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Biomedical subjects

A Cardesa

Publications and source records attributed to A Cardesa.

At least 91 records · Page 5Linked to original sources

Experimental models of kidney tumors.

We here present in outline some outstanding results on the animal models of renal tumors submitted to the highest attention, which include two kinds of epithelial neoplasms: those developed from the epithelium lining each the renal tubules (renal cell tumors) and pelvis; the mesenchymal tumor of rat; and tumors with embryonal appearance: the nephroblastoma as well as the variant of it known as the estrogen-induced tumor in the hamster. The review deals with methods for tumor induction and the pathobiology of tumors, the latter mainly focused on the identification of the precise types of renal cells committed in tumor origin. The existence of closely related counterparts of these animal tumors in man is also emphasized, by representing a situation of great potentiality, already exploited, to improve understanding of both the nature and development of renal tumors in man.

Animals↗

Influence of pancreatic and biliary reflux on the development of esophageal carcinoma.

We previously presented an experimental model of Barrett's adenocarcinoma of the esophagus by demonstrating that esophagojejunostomy combined with subcutaneous injection of 2,6-dimethylnitrosomorpholine in Sprague-Dawley rats resulted in development of adenocarcinoma in the distal esophagus. The present study was devised to investigate the influence of pancreatic and biliary duodenal-content reflux on the induction of esophageal carcinoma. Three groups of 8-week-old Sprague-Dawley rats were controls: the first was exposed to pancreatic reflux, the second to biliary reflux, and the third to both. The other three experimental groups were similar except that a 1/100 LD50 dose of 2,6-dimethylnitrosomorpholine was injected subcutaneously weekly, starting on day 15. Carcinoma of the esophagus was induced only in animals receiving the carcinogen after exposure to either pancreatic reflux (3/22, 13%) or pancreatic and biliary reflux (9/27, 33%). Half of the carcinomas were adenocarcinoma and half were squamous cell carcinoma. These findings suggest that under these experimental conditions, in which the carcinogen is used in a low dose, esophageal carcinoma is induced only when pancreatic secretions are present in the duodenal-content reflux. Biliary reflux, however, appears to exert a cocarcinogenic effect when combined with pancreatic secretions. The clinical relevance of these findings needs further evaluation. Conceivably, the elimination of pancreatic and biliary duodenal-content reflux in patients with documented Barrett's mucosa may inhibit the progression from metaplasia to adenocarcinoma.

Adenocarcinoma↗

Barrett's disease: pathophysiology of metaplasia and adenocarcinoma.

Peptic ulceration arising in the lower esophagus lined by columnar epithelium was described in detail by Tileston in 1906. Although this concept was challenged in 1950 by Barrett, experimental and clinical evidence has now conclusively demonstrated that Barrett's metaplasia is an acquired condition and is a consequence of chronic reflux of gastric or duodenal contents or both. Current concepts suggest that unknown trophic factors present in these secretions stimulate proliferation of multipotential reserve cells located in the esophageal submucosal glands resulting in columnar metaplasia of the normal squamous epithelium with subsequent potential for malignant degeneration. Today, numerous patients are affected by reflux esophagitis, a lesser number by Barrett's metaplasia, and a smaller but ever-enlarging group by adenocarcinoma. Although high-grade dysplasia is considered a precursor to invasive adenocarcinoma, detection of this abnormal mucosa remains controversial and currently requires esophagoscopy with biopsy. Epithelial markers, such as increased activity of mucosal ornithine decarboxylase, sulfomucin production, nuclear DNA aneuploidy, and recently molecular analysis, have also been proposed to identify those paitents at increased risk for malignant degeneration. As more is learned about the pathogenesis of Barrett's disease, perhaps these cancers can ultimately be prevented.

Adenocarcinoma↗

Expression of cytokeratins in squamous cell carcinomas of the larynx: immunohistochemical analysis and correlation with prognostic factors.

The expression of distinct cytokeratin subtypes in squamous cell carcinomas (SQCC) of the larynx was examined by immunohistochemistry with a panel of monoclonal antibodies (MABs) and different immunophenotypes were correlated with known prognostic factors, such as tumor site, local extension, degree of morphologic differentiation and lymph node metastasis. Among 50 cases of laryngeal SQCC tested, all 22 low grade tumors (Broders I and II) reacted strongly with MABs AE1, AE3 and KB.12, which corresponds to the phenotype of non-neoplastic squamous epithelium of the larynx. MABs K8.13 and K8.60 were negative only in 1 and 4 cases respectively. In these tumors CAM5.2 was either negative (18 cases) or weakly positive (4 cases). In contrast, we found that of 28 high grade SQCC (Broders III and IV) tested, strong reactivity with MABs AE1, AE3, K8.12 and K8.13 was restricted to smaller subsets, whereas CAM5.2 immunoreactivity was seen in 16 cases (57%). By morphological criteria 31 out of 50 cases in our series of SQCC showed keratinization and 30 of these 31 showed coexpression of cytokeratins identified by MABs AE3, K8.12, K8.13 and K8.60 and 29 cases by MAB AE1. The remaining non-keratinizing SQCC showed heterogeneous immunoreactivity for AE1, AE3 and K8.12 in 13 cases, for K8.13 in 12 cases and for K8.60 in 5 cases. Thirty of the 50 SQCC tested had no known lymph node metastasis and of these, 29 reacted with MABs AE1, AE3, K8.12 and K8.13 respectively, the remaining cases being either unreactive or only weakly reactive. Statistical analysis showed no significant differences between cytokeratins expression in SQCC and either anatomical location or local extension (pT).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Morphological comparison between benign keratinizing cystic squamous cell tumours of the lung and squamous lesions of the skin in rats.

Approximately 700 cases of keratinizing cystic squamous lung lesions in rats were investigated by light microscopy in order to clarify the nomenclature and classification of these lesions. The structure of benign keratinizing cystic squamous cell tumours of the lung was compared to that of cystic squamous lesions in the skin of rats, with consideration of data from the literature. We conclude that the reviewed keratinizing cystic squamous cell lesions of the lung are true neoplasms and that the growth pattern of these cystic lesions is inconsistent with that of a simple cyst. In the development of squamous lung cancer, a continuum of proliferation from exaggerated metaplasia through benign cystic tumours to invasive squamous cell carcinomas can be observed.

Animals↗

Secondary (AA) amyloidosis associated with Castleman's disease. Report of two cases and review of the literature.

This article describes two patients with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic symptoms, anemia, an increased plasma level of acute phase reactants, and systemic amyloidosis. There were amyloid deposits on the vascular walls of the liver, spleen, and mesenteric lymphoid mass. On immunohistochemical studies, amyloid was shown to be of the AA type in both cases. After surgical resection of the mesenteric mass, clinical and laboratory manifestations improved, and the amyloidosis showed no progression in these patients 23 years and 1 year later. The authors' review of the literature shows a striking similarity of CD cases associated with amyloidosis in terms of the abdominal localization of the lymphoid mass, secondary pattern (AA type) of amyloidosis, and improvement of clinical manifestations after removal of the tumor, without progression of amyloid deposition.

Adult↗

Comparative study of spleen pathology in drug abusers with thrombocytopenia related to human immunodeficiency virus infection and in patients with idiopathic thrombocytopenic purpura. A morphometric, immunohistochemical, and ultrastructural study.

A morphometric and immunohistochemical study was performed to assess the spleen's alterations in patients with autoimmune thrombocytopenia and in drug abusers with thrombocytopenia (DAT) related to human immunodeficiency virus (HIV) infection. A total of 34 patients were included in the study: 20 DAT patients and 14 with idiopathic thrombocytopenic purpura (ITP). Twenty HIV-negative splenectomy patients without thrombocytopenia were included as controls. Spleen weight in DAT patients (323.25 +/- 149.96 g, mean + standard deviation) was significantly increased compared with the ITP (164.28 +/- 29.79 g, P < 0.0001) and control (175.50 +/- 49.14 g, P < 0.0001) groups. The mean diameter of lymphoid follicles in the spleens of DAT patients (446.83 +/- 99.16 microns, was significantly higher than in those of the control patients (370.87 +/- 55.30 microns, P = 0.019). In control patients' spleens, the number of platelets in Billroth's cords was significantly higher (59.54 +/- 32.72/10(4) microns 2) than in those of the DAT (2.13 +/- 1.42/10(4) microns 2, P < 0.0001) and ITP (P < 0.0001) patients. The number of macrophages and ceroid histiocytes per 10(4) microns 2 of red pulp was significantly increased in both DAT (5.14 +/- 1.90) and ITP (7.48 +/- 4.38) patients compared with the control patients (3.66 +/- 1.10, P < 0.0001) and P = 0.06, respectively), and in ITP patients compared with DAT patients (P = 0.0136). The number of granulopoietic precursors per 10(4) microns 2 of red pulp was higher in the spleens of DAT (1.41 +2- 1.46, P < 0.0001) and ITP (0.92 +/- 0.75, P < 0.0001) patients compared with those of the control group. Transmission electron microscopy studies demonstrated platelet phagocytosis by macrophages of Billroth's cords and presence of myeloid metaplasia in spleens of DAT and ITP patients. Immunohistochemical studies showed a depletion of CD4+ lymphocytes in the T zone of splenic white pulp and an increased number of CD8+ lymphocytes in red pulp of DAT patients' spleens compared with those of ITP and control patients. There were no significant alterations in dendritic reticular cell network in the DAT group compared with the ITP and control groups.

Adolescent↗

Brain banks and non nervous tissues.

Nervous system diseases may not be confined to neural tissue, but also affect other organs. These organs could be involved indirectly or could be simultaneously affected by the same pathological process. A brain bank (BB) should also guarantee the storage of specific organs primarily or secondary affected other than nervous system. Tissues from patients with primary nervous system diseases without or with unknown systemic involvement should also be stored. Samples stored will be identified and registered in a BB database for an accurate distribution and utilization of the material. To guarantee the best quality of the material stored, several techniques for the collection and preservation (cryopreservation, chemical fixation and microwave irradiation) and tissue management are described.

Brain↗

Clinico-pathological correlations in meningiomas: a DNA and immunohistochemical study.

We have studied 41 meningiomas classified histologically as benign, atypical or anaplastic. There were 26 females and 15 males and the mean age was 53 years. 36 tumours were supratentorial, 4 infratentorial and one spinal. Flow cytometry was performed on paraffin-embedded tissue using a selective staining technique for DNA. The ploidy index of DNA and percentage of cells in the S and G2/M phases were calculated. Results were correlated with clinical, histological and immunohistological data. 16/41 tumours were found to be diploid, 17/41 aneuploid and 8/41 could not be analysed. Significant correlations were found between aneuploid tumours and some qualitative features such as recurrence, pleomorphism, high cellular density, mitotic activity and brain and soft tissue infiltration. A high proliferative index appeared to be associated with clinical aggressiveness. No particular correlation between the expression of cytokeratin and epithelial membrane antigen markers and flow cytometry was found. Our results suggest that DNA flow cytometry in meningiomas may be of value in predicting the behaviour of these neoplasms and confirm that epithelial pattern in meningiomas is not linked to increased anaplasia or poor prognosis.

Adult↗

Pathological changes in organs of rats chronically exposed to hypoxia. Development of pulmonary lipidosis.

Rats were exposed to chronic normobaric hypoxia of progressively increasing severity; down to 8% or 7% oxygen concentrations. In addition to loss of weight, pathology revealed congestion, haemorrhages, hypertrophy of the heart involving mainly the right ventricle, thickening of arteries, ischaemic changes in the myocardium and extramedullary haematopoiesis in the spleen. Changes not described up until now were: 1) sheets of foam cells in the pulmonary alveoli; 2) foamy and solid storing cells in the spleen; 3) mucoid changes in the atrioventricular valve leaflets; 4) hyperplasia of the juxtaglomerular apparatus; 5) atrophy of the adrenal glomerulosa and hyperplasia of medulla; 6) atrophy of the perifollicular B-cell zone in the spleen; and 7) lipid pigment deposition in various organs. The findings indicate that severe chronic hypoxia induces a significant pulmonary lipidosis similar to that caused by amphiphilic cationic drugs, presumably by inhibiting hydrolytic enzyme activities. The observations are of importance in human hypoxic conditions and open the possibility of their rational treatment.

Adrenal Glands↗

The carcinogenic effect of 2,2-dioxopropylnitrosamine on the renal pelvic epithelium of Sprague-Dawley rats, after chronic subcutaneous injections.

The carcinogenicity of 2,2-dioxopropylnitrosamine on the urinary tract was investigated in three experimental groups of Sprague-Dawley rats (15 males, 15 females/group) by weekly subcutaneous administration for the life of the carcinogen at dose levels 1/5, 1/10 and 1/20 of the LD50, and compared with that in a similar group of untreated controls. It resulted in the induction of urinary tract tumours in 42 out of 79 effective animals (53%). Of these animals, 38 developed tumours within the renal pelvis. In the high-dose group, females had a 100% incidence of renal pelvic tumours, and males 73%. In all experimental groups, renal pelvic tumours were more frequent than ureteral and vesical ones. Histologically, the tumours were transitional cell papillomas and carcinomas, except for one squamous carcinoma. Out of 66 tumours, 42 (64%) were low-grade. High-grade tumours arose mainly in the renal pelvis of animals belonging to the highest-dose group. This experiment offers a useful model for the study of mechanisms involved in renal pelvic carcinogenesis.

Animals↗

Pathology of bone marrow transplantation.

For evaluating the therapeutic approaches in the follow-up and complications of patients treated with bone marrow transplantation (BMT), the histopathology is important on many occasions. The authors describe the different morphological changes that have an important role for treatment of these patients, classified according to their target organs of localization: skin, digestive tract, liver, and bone marrow. Graft-versus-host disease (GVHD) mainly affects the skin, gastrointestinal tract, and liver, and is sometimes difficult to differentiate from radiochemotherapy or infectious diseases. In the liver, the most frequent complications are GVHD, veno-occlusive disease, and infections. In the bone marrow, it is most important to evaluate the elimination of hemopathy and the reconstitution of normal hematopoiesis.

Bone Marrow Transplantation↗

Acquired renal cystic disease in HD: a study of 82 nephrectomies in young patients.

In order to study the development of acquired renal cystic disease (ARCD) and its potential complications, we studied, macro- and microscopically, 82 surgical specimens of nephrectomy carried out on young patients with chronic renal failure previous to renal transplantation. Statistical correlation of pathological findings with age, sex and time on hemodialysis (HD) have been done. There were 72 cases of ARCD (87.8%). It was statistically correlated with male sex (p less than 0.02) and prolonged time on HD (p less than 0.001) as has been previously reported. Hyperplasia of the cystic epithelium was found in 42 cases (52%), with 18 (22%) showing marked papillary proliferation. Also, there were 22 cases (27%) with renal adenomas. This incidence of hyperplastic and neoplastic proliferations, more than would be common in such a young population (males: 33.5 +/- 9.3 years; females: 35.4 +/- 11.7 years), suggests the potential of patients affected by ARCD to develop neoplasms. Thus, we consider that these patients must be checked periodically to detect possible malignant neoplasms.

Adenoma↗

Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas.

The p53 gene is a tumor suppressor gene located on chromosome 17p. Deletions of this chromosome and point mutations of p53 have been implicated in the development of colonic neoplasms. We have analyzed the loss of heterozygosity of the human p53 tumor suppressor gene in 40 cases of colorectal carcinoma using two restriction fragment length polymorphisms detected by BglII and AccII restriction enzymes. p53 gene product expression was studied immunohistochemically in 64 colorectal carcinomas, 18 adenomas, and 40 normal colonic mucosae using an anti-human p53 monoclonal antibody (Pab 1801) and the avidin-biotin-peroxidase complex technique. Twelve of the 40 patients (30%) were polymorphic for the p53 gene. In ten of these informative patients (83%), the tumor samples showed the loss of one allele when compared with normal colorectal samples of the same patient. One of the homozygous patients showed a loss of both p53 alleles. p53 immunostaining was observed in 43 of 64 carcinomas (67%) but only in two adenomas (11%). These two positive adenomas showed areas of carcinoma in situ. The normal mucosa was always negative. No relation could be found between p53 immunostaining and the degree of differentiation, the extension of the tumor, or the Ki-67 proliferative index. Mucinous carcinomas and right-side carcinomas were less p53 immunoreactive (25% and 52%, respectively) than the usual adenocarcinomas (73%) and distal tumors (72%). These findings suggest that p53 may be a target of chromosome 17 deletions and that this gene may play a role in the malignant transformation of adenomas. BglII and AccII restriction fragment length polymorphism analysis of the p53 gene may be a useful and direct technique to detect allelic loss of this gene in tumors.

Adenocarcinoma↗

Adult type of leukodystrophy. Krabbe's disease?

A 24-year-old man developed progressive dementia in seven years. The patient suffered a severe bronchopneumonia and eventually died few days later. Brain coronal sections showed a soft gray-brownish discoloration of white matter of centrum ovale but the subcortical arcuate fibers and the interne capsule were preserved. Microscopically, the white matter showed marked loss of myelin and oligodendrocytes, abundant hypertrophic astrocytes and numerous "globoid cells". The latter showed strong positivity in immunostains for a mouse monoclonal antigalactocerebroside antibody. The presence of these cells in the brain white matter might be the morphological basis to classify the present case as one of Krabbe's Leukodystrophy.

Adult↗

Human chorionic gonadotropin in esophageal carcinomas. An immunohistochemical study.

We have examined immunohistochemically the presence of human chorionic gonadotrophin (hCG) in 29 esophageal carcinomas: 24 squamous cell carcinomas, 2 adenocarcinomas, 2 adenoid cystic carcinomas and 1 adenosquamous carcinoma. In hCG-positive tumors, the presence of human placental lactogen (hPL) and pregnancy-specific beta-1 glycoprotein (SP-1) was also assessed. HCG immunoreactive cells were found in 5 squamous cell carcinomas (21%) and in none of 5 non-squamous cell tumors. The hCG positive cells were found in the most infiltrating areas of the tumors where poorly differentiated and pleomorphic cells predominated. The positive tumors were 4 poorly differentiated (31%) and one moderately differentiated carcinoma (12%). Four out of 10 cases (40%) with lymph node metastases had hCG in the primary tumor, whereas only one out of 11 cases (9%) without metastases was hCG positive. HPL and SP-1 were found in two cases. These placental proteins were detected in similar areas than hCG but the number of hPL and SP-1 immunoreactive cells was lower than hCG positive cells. SP-1 was also seen in areas of squamous cell differentiation negative for hCG. None of these two cases showed trophoblastic differentiation.

Adenocarcinoma↗