Tissue Dysplasia Research Articles

Epileptiform discharges in the human dysplastic neocortex: in vitro physiology and pharmacology.

Field potential and intracellular recordings were made in slices of human neocortical tissue obtained during surgery for the treatment of seizures associated with focal cortical dysplasia. Ictal-like epileptiform discharges, along with isolated field potentials, were induced by bath application of 4-aminopyridine (50-100 microM). Some of the isolated field potentials were associated with fast transients representing population spikes. Field potential profile analysis indicated that both types of synchronous activity had maximal negative values at 1,400 to 1,600 microm from the pia. The intracellular counterpart of the ictal-like discharge was a prolonged membrane depolarization capped by repetitive action potential burst firing. By contrast, the isolated field potentials were mirrored by long-lasting depolarizations with minimal action potential firing; only when population spikes occurred, the isolated field potentials were associated with epileptiform action potential bursting. Ictal-like discharges were abolished by either N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor antagonists. In contrast, the isolated field potentials continued to occur synchronously during excitatory transmission blockade (although they lacked fast transients) but were abolished by the gamma-aminobutyric acid(A) receptor antagonist bicuculline methiodide (n = 2 slices). Our study demonstrates that focal cortical dysplasia tissue maintained in vitro has an intrinsic ability to generate ictal-like epileptiform events when challenged with 4-aminopyridine. These discharges depend on excitatory amino acid receptor-mediated mechanisms. Our results also show the presence in focal cortical dysplasia tissue of glutamatergic-independent synchronous potentials that are mainly contributed by gamma-aminobutyric acid(A) receptor-mediated conductances.

Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization.

Retinoids exhibit multiple functions through interaction with nuclear retinoid receptors and have growth-suppressive activity on gastric cancer cells. To better understand the roles of nuclear retinoid receptors during gastric carcinogenesis, we have used in situ hybridization to investigate expression of retinoic acid receptors (RARs) and retinoid x receptors (RXRs) in premalignant and malignant formalin-fixed paraffin-embedded gastric tissues. Histological sections of eight normal, 17 distal normal and nine gastric cancer tissues were hybridized with non-radioactive RNA probes for subtypes of RAR and RXR. Expression of RARα, RARβ, RARγ, RXRα and RXRβ was found in most cell types in gastric mucosa tissues from normal individuals as well as in distal normal tissues from cancer patients. Expression of RARα and RARβ were found in three and seven cancer tissues, respectively, and levels of RXRα mRNA were significantly decreased in poorly differentiated cancer tissues. Among the five investigated nuclear retinoid receptors, only expression of RARα mRNA was significantly decreased in intestinal metaplasia, dysplasia and cancer tissues when compared to adjacent normal tissues. In conclusion, normal gastric mucosa expressed both RARs and RXRs, which supports the physiological role of retinoic acid on normal gastric mucosa. The decrease in RARα expression in premalignant and malignant gastric tissues suggests a significant role of RARα during gastric carcinogenesis. © 1999 Cancer Research Campaign

Comparison of Nuclear Matrix Protein Composition in Colon Cancer and Dysplasia

Background: Abnormal nuclear morphology associated with cancer may reflect changes in the proteins of the nuclear matrix. Methods: Nuclear matrix (NM) proteins were isolated from colonic tissue and analyzed by two-dimensional gel electrophoresis. Results: Several matrix proteins that were found in ulcerative colitis (UC) dysplasia (n = 5) and/or UC cancer (n = 4) were not identified in normal colonic tissue. UC dysplasia tissue showed three specific NM proteins with molecular masses of 49.2 kDa, 20.0 kDa, and 19.0 kDa, whereas 29.0-kDa and 32.0-kDa proteins were specific to UC cancer. Three proteins with 59.5-kDa (pI 6.3 and 6.6) and 33.75-kDa (pI 7.5) masses were common to both dysplasia and cancer tissue. Conclusions: These data suggest that NM proteins may have a role in the transition of tissue towards the malignant phenotype.

Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas.

Proteases are important for neoplastic invasion but a specific role for the plasminogen activator system in the progression of colorectal epithelial dysplasia to adenomatous lesions remains unclear. Consecutive tissue cryosections of 51 adenomas, 49 distant mucosa samples and five mucosa samples from control subjects were histopathologically analysed for dysplasia grade and tissue type, urokinase plasminogen activator levels and plasminogen activator inhibitor type 1 (PAI-1) using immunosorbent methods. Plasminogen activation and urokinase-mediated proteolytic activity levels were assessed using in situ zymography. Plasminogen activation and tissue-type activator levels were lower in adenomas than in mucosae (P < 0.001). PAI-1 concentration and urokinase levels were higher in adenomas than in mucosae (P < 0.001 and P < 0.001 respectively). In adenomas, urokinase concentration increased in parallel with PAI-1, but only the urokinase levels correlated with the dysplasia grade (P < 0.01). Thus, the alterations in plasminogen activation correlated with epithelial cell dysplasia grading. In the mucosa to adenoma transition, a marked decrease in tissue-type plasminogen activator occurred. In adenomas, this decrease was accompanied by a concomitant increase in urokinase and PAI-1. The urokinase level only continued to rise in parallel with the dysplasia grade. Resulting protease-antiprotease imbalance in high-grade dysplasia may represent the phenotypic change associated with malignant transformation and invasive behaviour.

New in Pathogenesis of Pertes Disease

The thesises detected do not allow to keep the pathogenesis of PD within the framework of the theory of primary vessels occlusion. In children with PD marked anomalies including the retardation of bone growth, increased rate of signs of general dysplasia of the connective tissue (detected also in near ralations - parents and siblings), changes of nondamaged contralateral head of the femur and spine, disturbance of glycosaminoglycane metabolism, asymmetric retardation of growth of different segments of the limbs. The authors believe that PD is the damage of femur associated with its overloading or another provocing factors that occur on the background of genetically substantiated defect with the damage of bone development. Further infarcts of the head of the femur develop repeatedly and independantly and thus the cupping of PD could be delayed. By the authors opinion PD could not be considerad as femur pathology in a normal child any more but rather as a local manifestation of the general skeleton dysplasia.

Value of p53 expression in oral cancer and adjacent normal mucosa in relation to the occurrence of multiple primary carcinomas.

Paraffin embedded, formalin fixed tissue sections from patients suffering from a primary oral squamous cell carcinoma were immunohistochemically investigated for the presence of p53 expression using the Bp53-11 antibody. The aim of this study was to determine the predictive value of p53 expression as a biomarker for the development of a second primary tumour (SPT) in the respiratory and upper digestive tract. In a nested case control study, neoplastic and normal tissue sections of 44 patients who had a previous history of cancer were used. 15 of the 44 had developed a SPT, while the other 29 were minimally 7 years free of disease. Additionally, nine SPTs were included in this study to establish whether concordance exists in tumours that develop in the same field. 10 of the 29 patients (34%) free of tumour during follow-up had p53 positive tumours. 8 of 15 patients (53%) who developed a SPT had a p53 positive primary tumour. This difference is not statistically different (chi 2-test). Forty percent of the total group of primary oral cavity tumours showed p53 positivity. When comparing the first and the second tumours, discordance in p53 expression between the first and second tumours was seen in 4 out of 9 cases. None of the cases showed p53 positivity in adjacent normal mucosa. In conclusion, p53 immunoreactivity in neoplasia, dysplasia and normal tissue does not predict the development of a SPT. In addition, multiple primary tumours do not have identical p53 expression.

Relationship between expression of epidermal growth factor and simian virus 40 T antigen in a line of transgenic mice

The pattern of expression of the simian virus 40 (SV40) T antigen gene and resultant dysplasia were re-examined in a line of transgenic mice in which the T antigen gene was under the control of the SV40 early promoter. We found that T antigen expression in the kidney, and resulting dysplastic lesions, occurred exclusively in the distal convoluted tubules and the ascending limbs of Henle. Epidermal growth factor (EGF) expression in the kidney of normal mice was similarly immunolocalized. The correlation between high EGF immunoreactivity in normal mouse tissues and T antigen expression in the transgenic counterpart was also seen in the choroid plexus epithelium and in the submandibular glands of male mice. T antigen was not found in the submandibular gland of transgenic females. Similarly, EGF was only rarely detected in the normal female submandibular gland. In contrast to the correlation between T antigen expression in the transgenic mice and EGF expression in the corresponding tissues of the normal mice, within the dysplastic lesions of the transgenic mice EGF expression was severely diminished. Adenocarcinomas of the male submandibular gland from another line of transgenic mice that expresses the Int-1 transgene, showed similarly reduced levels of immunostaining for EGF. Thus, reduced expression of EGF might be a general feature of dysplasia and tumorigenesis in those tissues that normally express EGF.

Follow-up after polypectomy: consensus?

Patients who have had a colorectal adenoma resected have an increased risk of subsequent cancer and may benefit from follow-up surveillance. Surveillance strategies should be tailored to the assessed risk of each individual patient. A number of long-term follow-up studies indicate that the risk of metachronous neoplasia is higher if on index colonoscopy there were multiple (> or = 2) adenomas, or if any adenoma was large (> or = 1 cm), contained villous tissue or severe dysplasia, or if the patient had a family history of colorectal neoplasia. Data from the U.S. National Polyp Study indicate that polyp resection and follow-up surveillance greatly reduces the incidence of metachronous cancer, and that the first follow-up colonoscopy does not need to be performed for 3 years. Current data have been incorporated into a comprehensive consensus practice guideline.

Unusual manifestations of craniofacial fibrous dysplasia: clinical, endocrinological and computed tomographic features

Clinical, endocrinological and computed tomographic features of three patients with unusual manifestations or complications of craniofacial involvement of fibrous dysplasia are presented. One patient with polyostotic fibrous dysplasia presented in late pregnancy with acute onset of bilateral optic nerve compression and blindness secondary to a rapidly expanding mass of fibrous dysplasia tissue involving the sphenoid, pituitary and optic chiasm regions. A second patient with polyostotic fibrous dysplasia developed thyrotoxicosis and probable gigantism/acromegaly in keeping with a rare form of McCune-Albright syndrome. Extensive bony distortion of the skull and facial bones by fibrous dysplasia made clinical recognition of these complications more difficult. A third patient had monostotic fibrous dysplasia with marked sclerosis of the sphenoid bone on plain radiographs which mimicked appearances of a meningioma and resulted in a negative craniotomy as computed tomography was not yet available at the time of presentation. Each case demonstrated rare complications of craniofacial fibrous dysplasia and highlighted the wide spectrum of appearances in which it may manifest, often resulting in overlap and diagnostic confusion with other disease processes. The value of computed tomography in assessment is emphasized.

Hemorrhage into fibrous dysplasia following minor head injury—Effective decompression for the ophthalmic artery and optic nerve

We performed an effective optic canal decompression in a patient with ethmoid and sphenoid fibrous dysplasia and visual impairment following minor head trauma. On admission, the patient's left visual acuity consisted only of light perception, and the left ophthalmic artery was not visible by angiography. A hematoma and fibrous dysplasia tissue in the sphenoid sinus were excised and the left optic canal was decompressed. The vision was markedly improved to an ability to count fingers in the following 2 weeks. The left ophthalmic artery was fully opacified in the postoperative angiogram.

Thrombospondin in milk, other breast secretions, and breast tissue.

Colostrum and milk contained high concentrations of thrombospondin, although the concentration relative to total protein content decreased as lactation was established. Thrombospondin occurred in the aqueous phase of milk rather than as a component of the milk fat globule membrane. It could be purified from colostrum using established procedures after removal of lipid from the starting material. The intact protein had a molecular weight of 450 kd, but the product contained small peptides, perhaps as a result of proteolytic activity in the colostrum. Thrombospondin from goat colostrum displayed a different proteolytic fragmentation pattern from thrombospondins isolated from three human sources, but this could be a species- rather than tissue-specific difference. Breast cancer cytosols contained significantly more thrombospondin than cytosols from normal tissue or benign dysplasias. Thrombospondin levels in a variety of breast secretions all fell within the range found in colostrum and milk, as did the fluids from Na+ (group II) breast cysts. K+ (group I) cysts, however, contained fluids with low thrombospondin concentrations, eliminating apocrine cells as the source of thrombospondin in the breast.

Intracranial Multiple Berry Aneurysms associated with Fibromuscular Dysplasia and Mixed Connective Tissue Disease

A rare case of multiple intracranial berry aneurysms associated with fibromuscular dysplasia (FMD) and mixed connective tissue disease (MCTD) is reported together with a review of the literature, particularly that of Japan. The patient was a 59-year-old woman who had a subarachnoid hemorrhage during the course of MCTD. Angiographically, multiple intracranial aneurysms and “string of beads” were demonstrated in both cervical internal carotid arteries. The three aneurysms of the left internal carotid and middle cerebral arteries were treated surgically, and the remaining aneurysms in the right middle cerebral artery and at the top of the basilar artery were to be treated at a later date. Although the immediate postoperative course was uneventful, 1 month after surgery the patient died suddenly of sepsis with disseminated intravascular coagulation. At autopsy, FMD involving medial fibroplasia with aneurysms was found in the internal carotid and renal arteries. The intracranial aneurysms showed features typical of saccular aneurysms related to the arterial fork. Other than the aneurysms, no changes due to FMD were noted in the cerebral arteries. Although characteristic MCTD lesions were present in the visceral organs, no specific changes due to MCTD were seen in the brain. Among the 29 patients with cervico-cephalic FMD reported in Japan, 15 had intracranial aneurysms. These included four cases of multiple aneurysms and 11 cases of rupture. No association between FMD and MCTD has been reported in the world literature.

MR Imaging of the Breast Using Gadolinium-DTPA

In a preliminary study 20 patients underwent breast examinations by magnetic resonance (MR) imaging without and with Gd-DTPA as contrast medium. All carcinomas enhanced, whereas dysplastic tissue enhanced slightly or not at all. Significant additional diagnostic information was available on the Gd-DTPA examinations in at least four of 20 cases compared with MR without contrast medium and X-ray mammography. Our preliminary results indicate that MR imaging of breast using Gd-DTPA may be helpful for the evaluation of dense breasts and the differentiation of dysplasia and scar tissue from carcinoma.

Familial intracranial aneurysms: Report of four families

The authors describe eight cases of familial intracranial aneurysms occurring in four families. In the literature reviewed, familial aneurysms have different characteristics in that the incidence of the anterior communicating aneurysms is lower and that of the middle cerebral aneurysms is somewhat higher, and the age of patients at diagnosis is often younger. Although the number of patients is few, our study does not support these characteristics. A family history of intracranial aneurysms should include such high-risk factors as polycystic kidneys, coarctation of the aorta, fibromuscular dysplasia, and other connective tissue disorders.

Long-term follow-up study on gastric adenoma and its relation to gastric protruded carcinoma.

A total of 191 gastric adenomas in 178 patients was studied macroscopically by endoscopy and histopathologically by endoscopic biopsy. Among the lesions, 85 in 74 patients were followed-up for six months to 12 years. Gastric adenomas were found to be more frequent in the aged, with a rate of 0.1% in the third decade but 3.7% in the ninth decade, on gastroscopic examination. Gastric cancers coexistent with the gastric adenomas were seen in 14 cases (8%), and were more frequent in male than in female patients (sex ratio, 12:2). Only eight of the 85 lesions (9%) revealed macroscopic changes. Four of these showed a reduction in size, while the other four lesions showed enlargement. In 21 of the 85 lesions (25%), histologic changes were observed. Four (5%) changed from moderate dysplasia (Group III) to nondysplastic or intestinal metaplasia (Group I), eight lesions (9%) revealed histologic changes (Group III to IV, or vice versa) without malignant transformation, and nine lesions (11%) showed malignant changes. Neither submucosal invasion nor lymph node metastasis was found. These lesions consisted of carcinoma in situ with small foci in the lesions exhibiting moderate dysplasia, and a gradual transition from severe dysplasia to cancer was seen in resected lesions obtained by endoscopic polypectomy or surgical resection. In addition, a gradual increase in dysplasia of tissue from moderate to severe was revealed by repeated gastroscopic biopsy. These findings suggest that the gastric adenomas underwent malignant changes with gradual transformation from moderate through severe dysplasia.

Genetic Diseases in Pregnancy: Maternal Effects and Fetal Outcome

ABSTRACT Health professionals involved in perinatal care find increasing difficulty keeping pace with the burgeoning of scientific, clinical, and biotechnological information related to genetic and hereditable disorders. Thus, there has been real need for a succinct, lucid, comprehensive summary of such information relevant to perinatal care.Genetic Diseases in Pregnancy fills a long-awaited need. It is a timely, well-organized, readable miniencyclopedia of genetic diseases in pregnancy. In its 13 chapters, this volume covers selected metabolic diseases; disorders of connective tissue and skeletal dysplasia; hemoglobinopathies; Rh and other blood group incompatibilities; genetic disorders of hemostasis; defects of the cardiovascular, respiratory, renal, and gastrointestinal systems; diabetes mellitus; endocrine aspects of genetic disorders in pregnancy; chromosomal abnormalities; and genetic counseling and the major psychiatric disorders. This text covers the maternal effects and fetal outcome related to the foregoing subjects. Emphasis is placed on clinical manifestations of the genetic disorders, on diagnostic screening recommendations, on

Etiology of scoliosis in children

The morphology of paravertebral muscles biopsied from 5 patients with scoliosis, as well as muscles autopsied from 35 corpses of newborns and children who died from accidental causes and had no signs of scoliosis, was studied. The asymmetry of the structure of paravertebral muscles in newborns and children, caused by congenital dysplasia of muscle tissue, was found. This asymmetry can be considered as an etiological factor in the onset of scoliosis.

Radiological and pathological aspects of tuberous sclerosis with special reference to hydrocephalus

Summary Two cases of tuberous sclerosis, both complicated by hydrocephalus, are presented with a report of the clinical, radiological, and autopsy findings. The radiological findings previously recorded in tuberous sclerosis are reviewed, and the relationship of the radiological to the pathological lesions examined. The generalized nature of the disease and its protean clinical and radiological manifestations are emphasized. Radiological and pathological evidence is offered to suggest that tuberous sclerosis should be regarded as a widespread dysplasia of both mesodermal and ectodermal tissues.