p 0.0001). In the same way, "a + b" mobility was lower in the SF group (26.7 +/- 1.4) and VM group (34.1 +/- 1.9) than in the FM group (50.0 +/- 1.3) (p 0.0001). The SM group showed a lower percentage of normal forms (43.3 +/- 1.5) than the VM (50.0 +/- 1.6) and FM (60.6 +/- 1.3) groups (p 0.0001). When grouping by concentration of peroxidase positive cells, there were not statistical differences in the spermatic variables in SM, with the exception of progeny cells. Type "a" mobility in the VM group was lower in the peroxidase positive group than in the peroxidase negative group (p 0.005); "a + b" mobility was also lower in the peroxidase positive men than in peroxidase negative (p 0.01); in the progeny cells they were higher in the peroxidase positive males (4.2 +/- 0.4 x 10(6)/ml) than in peroxidase negative males (3.0 +/- 0.3 x 10(6)/ml). Malonyldialdehyde concentrations were significantly higher in seminal plasma of subfertile and varicocele males than in fertile males (p 0.006, and p 0.03). CONCLUSIONS: Increased number of semen lymphocytes is more frequent in subfertile and varicocele males than in fertile males. The increase of semen leukocytes is associated with deterioration of seminal parameters. Oxidative stress has a negative influence on seminal parameters in subfertile males of unknown etiology.

Adult↗

PubMed2003

Computer-assisted enhanced volumetric segmentation magnetic resonance imaging data using a mixture of artificial neural networks.

An accurate computer-assisted method able to perform regional segmentation on 3D single modality images and measure its volume is designed using a mixture of unsupervised and supervised artificial neural networks. Firstly, an unsupervised artificial neural network is used to estimate representative textures that appear in the images. The region of interest of the resultant images is selected by means of a multi-layer perceptron after a training using a single sample slice, which contains a central portion of the 3D region of interest. The method was applied to magnetic resonance imaging data collected from an experimental acute inflammatory model (T(2) weighted) and from a clinical study of human Alzheimer's disease (T(1) weighted) to evaluate the proposed method. In the first case, a high correlation and parallelism was registered between the volumetric measurements, of the injured and healthy tissue, by the proposed method with respect to the manual measurements (r = 0.82 and p < 0.05) and to the histopathological studies (r = 0.87 and p < 0.05). The method was also applied to the clinical studies, and similar results were derived of the manual and semi-automatic volumetric measurement of both hippocampus and the corpus callosum (0.95 and 0.88).

Abscess↗

PubMed2002

Gradual deregulation and loss of PCPH expression in the progression of human laryngeal neoplasia.

PCPH is a gene involved in the regulation of eukaryotic cell proliferation and stress response. Recently, analyses of human and animal solid tumors and cell lines suggested that PCPH protein deregulation may participate in neoplastic progression. To test this possibility, we first examined PCPH expression in several laryngeal carcinoma cell lines by Western analysis. The results showed the presence of altered PCPH polypeptides in these cells, accompanied by the loss of the PCPH form present in normal laryngeal epithelial cells, a deregulated expression pattern similar to that reported previously. We then analyzed PCPH expression in 59 dysplastic lesions of the human larynx, representative of the mild, moderate, and severe stages of the disease. Immunohistochemical data showed that, compared with normal laryngeal mucosa, PCPH expression in the dysplastic samples was associated with areas of epithelial cell maturation rather than with regions of increased proliferation. Furthermore, PCPH expression decreased parallel to the increase in cellular atypia of the dysplastic samples: PCPH either was expressed at very low levels or not expressed in cases of severe dysplasia/carcinoma in situ. This trend toward loss of PCPH expression along malignant progression of the larynx was confirmed by the low to null expression of PCPH in samples of invasive laryngeal carcinoma and by the complete absence of PCPH immunostaining in a laryngeal carcinoma-derived liver metastasis. These results indicated that PCPH protein analysis might allow for the distinction between grades of laryngeal dysplasia. In addition, detection of altered PCPH polypeptides by Western analysis potentially can be applied to the early identification of laryngeal squamous cell carcinoma.

Biomarkers, Tumor↗

PubMed2002

Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results.

We have studied an animal model of acute local inflammation in muscle induced by Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We have compared our data to those found using histopathology and segmentation maps obtained by the mathematical processing of three-dimensional T2-weighted MRI data via a neural network. The MRI patterns agreed satisfactorily with the clinical and biological evidence of the phases of acute local infection and its evolution towards chronicity. The MRS results show a statistically significant increase in inorganic phosphate and a significant decrease in phosphocreatine levels in the inflamed region. Image segmentation made with a self-organizing, neural-network map yielded a set of ordered representatives that remained constant for all animals during the inflammatory process, allowing a non-invasive, three-dimensional identification and quantification of the inflamed infected regions by MRI.

Acute Disease↗

PubMed2002

RhoA activation promotes transformation and loss of thyroid cell differentiation interfering with thyroid transcription factor-1 activity.

Highly specialized cells, the thyrocytes, express a thyroid-specific set of genes for thyroglobulin (Tg), thyroperoxidase, and the transcription factors TTF-1, TTF-2, and Pax-8. The implication of the small GTPase RhoA in TSH-mediated proliferation of FRTL-5 rat thyroid cells has been previously demonstrated. To further analyze RhoA function in thyroid cell proliferation and differentiation patterns, we combined transient and stable transfection assays to express different mutant RhoA forms in FRTL-5 cells. Constitutively active RhoA (FRTL-5-RhoA QL cells) exhibited a fibroblast-like phenotype with organized actin fibers, whereas cells expressing the RhoA negative dominant phenotype (FRTL-5-RhoA N19 cells) present a rounded morphology and lose normal cytoskeletal architecture. In addition, expression of the constitutively active form of RhoA results in TSH-independent proliferation and anchorage-independent growth and induces tumors when inoculated in nude mice. Interestingly, FRTL-5-RhoA QL cells express less Tg and TTF-1 than wild-type FRTL-5 (FRTL-5- vector) or FRTL-5-RhoA N19, suggesting a loss at the differentiation stage. This effect is mediated, at least in part, by a decrease in TTF-1 activity, since transient or stable expression of RhoA QL results in a reduction in the activity of the wild-type Tg promoter as well as an artificial promoter the activation of which depends exclusively on TTF-1. The similarity between RhoA effects and thyroid transformation by Ras suggests that RhoA may act as a downstream effector of Ras; in fact, the dominant negative RhoA N19 abolished the down- regulatory effect of Ras V12 over the Tg promoter. Taken together, these results show for the first time that active RhoA is able to transform FRTL-5 cells and that this effect is coupled to a loss of thyroid differentiation due to impaired TTF-1 activity.

Animals↗

PubMedDate not supplied

Age-related epididymis-like intratesticular structures: benign lesions of Wolffian origin that can be misdiagnosed as testicular tumors.

This study aims to characterize the epididymis-like intratesticular structures (ELITSs), a rare lesion found in elderly men. ELITSs were identified in 6 patients from a review of 1442 autopsies and 271 surgical specimens of adult men. Bilateral lesions were seen in 5 cases. The lesion was located in the proximity of the mediastinal rete testis (6 testes) and at the testicular periphery (4 testes), and at both central and peripheral locations in 1 case. The lesion is characterized by a pseudostratified cylindrical epithelium, with a robust pankeratin and 8, 18, and 19 keratin expression, focal vimentin expression, and apical CD 10 expression, similar to what is proper of the normal human epididymidis. The epithelial layer of ELITSs was surrounded by a thin layer of smooth-muscle cells. The adjacent testicular parenchyma was atrophied and the rete testis showed some associated degenerative lesions related to arteriosclerosis. The ELITSs are distinct from atrophic seminiferous tubules with a Sertoli cell-only pattern and from the benign glandular teratomatous component of an involution of a malignant testicular germ cell tumor, the so-called burn-out germ cell tumor. Clinical and histopathological data suggest that this lesion represents a late Wolffian differentiation similar to the initial segment of the epididymal duct, which represents an unusual manifestation of the aging process.

Aged↗