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Electrophoretic analyses in a case of monoclonal gamma chain disease.

Abnormal low molecular weight immunoglobulin heavy chain can be detected in serum samples from patients with heavy chain disease. In this paper, we report the characterization of a gamma heavy chain in a patient suffering from a lymphoplasmocytic disorder, using immunofixation analysis and two-dimensional polyacrylamide gel electrophoresis. We demonstrate that the combination of serum protein agarose electrophoresis and two-dimensional electrophoresis (three-dimensional electrophoresis) can be used to further characterize abnormal protein bands detected by immunofixation.

Electrophoresis, Gel, Two-Dimensional↗

Technical description of endoscopic ultrasonography with fine-needle aspiration for the staging of lung cancer.

BACKGROUND: Endoscopic ultrasonography (EUS) is a novel method for staging of the mediastinum in lung cancer patients. The recent development of linear scanners enables safe and accurate fine-needle aspiration (FNA) of mediastinal and upper abdominal structures under real-time ultrasound guidance. However, various methods and equipment for mediastinal EUS-FNA are being used throughout the world, and a detailed description of the procedures is lacking. A thorough description of linear EUS-FNA is needed. METHODS: A step-by-step description of the linear EUS-FNA procedure as performed in our hospital will be provided. Ultrasonographic landmarks will be shown on images. The procedure will be related to published literature, with a systematic literature search. RESULTS: EUS-FNA is an outpatient procedure under conscious sedation. The typical linear EUS-FNA procedure starts with examination of the retroperitoneal area. After this, systematic scanning of the mediastinum is performed at intervals of 1-2cm. Abnormalities are noted, and FNA of the abnormalities can be performed. Specimens are assessed for cellularity on-site. The entire procedure takes 45-60 min. CONCLUSIONS: EUS-FNA is minimally invasive, accurate, and fast. Anatomical areas can be reached that are inaccessible for cervical mediastinoscopy. EUS-FNA is useful for the staging of lung cancer or the assessment and diagnosis of abnormalities in the posterior mediastinum.

Biopsy, Fine-Needle↗

Proliferation of CD3+ B220- single-positive normal T cells was suppressed in B-cell-deficient lpr mice.

It is known that lpr mice develop systemic lymphadenopathy and lupus erythematosus-like autoimmune disease that are associated with the accumulation of CD4- CD8- (double-negative; DN) CD3+ B220+ abnormal T cells as well as normal mature CD4+ or CD8+ single-positive (SP) CD3+ T cells. In order to clarify the role of B cells in the lymphoproliferation and autoimmunity of lpr mice, we created B-cell-deficient C57BL/6 (B6) lpr mice (B6lpr/lpr microMT/microMT) by crossing B6lpr/lpr mice with B6 microMT/microMT mice in which the B-cell development was arrested at pre-B stage owing to a targeted disruption of the immunoglobulin mu heavy-chain gene locus. In the B-cell-deficient B6-lpr mice, both lymphadenopathy and splenomegaly were markedly suppressed. Although the accumulation of both CD3+ B220- SP normal T cells and CD3+ B220+ DN abnormal T cells was inhibited in the B-cell-deficient lpr mice, the decrease in numbers of CD3+ B220- SP normal T cells occurred more strikingly than that of the CD3+ B220+ DN abnormal T cells. Glomerulonephritis did not develop in the B-cell-deficient lpr mice over 40 weeks. The present results indicate that the B cells thus play a crucial role in the extensive proliferation of normal CD3+ B220- mature SP T cells rather than the accumulation of abnormal DN T cells.

Animals↗

Leucopenia, thrombocytopenia and lymphadenopathy associated with sulphasalazine.

We report a 19-year-old woman with psoriasis who developed a severe allergic reaction within 1 week of commencement of sulphasalazine; her skin becoming erythrodermic with associated lymphadenopathy, leucopenia and thrombocytopenia. Clinical signs and haematological abnormalities rapidly returned to normal on discontinuation of sulphasalazine. It is important to monitor carefully haematological indices in the early stages of treatment with this drug.

Adult↗

Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa.

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.

Adenocarcinoma↗

Splenomegaly at a university hospital compared to a nearby county hospital in 317 patients.

Splenomegaly and massive splenomegaly were diagnostically evaluated retrospectively at Stanford University Hospital in 147 patients over 8 years and compared to the nearby county hospital (Santa Clara Valley Medical Center; VMC) in 170 inpatients over 11 years. Hematologic diseases at Stanford (data for VMC in parentheses) occurred in 66% (35%; p < 0.001) of the patients with splenomegaly and in 84% (54%; p < 0.001) of those with massive splenomegaly. Hepatic diseases occurred in 9% (36%; p < 0.001) of the patients with splenomegaly and in 5% (29%; p < 0.001) of those with massive splenomegaly. Splenectomy was performed in 71% of the patients at Stanford and in 9% of those at VMC (p < 0.001). The combined Stanford-VMC series showed significant associations (p < 0.01): for hematologic diseases with massive splenomegaly, lymphadenopathy, and blood cytoses; for hepatic diseases with hepatomegaly, cytopenias as hypersplenism, and abnormal liver function tests, and for infectious diseases with fever.

Adolescent↗

Progressive lymphangiectasis and recurrent chylothorax in a dog after thoracic duct ligation.

A 2-year-old Bernese Mountain Dog was examined to determine the cause of bilateral pleural effusion. Torsion was diagnosed, and a lobectomy of a lung lobe was performed. Chylothorax developed 12 days after lung lobectomy. Mesenteric lymphangiography revealed lymphangiectasis Lymphangiography immediately after surgical thoracic duct was completely obstructed, but chylothorax persisted after thoracic duct ligation. Lymphangiography was repeated 50 days after ligation of the thoracic duct and revealed multiple patent thoracic duct branches and progressive lymphangiectasis. A second attempt to ligate the thoracic duct caused the effusion to become serosanguineous. A pleuroperitoneal shunt with a manually operated pump chamber was used to remove the pleural effusion. Chylothorax was again detected 50 weeks after placement of shunt. Mesenteric lymphangiography revealed multiple patent thoracic duct branches and a lymphatic plexus that extended across the thoracic cavity.

Animals↗

Omenn's reticulosis associated with the nephrotic syndrome.

Omenn's reticulosis is an inherited severe combined immunodeficiency characterized by neonatal exfoliative erythroderma. A newborn baby who had minimal change nephrotic syndrome and Omenn's reticulosis is reported. Abnormalities in lymphocyte function could explain both the nephropathy and the cutaneous changes.

Dermatitis, Exfoliative↗

Antenatal diagnosis and obstetric management of cystic hygroma occurring in twin pregnancies. A case report.

The lymphatic system has an early development in the embryo. Usually, its development is complete by the 40th postconceptional day. If this connection fails to develop, lymphatic stasis and dilatation of the lymphatic channels may occur, causing a number of pathologies such as: lymphangiomas, lymphangiectasis and cystic hygromas. Prenatal diagnosis can be made during the first trimester of pregnancy by ultrasonographic examination. A case of a twin pregnancy associated with cystic hygroma and bilateral hypoplasia of lower and upper limbs of both foetuses without chromosomal abnormalities is reported.

Adult↗

A model of the factors affecting interstitial volume in oedema. Part II: Their effects at various abnormal steady-states.

A mathematical model has been used to investigate the alterations, in amount and importance, of the Factors controlling interstitial fluid volume in a number of steady-state oedemas. Steady-states were used because it is much easier to evaluate the effect of a specific Factor on oedema if all the others are constant. They are best compared if expressed in the same units: ml/min/100 g of tissue. The effects of lymphatic drainage on trauma are very important, as is the effect of tissue proteolysis on lymphoedema. Tissue proteolysis has minimal effects on the normal state and trauma; yet modelling its increase with benzo-pyrones markedly reduces oedema in both trauma and lymphoedema. Excess fibrosis greatly reduces lymphoedema. The effects of the individual Factors vary considerably between the different steady-states.

Edema↗

Cytogenetics of a case of eccrine spiradenoma.

A cytogenetic study of an eccrine spiradenoma and two lymph node metastases, with a growth pattern and microscopic appearance typical for benign eccrine spiradenoma, revealed a 46,XY-5,del(16)(q22),+mar(t(?;5)(?::5q13----5qter)) karyotype. The finding of the same abnormal karyotype in the tumor and the metastases suggests a relationship between the chromosomal abnormalities and the clinical malignant behavior of this morphologic benign tumor.

Adenoma, Sweat Gland↗

Bone scintigraphy in nasopharyngeal carcinoma.

One hundred and forty-three patients (Group 1) with histologically proven nasopharyngeal-carcinoma (NPC) had bone scintigraphy with 99Tcm methylenediphosphonate (MDP) or dihydroxypropanediphosphonate (DPD) within 2 months of the initial diagnosis. A further 162 patients (Group 2) had bone scans during the course of follow-up if there were symptoms of bone pain or evidence of metastases at other sites. Twenty-three per cent (33/143) of the newly diagnosed NPC patients (Group 1) had evidence of bone metastases. Of these 143 patients, 101 were T0-T2, 16 were T3 and 25 were T4. Thirty-six patients had no neck nodes (NO), 44 were N1, 25 N2 and 38 N3. Of the 162 patients in Group 2, 96 (59%) had a positive bone scan. The commonest sites for bony metastases from NPC were the spine, ribs, pelvis and lower limbs in order of frequency. There is a highly significant association with the nodal stage but no association with the UICC T staging which is not adequate in nasopharyngeal carcinoma. In our part of the world, bone metastases from NPC are a common cause of an abnormal bone scan.

Adolescent↗

Potential roles of follicular dendritic cell-associated osteopontin in lymphoid follicle pathology and repair and in B cell regulation in HIV-1 and SIV infection.

Osteopontin is a multifunctional protein with known roles in bone remodeling, wound healing, and normal and pathological immune responses. We showed in microarray studies that osteopontin gene expression is increased in human immunodeficiency virus type 1 (HIV-1)-infected lymphatic tissues after treatment, and we undertook mapping experiments to study osteopontin's possible functions in this context. We discovered species-specific colocalization of osteopontin with the follicular dendritic cell (FDC) network in lymphatic tissues in HIV-1 and simian immunodeficiency virus infections, and we found that changes in FDC-associated osteopontin covary with changes in lymphoid follicles during acute and late stages of infection and in response to treatment. We propose that this localization normally facilitates antibody production and plays a role in B cell abnormalities in infection and in the reconstitution of lymphoid follicles with treatment and that mapping genes identified in microarray studies is a useful experimental approach to gaining a better understanding of function in the context of a particular tissue and disease.

Animals↗

Vagal paragangliomas: a clinical, pathological, and DNA assessment.

Ten vagal paragangliomas were studied by image analysis and the results correlated with clinicopathologic features to determine if the DNA ploidy pattern could be used to separate benign from malignant paragangliomas. The tumours occurred in 8 women and 2 men ranging in age from 23 to 75 years (average 54 years). Follow-up was available in all 10 patients and ranged from 3 months to 27 years (average 7.8 years). Of the 10 tumours examined for DNA, 5 were diploid, 4 diploid-tetraploid, and 1 aneuploid. Two patients experienced local recurrences. One of these had a diploid tumour that recurred 22 years after excision and the other had an aneuploid tumour which recurred 4 years 4 months later and was associated with cervical lymph node metastasis. Two patients had malignant tumours with histologically confirmed metastases to noncontiguous cervical lymph nodes. One of the malignant tumours was diploid and the other aneuploid. This study concludes that DNA abnormalities are common in vagal paragangliomas and that tumour ploidy can not be used to assess malignant potential.

Adult↗

T-cell subset analysis by monoclonal antibodies in primary immunodeficiencies.

T-cell subsets have been analysed in 23 cases of primary immunodeficiency with monoclonal antibodies. Functional assays investigating T-cell function--proliferative response to mitogens, antigens, and allogeneic cells, cytotoxicity generated against allogeneic target cells and helper function to pokeweek mitogen-induced immunoglobulin synthesis--were performed in parallel in the same patients. The results enabled us to delineate four groups of patients. The first group consisted of patients in whom marker and function studies show concordant data, with either normal or strongly decreased T-cell number and function. The second group consisted of patients in whom various degrees of functional abnormality coexist with subnormal T-cell number and increased suppressor T-cell proportion. In the third group, we collected all patients who showed functional deficiencies without marker abnormalities. Finally, there was a small group composed of patients whose T-cell pattern was strongly suggestive of abnormal differentiation.

Adenosine Deaminase↗

Neuropathy associated with lymphoma.

Electrophysiological studies have been performed on 62 subjects with malignant lymphoma and the results compared with those of 35 control subjects matched for age. There was evidence of impairment of conduction consistent with a generalized peripheral neuropathy in 22 subjects (35%). Histological and electronmicroscopic studies were performed on sural nerve biopsy material from five subjects, and the pathological abnormalities of the myelinated fibres were those of axonal degeneration and segmental demyelination. The unmyelinated fibres were not affected.

Action Potentials↗

Breast cancer in patients irradiated for Hodgkin's disease: a clinical and pathologic analysis of 45 events in 37 patients.

PURPOSE: To characterize the clinical and pathologic features of patients who developed breast cancer (BC) after treatment for Hodgkin's disease (HD). Recent epidemiologic studies have shown that women who are cured of HD have an increased risk of developing BC. PATIENTS AND METHODS: The clinical data, mammograms, and pathologic specimens of 37 women who developed 45 BCs (eight bilateral events), and had a prior history of treatment for HD were analyzed. RESULTS: The median age at diagnosis of HD was 27 years (range, 11 to 60). All patients received radiotherapy (RT) to the upper part of their body, and 10 also had chemotherapy for HD. The median interval from the treatment of HD to the diagnosis of BC was 15 years (range, 8 to 34). The median age at diagnosis of BC was 43 years (range, 27 to 75), 41% of patients were 39 years old or younger. Most mammograms (81%) showed abnormal findings of mass and/or microcalcifications. Of the eight patients (22%) with bilateral tumors, four were synchronous and four were metachronous. Involvement of the medial half of the breast occurred more frequently than in patients with primary BC (39% and 21%, respectively; P < .002). But, the histologic types, grades, presence of lymphocytic reaction, and lymphatic invasion were similar to those observed in 935 primary BC patients who were previously analyzed at our center. The 6-year actuarial relapse-free survival (RFS) for node-negative BC after HD was 85%. Node-positive patients had a significantly lower RFS of 33% (P = .002). CONCLUSIONS: In comparison to patients with primary BC, patients who develop BC after HD are more likely to be younger, have bilateral disease, and have their tumors more frequently involve the medial half of the breast. Pathologic characteristics, nodal involvement, and prognosis are similar to those of primary BC. BC in women who were treated for HD is becoming an increasing problem, as more patients cured of HD reach a follow-up time of 10 to 15 years. Breast examination and mammography at an early age should be part of the follow-up program for women who are cured of HD.

Adolescent↗

Hepatic ganglioside abnormalities in a patient with familial erythrophagocytic lymphohistiocytosis.

Familial erythrophagocytic lymphohistiocytosis (FEL) is an autosomal recessive disease of unknown pathogenesis. Because of evidence of increased circulating and hepatic lipids in FEL, we performed a comprehensive analysis of the hepatic lipids of a patient with this disease. In contrast to normal qualitative characteristics and to normal or only mildly elevated concentrations of total lipids, neutral lipids, phospholipids, and neutral glycosphingolipids, this study reports a significant elevation of acidic glycosphingolipids, gangliosides (387 versus 147 nmole lipid-bound sialic acid/g wet weight, patient versus control). This quantitative abnormality was unusual in that it included disproportionately increased concentrations of most of the minor hepatic ganglioside species rather than either a marked increase in one single or a generalized nonspecific increase in all gangliosides, which is characteristic of known disorders exhibiting hepatic ganglioside storage. Activities of the hepatic lysosomal glycosylhydrolases which are important in ganglioside metabolism were therefore assessed by using artificial substrates. Of the enzymes tested, beta-galactosidase activity alone was remarkable, being moderately reduced (33% of that of the normal liver); no biochemical explanation for the reduction was found. The findings suggest FEL may be associated with a unique quantitative and qualitative abnormality in hepatic gangliosides, the cause of which remains to be elucidated.

Child, Preschool↗