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PubMed2005

Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues.

Relatively few attempts have been made in the past to isolate and expand lymphatic endothelial cells (LECs). Recently this task has become feasible thanks to the identification of new lymphatic markers such as Podoplanin, Lyve-1, Prox-1 and D2-40. Using a two-step purification method based on the sorting of endothelial cells with Ulex Europaeus Agglutinin 1-coated beads followed by purification with monoclonal antibody D2-40, we were able to purify and in vitro expand human derived LECs from tissues such as lymph node, spleen, thymus, palatine tonsil and iliac lymphatic vessels. The isolated LECs were expanded on collagen type 1 and fibronectin coated flasks for up to 8-10 passages and then analyzed for phenotypic and functional properties. LECs were able to form a capillary like network, when seeded on Cultrex BME, indicating their capability to form lymphatic vessels in vitro. Comparative studies were performed, and we found that specific lymphatic and vascular markers were differentially expressed by LECs prepared from different sources, clearly demonstrating the phenotypic heterogeneity of LECs from different organs and different segments of the lymphatic vasculature. We here propose a new technique to make available ready sources of abundant well-characterized human LECs to examine normal profiles and behavior to compare with abnormal conditions.

Biomarkers↗
PubMed1994

Two novel human B-cell lymphoma lines of lymphatic follicle origin: cytogenetic, molecular genetic and histopathological characterisation.

Two B-cell lines, designated as HF-1 and HF-4, were characterised. The cell lines have complicated karyotype abnormalities including a 14;18 translocation and an 8q24 breakpoint originating from t(2;8)(p11;q24) (HF-1) or t(1;8)(p21;q24) (HF-4). The lines have BCL2 rearrangement and they are positive for CD19, CD20, CD22, CD39. HF-1 is also positive for IgG, and HF-4 is positive for IgM and IgD. On Northern blot analyses, the 2.6-kb and 4.2-kb transcripts corresponding to the major transcripts of CMYC and BCL2, respectively, were seen. In Western blot as well as in FACS (fluorescence-activated cell sorting) analysis the presence of BCL2 protein in the both HF-1 and HF-4 cells was demonstrated. The cell lines are expected to serve as an important tool in the study of the chromosomal mechanism activating cellular oncogenes, the somatic hypermutation mechanism of antigen-activated B cells and the apoptosis of B cells.

Base Sequence↗
PubMed1987

[Chronic venous insufficiency and microcirculation. Physiopathologic and therapeutic reflections].

In patients with chronic venous insufficiency, tissular damage occurs as a consequence of microcirculatory disturbances. Venular distension, venulo-arteriolar reflex and probably valves in collecting venules are the only microcirculatory protective mechanisms against venous pressure overload. Edema is primarily a consequence of increased capillary hydrostatic pressure. However, the increase of endothelial macromolecular transport and a true lymphatic microangiopathy are important contributive factors. Venous ulceration is hypoxic although the amount of total blood flow is normal in the surrounding tissue. Several hypothesis were proposed for explaining this nutritional steal: arterio-venous shunt vessels have never been shown consistently, peri-capillary fibrin deposition might block oxygen diffusion, and last but not least, the abnormal geometrical arrangement of the capillary bed is facilitating functional shunting. On a therapeutic point of view, behind the classical hemodynamic therapy, the microvascular approach to chronic venous insufficiency supports the use of lymphatic manual drainage for controlling edema and rheologic therapy for improving skin capillary perfusion.

Humans↗
PubMed1990

Cytogenetics in the investigation of haematological disorders.

Chronic and acute, myeloid and lymphatic haematological neoplasms are characterized by acquired genetic rearrangements that, in the majority of cases, can be detected as clonal chromosomal abnormalities. The aberrations are either primary, meaning that they contribute to the establishment of the neoplasm, or secondary, in which case they are acquired during the clonal evolution and malignization of the neoplastic cells. The abnormalities are non-randomly distributed; the aberration pattern differs from disease to disease and sometimes is so characteristic that individual rearrangements may be virtually pathognomonic for particular neoplasms. The cytogenetic characterization of haematological malignancies is of two-fold importance. First, the recurrent aberrations provide us with an insight into the pathogenetic mechanisms that are operative. They pinpoint those areas of the human genome that carry genes or regulatory sequences whose function is disturbed in leukaemias and lymphomas. Using DNA recombinant techniques in addition to chromosome-level investigations of these cancer-associated rearrangements, the molecular pathology of leukaemias and lymphomas is now gradually being unravelled. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have a direct clinical importance. The finding of an acquired, clonal chromosome abnormality in haematopoietic cells (-Y in old men is an exception) means that the patient has a neoplastic disease. Often, but by no means always, the type of aberration is also informative as to which type of neoplasm is present. During therapy, remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern influences prognosis and may thus be taken into account when the choice of therapy is made.

Chromosome Aberrations↗
PubMed1999

Xeroderma pigmentosum in Libya.

BACKGROUND: A preliminary study of 24 cases of xeroderma pigmentosum (XP) was presented in 1990 and later published in 1992. Since then we have seen 18 further cases. OBJECTIVE: To study the clinical profile of Libyan cases of XP. METHODS: With the help of a special protocol, all 42 cases (23 girls and 19 boys from 29 families) treated and followed between 1981 and 1994 were subjected to detailed analysis. RESULTS: A history of consanguinity was present in the parents of 39 patients. XP in Libya is characterized by a relatively high incidence (approximately 15-20 per million of the population), early onset of initial manifestations (median age, 12 months) and malignant tumors (median age, 8 years), severe ocular and oral lesions in a high percentage of patients, and early death (median age, 15.5 years). The malignant skin tumors seen were squamous cell carcinoma (SCC) in 23 patients, basal cell carcinoma (BCC) in 17 patients, and basosquamous carcinoma in two patients. Malignant melanoma was not seen, but lentigo maligna was found in one case. SCC of the tongue, carcinoma of the thyroid, and lymphatic leukemia affected individual patients. Subnormal physical growth was observed in six patients, but none of the patients had significant neurologic abnormalities. The results of etretinate therapy in nine patients revealed that it is an effective preventive agent against carcinogenesis, but not a curative one. CONCLUSIONS: Severe ophthalmic manifestations affected a higher percentage of patients at an early age. Malignant melanoma did not develop in any case, except for lentigo maligna in one patient.

Age of Onset↗
PubMed1996

Early diagnosis of low grade malignant lymphoma and chronic lymphocytic leukaemia. Verification of morphologically suspected malignancy in blood lymphocytes by flow cytometry.

According to international recommendations, the diagnosis of chronic lymphocytic leukaemia (CLL) is made on the grounds of persistent peripheral lymphocytosis or lymphocytic infiltration of the bone marrow. The appearance of morphologically atypical lymphocytes in low-grade malignant lymphoma (NHL) or CLL is easily overlooked, and is generally not regarded as a diagnostic criterion. We report 12 cases of CLL/NHL who were detected only by morphological screening of routine peripheral blood smears (83,400 blood smears). The diagnosis of CLL/NHL was not suggested by the patients' history, physical or other laboratory findings, and had not been contemplated by the physician in charge. Monoclonality of peripheral lymphocytes was confirmed by immunophenotyping and Southern blotting. The lymphoma was classified histologically according to the International Working Formulation (bone marrow biopsy). A monoclonal lymphatic population was not found by immunophenotyping in the blood of 11 patients whose lymphocytes were morphologically classified as activated-abnormal. However, 3 patients suspected to have NHL/CLL on morphological screening of blood smears had to be classified as benign after immunophenotyping. We conclude that morphological screening of routine blood smears is an inexpensive and easy additional screening method for CLL and low grade malignant NHL.

Aged↗
PubMed2004

Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is still the gold-standard therapy for pulmonary alveolar proteinosis (PAP). The few studies on the duration of the effect of WLL, belonging to a rather remote period, show significant but transient benefits. In 21 patients with idiopathic PAP, the duration of any benefit and, in 16 of them, the time course of lung function improvement (at baseline, 1 week, 6 months, 1 yr and then every 2 yrs after WLL) were evaluated. The present WLL technique takes longer, is invasively monitored and partially modified with respect to past techniques. More than 70% of patients remained free from recurrent PAP at 7 yrs. The bulk of the improvement in spirometric results was almost completely gained in the immediate post-WLL period due to the efficient clearance of the alveoli. At a median of 5 yrs, recovery of diffusing capacity of the lung for carbon monoxide was incomplete (75 +/- 19% of the predicted value) and there were residual gas exchange abnormalities (alveolar to arterial oxygen tension difference 3.6 +/- 1.5 kPa (27 +/- 11 mmHg)) and exercise limitation, probably explained by engorgement of lymphatic vessels. In conclusion, whole lung lavage for idiopathic pulmonary alveolar proteinosis is currently a safe procedure in an experienced setting, and provides long-lasting benefits in the majority of patients.

Adolescent↗
PubMed1993

Value of CT in determining the resectability of hepatoblastoma before and after chemotherapy.

OBJECTIVE: The purpose of this study was to assess the accuracy of CT for determining surgical resectability of hepatoblastoma before and after chemotherapy. MATERIALS AND METHODS: Preoperative and postoperative CT scans of 15 children with surgically confirmed hepatoblastoma were retrospectively reviewed and correlated with surgical findings and pathologic analysis. RESULTS: Before chemotherapy, 12 of the 15 children had unresectable tumors because of bilobar involvement, metastatic disease, or vascular extension. After chemotherapy, tumor volumes decreased by 20-98%, with increased areas of low attenuation and calcification. Periportal areas of low attenuation (four of nine), abdominal adenopathy (four of four), and lung nodules (four of six) disappeared after chemotherapy. On the basis of CT and clinical findings, all tumors were thought to be resectable. Surgical correlation showed that the extent of hepatic tumor had been overestimated on immediate preoperative CT scans in three children (tumor was staged as bilobar, but only single-lobe resection was required). Correlation between areas of low attenuation in the tumor and necrosis in pathologic specimens was poor. Tumor invasion of periportal lymphatics was seen in one of five children with periportal areas of low attenuation. Postoperatively, five of 13 children had CT abnormalities, three at the resection margins with calcification, low attenuation, or both. Hepatic or abdominal disease has not recurred, and 12 of the 14 children who survived surgery are well. One child who had abnormal findings on preoperative chest CT died of pulmonary metastases. Another in whom chemotherapy was limited because of toxic effects died after tumor recurred in the liver. CONCLUSION: Pretreatment CT scans cannot be used to predict ultimate resectability of hepatic tumors; nor are preoperative scans always accurate for judging exact lobar involvement. Absence of disease as shown on CT scans correlated with absence both at surgery and at follow-up. Postoperative hepatic changes are common and do not necessarily reflect recurrent or residual tumor.

Carcinoma, Hepatocellular↗
PubMed2002

Primary cutaneous alveolar rhabdomyosarcoma of the perineum.

Primary alveolar rhabdomyosarcoma (RMS) involving perineal skin is extremely rare, particularly in the infant age group. We report a case of an alveolar RMS in a newborn with abnormal symmetrical perineal overgrowth, causing ambiguous morphologic structure of the genitalia. Clinical and imaging studies were suggestive of Proteus syndrome with lymphatic malformation. Histologic examination of the mass showed cutaneous alveolar RMS with areas of embryonal and pleomorphic RMS features. Multiple superficially located, cystic-dilated spaces with loose edematous-mucoid hypocellular stroma gave a gross morphologic structure similar to that of lymphatic-type excrescences.

Female↗
PubMed1987

Prenatal sonographic diagnosis of isolated congenital cystic hygroma, unassociated with lymphedema or other morphologic abnormality.

We report the prenatal sonographic diagnosis of five cases of isolated cystic hygroma (lymphangioma), unassociated with lymphedema or other morphological abnormalities. This type of cystic hygroma appears different from the ones occurring at the back of the neck, which have other lymphatic anomalies and a poor prognosis. Four of the five fetuses did well after surgery. We describe the sonographic appearance of this type of cystic hygroma, which is different from the nuchal type as it is primarily complex.

Edema↗
PubMed1993

Thoracic lymph node metastasis and carcinomatous lymphangitis after inoculation of Walker 256 tumor through the trachea.

1. Experimental models of carcinomatous lymphangitis have not been described. This is an important clinical entity which usually results in the patients' death, although its natural history is still controversial. This study was undertaken to investigate whether the pattern of lung involvement after Walker 256 tumor inoculation through the trachea is a good model of carcinomatous lymphangitis. 2. Fifty male Wistar rats were inoculated through the trachea with 2.5 x 10(6) Walker 256 tumor cells and killed in groups of 5 animals each at 6 h and on days 1, 3, 7, 14, 21, 28, 35, 45, and 60 of the experiment. The lungs and thoracic lymph nodes were examined by light microscopy. 3. There were no tumors in the 25 animals killed before the 21st day of the experiment. The remaining 25 rats were sacrificed after 3 weeks of the experiment; 52% of them displayed thoracic lymph node metastases, and 40% developed a mild carcinomatous lymphangitis. The lung involvement did not correlate with respiratory distress, tumor dissemination or additional histological abnormalities. 4. We conclude that invasion of the lung is possible after intratracheal tumor cell inoculation, and that spreading follows a lymphatic pattern. This finding establishes this approach as a viable experimental model of carcinomatous lymphangitis. New approaches to increase the intensity and frequency of lung involvement, as well as the development of respiratory distress should be pursued in order to improve the efficiency of this model.

Animals↗
PubMedDate not supplied

[Sudden hearing loss and uveitis as a form of presentation of neurosarcoidosis].

Sarcoidosis is a multisystem granulomatous disease of unknown cause with frequent pulmonary, ocular, and lymphatic system manifestations. Central nervous system involvement, although rare (1 to 5%), most commonly affects the cranial nerves. Cranial nerve VIII abnormalities occur in 20% of these patients and are associated with other neuropathies and organ or system involvement. We report a case of neurosarcoidosis that presented as isolated sudden sensorineural hearing loss and uveitis.

Adolescent↗
PubMed2006

Cervical lymphadenopathy in children--incidence and diagnostic management.

OBJECTIVE: Palpable lymph nodes are common due to the reactive hyperplasia of lymphatic tissue mainly connected with local inflammatory process. Differential diagnosis of persistent nodular change on the neck is different in children, due to higher incidence of congenital abnormalities and infectious diseases and relative rarity of malignancies in that age group. The aim of our study was to analyse the most common causes of childhood cervical lymphadenopathy and determine of management guidelines on the basis of clinical examination and ultrasonographic evaluation. MATERIAL AND METHODS: The research covered 87 children with cervical lymphadenopathy. Age, gender and accompanying diseases of the patients were assessed. All the patients were diagnosed radiologically on the basis of ultrasonographic evaluation. RESULTS: Reactive inflammatory changes of bacterial origin were observed in 50 children (57.5%). Fever was the most common general symptom accompanying lymphadenopathy and was observed in 21 cases (24.1%). The ultrasonographic evaluation revealed oval-shaped lymph nodes with the domination of long axis in 78 patients (89.66%). The proper width of hilus and their proper vascularization were observed in 75 children (86.2%). Some additional clinical and laboratory tests were needed in the patients with abnormal sonographic image. CONCLUSIONS: Ultrasonographic imaging is extremely helpful in diagnostics, differentiation and following the treatment of childhood lymphadenopathy. Failure of regression after 4-6 weeks might be an indication for a diagnostic biopsy.

Abscess↗
PubMed1997

Unusual miliary tuberculosis presenting with generalized lymphadenopathy and abdominal involvement.

Although tuberculosis is common and well recognised in many countries, unusual presentations of the disease sometimes raise difficulties in differential diagnosis. We report a young patient who presented with weight loss, shortness of breath and easy fatiguability. Extensive lymphadenopathy involving the cervical, axillary and inguinal regions were found on physical examination. Chest X-ray and computed tomography revealed generalized lymphadenopathy of cervical, mediastinal and para-aortic chains, bilateral pulmonary miliary reticulonodular infiltrates, pleural effusion, hepatomegaly with low density, macronodular hypodense areas in spleen, ascites, peritoneal irregularity and thickening of bowel walls. Mantoux test was negative. Peritoneal fluid was exudative, but pleural fluid was transudative, probably due to mediastinal lymphatic obstruction. The initial clinical diagnosis was malignant lymphoma; however, positive sputum smears for mycobacteria and excisional cervical lymph node biopsy revealing caseating granulomatous lymphadenitis were consistent with tuberculosis. The patient responded well to appropriate therapy with regression of radiological abnormalities.

Adult↗
PubMed2006

Solitary superficial microcystic lymphatic malformation (lymphangioma circumscriptum) of the gingiva.

BACKGROUND: Lymphatic malformations are uncommon, hamartomatous, developmental aberrations of the lymphatic system. The case presented in this report is a rare solitary gingival involvement of a microcystic-type lymphatic malformation. METHODS: The lesion presented clinically as a small vesicular swelling of a buccal interdental papilla in a 16-year-old girl. Involved tissues were excised and submitted for routine histologic examination. The expression of the endothelial marker CD34 was investigated using immunohistochemical staining. RESULTS: A physical examination failed to reveal similar or other abnormalities elsewhere in the body of the patient, including the oral cavity. Histopathologic analysis of the specimen demonstrated the presence of subepithelial, thin-walled, distended vascular cavities forming confluent vesicles containing lymph. The dilated lymphatic formations were lined by flattened CD34-negative endothelial cells. These features were consistent with a microcystic gingival lymphatic malformation. To the best of our knowledge, only two additional reports of this malformation have been published to date, but both presented with bilateral gingival involvement. CONCLUSION: Even though lymphatic malformations are encountered very infrequently on gingiva, they should be considered in the differential diagnosis of related conditions with a vesicular clinical appearance.

Adolescent↗