Subcutaneous nodules in a patient with polyarthritis.
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Biomedical subjects
Publications and source records attributed to J P Dowling.
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Two primary sino-nasal melanomas are presented which were characterized by their botryoid growth pattern and myxoid stroma. These polypoid tumours contained small amounts of melanin and only focal areas of epithelioid cells. An in situ component was present in both of the tumours. Malignant melanoma should be considered when confronted by a myxoid tumour (with or without melanin) in the sino-nasal region. These tumours are widely infiltrative, and there is no evidence to suggest that they will behave any differently from conventional, non-botryoid, non-myxoid sino-nasal melanomas.
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We describe a patient with multicentric reticulohistiocytosis who presented, during the second trimester of pregnancy, with symmetric polyarthritis, marked erythematous, pulsatile synovial swelling of the distal interphalangeal joints of both hands, and widespread telangiectasias. She did not have the typical skin manifestations of multicentric reticulohistiocytosis. The erythema and pulsatility of the synovial swellings of the distal interphalangeal joints resolved after delivery, but she continued to have widespread active synovitis, which did not resolve until treatment with low-dose oral methotrexate was instituted.
BACKGROUND AND PURPOSE: Systemic giant cell arteritis causing cerebellar infarction due to intracranial arteritis of the anterior inferior cerebellar artery has not been previously reported. We report this infrequent occurrence and discuss the differential diagnosis. CASE DESCRIPTION: An 85-year-old woman was admitted with a 2-week history of episodic ataxia, unilateral headaches, and vomiting. She had a history of atrial fibrillation and breast carcinoma. Her mental state was initially normal, and there were right-sided cerebellar signs. An ejection systolic murmur was heard, and peripheral pulses were palpable. A postmortem examination revealed cerebellar infarction due to giant cell arteritis of the anterior inferior cerebellar artery and basilar arteries. Systemic giant cell arteritis was also present. CONCLUSIONS: Giant cell arteritis is a systemic disorder that can infrequently involve intracranial vessels, including the basilar, vertebral, and anterior cerebellar arteries. Cerebellar infarction secondary to the arteritis may occur. The distribution and size of intracranial vessel involvement is distinct from isolated cranial angiitis.
A primary leiomyosarcoma of the thyroid was seen in a 54 yr old female. The patient had a solitary, cold nodule with no abnormalities of thyroid function tests. Histologically it was composed of characteristic interlacing fascicles of spindle cells which, electron microscopically, showed thin myofilaments with focal dense bodies. Immunohistochemistry showed a strong reaction with vimentin, smooth muscle actin and desmin. No epithelial differentiation was noted immunohistochemically or ultrastructurally. No tumor recurrence was detected 15 mths after surgery. It is postulated that the smooth muscle differentiation had arisen by metaplastic change or de-differentiation with re-differentiation of anaplastic thyroid carcinoma.
We recently reported evidence for the involvement of local cellular immune activation in the immunopathogenesis of human IgA nephropathy, particularly in cases of IgA disease featuring crescent formation. In the current study, using monoclonal antibodies, we investigated whether mononuclear cells bearing receptors for interleukin 2 (IL-2R+ MNC) were present within glomeruli or associated crescents in biopsies from patients with crescentic glomerulonephritis (greater than 60% crescents, N = 19), IgA disease with crescents (N = 9), or other types of proliferative glomerulonephritis with crescents (10 to 44%, N = 6), compared with normal control kidneys (N = 10). Biopsies were further classified into those showing active (cells, fibrin) (N = 15) or inactive (sclerosed) crescents (N = 19), to determine whether IL-2R+ MNC were particularly associated with active crescent formation. Few leucocytes were found within glomerular tufts of normal kidneys (2.4 +/- 0.7 cells/glomerular cross-section; mean +/- SEM). By contrast, in biopsies from patients with active crescentic glomerulonephritis, total intraglomerular tuft leucocytes were increased to 14.0 +/- 1.7 (P less than 0.01 vs. normal kidneys), largely due to increased numbers of intraglomerular monocytes (10.4 +/- 1.1, P less than 0.01) and T cells (3.7 +/- 0.6, P less than 0.01). Biopsies with active crescents also contained significantly increased numbers of intraglomerular tuft IL-2R+ MNC (4.0 +/- 0.7, 29% of total intraglomerular leucocytes), and there was a strong correlation between the numbers of intraglomerular IL-2R+ MNC and T cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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Explants of rabbit renal parenchyma have been grown in primary tissue culture suspended within hydrated collagen gels. Light and phase contrast microscopic analysis of the first 17 days in culture is described. Pieces of NZW rabbit renal parenchyma were suspended in collagen gels and bathed in supplemented RPMI 1640 medium and incubated at 37 degrees C in 5% CO2 in air. Tubules demonstrated a fine granularity by phase contrast microscopy and glomeruli appeared as red spheres. Blebs formed at the sides and ends of the explant and a monolayer outgrowth of tightly packed polygonal cells occurred from day 4. Histologically an immediate phase of necrosis was followed by regeneration whereby tubules became lined with a confluent epithelium composed of a single layer of flat to cuboidal-shaped cells sitting on an intact tubular basement membrane (TBM). Intraluminal casts of organized cellular debris as well as material presumed to be Tamm Horsfall protein were present. Glomeruli demonstrated collapsed capillary loops. The interstitium became widened by eosinophilic material. The tissue surface contained epithelial cells arranged in places into sac-like structures enclosing a space.
The details of a patient with disseminated scleromyxedema related to multiple myeloma are presented. Investigation demonstrated extensive accumulation of mucopolysaccharides in the skin, bone marrow and the small bowel submucosa. The latter finding is a most unusual manifestation of scleromyxedema and appeared to correlate with the patient's symptoms on presentation.
A primary tumor composed of mature adipose tissue and smooth muscle occurring in the anterior abdominal wall of a 46 yr old Filipino woman is described. The tumor was not attached to the uterus, but had an appearance similar to a uterine lipoleiomyoma. It appeared as a soft, rubbery, encapsulated 11 cm ovoid mass with a uniform, white cut surface. Histologically, there were long intersecting bundles of bland smooth muscle mixed with nests of mature fat cells. The presence of differentiated smooth muscle was confirmed by fuchsinophilia, desmin positivity and electron microscopy. The patient also had 6 intramural leiomyomas, an area of adenomyosis, a subcutaneous lipoma of the subscapular region and chronic schistosomiasis of the appendix and left adnexa.
Our previous immunohistologic studies with monoclonal antibodies (mAb) showed that glomerular and interstitial accumulations of mononuclear cells (MNC) were common features of many types of proliferative glomerulonephritis, especially crescentic glomerulonephritis. The current study examined a series of patients with crescentic IgA disease, since IgA disease in general has a highly variable course and the presence of crescents is one indicator of likely progression to end-stage renal failure. We compared the intraglomerular and interstitial infiltrates within biopsies from patients with crescentic IgA nephropathy (N = 5) versus those with noncrescentic IgA (N = 18), or normal controls (N = 10). Few leucocytes were found within glomeruli of normal (2.4 +/- 0.7 cells/glomerular cross section) (mean +/- SEM) or noncrescentic IgA disease biopsies (3.8 +/- 0.7), and no activated MNC bearing receptors for interleukin-2 (IL-2R) were detected. By contrast, in crescentic IgA disease, glomerular leucocytes were increased (5.1 +/- 0.6, P less than 0.01), due to increased monocyte (3.1 +/- 0.9, P less than 0.01) and T cell (1.4 +/- 0.4, P less than 0.01) infiltration, and IL-2R + MNC were then observed (1.2 +/- 0.5, P less than 0.05). Studies of interstitial cells showed small numbers of leucocytes within normal kidneys (101 +/- 16/mm2). Biopsies from noncrescentic IgA disease showed a fivefold increase in interstitial MNC infiltration (total leucocytes 565 +/- 105/mm2, P less than 0.01), due to an influx of T cells (283 +/- 59/mm2, P less than 0.01) and monocytes (120 +/- 32/mm2, P less than 0.01), and including a mean of 20% IL-2R+ MNC (114 +/- 29/mm2, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms for initiation of glomerular fibrin deposition were studied using renal tissue obtained from two patients with rapidly progressive, crescentic glomerulonephritis. Histological examination showed extensive glomerular monocyte infiltration and fibrin deposition in both patients. Sonicated cell suspensions of isolated glomeruli from these patients contained markedly augmented levels of procoagulant activity (PCA) compared with the levels found in normal glomeruli. This PCA was characterized as tissue factor by its functional dependence on Factors VII and V, independence of Factors VIII and XII, inhibition by concanavalin A and phospholipase C, and association with cell membranes. Its coagulant activity was also inhibited by a specific monoclonal anti-human tissue factor antibody. Tissue factor could be identified in glomeruli from these two patients by indirect immunofluorescence using this antibody. These studies implicate extrinsic pathway activation via tissue factor in intraglomerular deposition of fibrin in these patients. Activated monocytes, known to be a potent source of procoagulant activity and seen in large numbers within glomeruli from these patients, are a likely source of this tissue factor.
A monoclonal antibody, Leo Mel 3, raised against a melanoma cell line (LiBr), binds to a carbohydrate determinant of cell surface gangliosides, the simplest of which is GD3. This monoclonal antibody was screened for by its capacity to block the recognition and lysis of the melanoma cells by cytotoxic T-lymphocytes with anomalous killer cell function, illustrating a novel approach for identifying monoclonal antibody to biologically relevant tumor-associated antigens. Leo Mel 3 reacted selectively with melanoma cells by indirect immunofluorescent and immunoperoxidase staining; it reacted with tissue from all primary and metastatic melanoma tested, and it bound to cells from all but one of six cultured melanoma cell lines. Leo Mel 3 did not react with a variety of carcinomas, lymphomas, leukemias, and other neuroectodermal tumors, nor with adult or fetal tissues, except fetal liver. Very weak staining of cutaneous basal melanocytes was noted in a minority of skin sections, and 50 to 80% of melanocytes in four of seven benign nevi showed weak to moderate reactivity. The antibody was relatively specific for human adherent melanoma cells, since it did not bind to the adherent murine B16 melanoma line nor to a nonadherent human melanoma cell line (PMC-22). Expression of the Leo Mel 3-defined antigen was unrelated to changes in cell cycle. When cells from an adherent melanoma cell line were detached and maintained briefly in suspension culture, the cells became markedly less reactive with Leo Mel 3 and, after readherence to plastic, they rapidly reexpressed higher levels of the ganglioside antigen; since Leo Mel 3 prevented attachment and growth of melanoma cells in vitro, a functional role for the ganglioside is suggested in cell adhesion and metastasis. Differentiation of melanoma cells with dimethyl sulfoxide, retinoic acid, and theophylline resulted in a marked and selective increase in the amount of Leo Mel 3-defined antigen, together with an increase in the target cell binding ability of these cells, assessed by cold target competition assays using anomalous killer cells.
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This report describes a case of stable mixed connective tissue disease (MCTD) with development of acute scleroderma with hypertension, oliguric renal failure, microangiopathic hemolytic anemia, and pulmonary infiltrates. The renal histology in the acute episode was that of scleroderma with intimal sclerosis and 'onion skinning' of vessels and glomerular ischemic injury but with no evidence of damage by immune complexes either histologically or by immunofluorescence. improvement occurred after treatment with plasmapheresis, cyclophosphamide, and captopril with return of near normal renal function.
A model of glomerulonephritis induced in preimmunized rats with cationic albumin is described. Extensive glomerular immune complex formation and a severe nephrotic syndrome occurred within 5 days of commencement of daily intravenous injections. Severity of disease was markedly influenced by the degree of preimmunization and, to a lesser extent, by the dose of cationic albumin administered. Immune deposits, although initially confined along the capillary loops, were seen at all sites in the glomerulus. This study confirms that, in rats, the use of cationic antigens accelerates the development of 'serum sickness' nephropathy but preimmunization is necessary to produce significant disease.