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Biomedical subjects

J Sweet

Publications and source records attributed to J Sweet.

17 recordsLinked to original sources

Purification and characterization of Epstein-Barr virus gp340/220 produced by a bovine papillomavirus virus expression vector system.

Our initial results with a bovine papilloma virus (BPV) vector expression system indicated that we could produce significant amounts of Epstein-Barr virus (EBV) gp340/220 in the supernatant of a mouse fibroblast cell line. We have now extended these findings to show that the truncated version of gp340/220, where the membrane anchor sequence is deleted, is produced even after extended passage of the cells, at a level of approximately 1 mg/4 x 10(8) cells. A simple purification protocol using Sephacryl S300HR and gelatin agarose gives a product which is greater than 90% pure. This product is recognized by anti-gp340 monoclonal antibodies from five different epitope groups and induces antibody that recognizes the authentic gp340/220 and neutralizes EBV in vitro. The purified gp340/220 can be used in ELISA and stimulates the proliferation of T-cell clones specific for gp340/220. These characteristics, together with the fact that BPV-transformed lines have been utilized for the production of pharmaceuticals for use in humans, suggest that this gp340/220 is suitable as a source of antigen for vaccination to prevent EBV infection and related diseases.

Animals

Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen.

To evaluate the role of inflammatory mediators in the pathogenesis of the ocular allergic response, 23 subjects with positive histories of allergies to either cat dander or ragweed pollen and positive skin tests to the appropriate allergen extract were recruited and were subjected to conjunctival provocation. The tear duct of the left eye of each subject was blocked with a collagen plug while the right eye was left unplugged. In all cases, the eye was initially provoked with saline and subsequently with the appropriate allergen extract. Nonallergic subjects, or allergic subjects provoked with nonrelevant allergen, were used as control subjects. After each provocation, symptoms were recorded, and tears were collected with preweighed strips of filter paper (Schirmer strip). Each strip was placed into a tared tube containing fluid appropriate for the optimal preservation of the mediator to be measured. It was therefore possible to calculate the weight of tears collected and to express mediator levels per milliliter of tears. All allergic subjects demonstrated a positive symptomatic response to allergen challenge, whereas the control subjects remained asymptomatic. Blockage of the tear duct did not significantly alter the response. For allergic subjects, the levels of histamine, kinins, prostaglandin D2, albumin, and TAME-esterase activity were all significantly (p less than 0.005 in each case) greater after allergen challenge than after saline challenge. Furthermore, levels of each of these mediators after allergen challenge (expressed as increases above levels after saline provocation) were significantly greater for allergic subjects than for control subjects (p less than 0.005 in each case). Thus, the clinical response to conjunctival provocation with allergen is associated with increases in the levels of inflammatory mediators in tears.

Adolescent

Ancrod improves survival in murine systemic lupus erythematosus.

The effect of ancrod, a defibrinating agent, on murine lupus glomerulonephritis in the male BXSB mouse was studied to determine the relationship between macrophage procoagulant activity (PCA), fibrin deposition and glomerulonephritis. Marked renal disease and fibrin deposition were noted by three months of age in control mice, whereas little or no disease was seen in ancrod treated mice until five months of age. Similar high titers of anti-DNA antibodies and renal deposition of IgG were seen in both groups of mice. PCA rose with age in both ancrod treated and untreated mice, although it was significantly higher in control animals than in the ancrod treated group. Furthermore, ancrod therapy resulted in a decrease in plasma PCA inducing activity (PIF) and a decrease in the effectiveness of PIF to induce PCA in peritoneal macrophages in vitro. No mortality was observed in the 20 ancrod treated mice, whereas 10 of 20 control animals died. We conclude that defibrination with ancrod delays the development of renal fibrin deposition and glomerulonephritis and improves survival in BXSB mice. This was associated with a decrease in plasma PCA inducing activity and with an inhibitory effect on PCA induction. These results suggest that PCA contributes to injury in murine lupus glomerulonephritis by promoting fibrin deposition.

Ancrod

Fat embolism in acute pancreatitis.

A patient who developed progressive hypoxemia and multiple system failure during the course of acute pancreatitis is described. Autopsy showed fat emboli to the lungs, kidneys, and heart, as well as multiple petechial hemorrhages in the brain. We conclude that fat embolism should be considered in the differential diagnosis of progressive hypoxemia in patients with acute pancreatitis.

Acute Disease

Myeloma-like cast nephropathy associated with acinar cell carcinoma of the pancreas.

Obstruction of renal collecting tubules by protein cats inciting a giant cell reaction is usually characteristic of myeloma cast nephropathy. Rarely other causes of proteinuria may result in a similar morphology. We report a rare case of 'myeloma-like' tubular casts in the kidney of a patient who was subsequently found at autopsy to have acinar cell carcinoma of the pancreas with peritoneal carcinomatosis. Only two similar reports could be found in the English literature.

Carcinoma

Expression of macrophage procoagulant activity in murine systemic lupus erythematosus.

To explore the induction of monocyte/macrophage procoagulant activity in autoimmune disease, the BXSB murine model of systemic lupus erythematosus was studied. Splenic macrophage procoagulant activity rose coincident with age and the development of glomerulonephritis from 38 +/- 6 mU/10(6) macrophages at 1 mo to a maximum of 29,000 +/- 15,000 mU at 4 mo. Macrophages from 1-mo-old mice could be induced to express a 1,000-fold increase in monocyte/macrophage procoagulant activity when incubated with lymphocytes or lymphocyte supernatants from 5-mo-old mice. Plasma from 5-mo-old but not from 1-mo-old mice was able to induce the production of the lymphokine by cells from 1-mo-old animals. This lymphokine was not interleukin 1,2, or gamma interferon. We conclude that induction of monocyte/macrophage procoagulant activity parallels disease development in the male BXSB mouse, is dependent on the interaction between lymphocytes and plasma factors, and may be important in mediation of injury in lupus nephritis.

Age Factors

Focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis is an important cause of the nephrotic syndrome in children and adults. This paper reviews the pathogenesis, clinical manifestations, morphology, and treatment of focal glomerulosclerosis. In addition, it considers the recently described association of focal glomerulosclerosis with nonglomerular renal diseases and the possible role of this glomerular lesion in progressive renal failure.

Glomerulonephritis

The significance of focal segmental glomerulosclerosis in oligomeganephronia.

Oligomeganephronia (OMN) is characterized by a reduced number of nephrons, with compensatory hypertrophy of the remaining glomeruli and tubules. The clinico-pathological features of six cases seen at The Hospital for Sick Children, Toronto were reviewed. One patient presented in infancy (10 days of age), the others between 12.8 and 14.5 years (mean 13.7 years), with long-standing polydipsia and polyuria, enuresis, and growth retardation. All patients had proteinuria which tended to increase as the disease progressed. At renal biopsy, four patients showed significant proteinuria (greater than 1.3 g/24 hr). Biopsies from these patients showed focal segmental glomerulosclerosis (FSGS) and all have rapidly progressed to dialysis/transplantation. The two remaining patients had lesser degrees of proteinuria (less than 0.3 g/24 hr) and no evidence of FSGS on biopsy; however, they are currently in chronic renal failure (mean serum creatinine 2.8 mg/dl). We conclude that increasing proteinuria in patients with OMN heralds the development of FSGS, presumably due to functional overload of the reduced nephron number. This is associated with a rapid decline in renal function.

Adolescent

Circulatory, plasma catecholamine, cortisol, lipid, and psychological responses to a real-life stress (third molar extractions): effects of diazepam sedation and of inclusion of epinephrine with the local anesthetic.

We studied the circulatory, psychological, plasma catecholamine, cortisol, and lipid responses to a real-life stress--third molar extractions--in 21 patients and the effects of sedation with intravenous diazepam and of inclusion of epinephrine with the local anesthetic. Across all patients, the surgery was associated with significantly increased heart rate (25%), systolic blood pressure (13%) and cardiac output--as indicated using impedance cardiography (34%)--without a significant change in diastolic blood pressure. Plasma norepinephrine increased by 60% during the surgery in nonsedated patients. Diazepam sedation abolished the norepinephrine response to the surgery, without significantly affecting the heart rate or systolic pressure responses. Receipt of epinephrine with the local anesthetic resulted in a fivefold increase in mean plasma epinephrine 5 min after the injection, as well as increased cardiac output. The direct effect of epinephrine accounted for the cardiac output increase observed during the surgery. The results suggest the participation of the sympathetic nervous system in producing the circulatory responses to dental surgery. The elimination of sympathetic recruitment by diazepam-induced sedation, however, without concomitant reductions in heart rate or systolic pressure responses, suggests that other systems besides the sympathetic nervous system influence the circulatory response to this real-life stress.

Adolescent

Amyloidosis and systemic lupus erythematosus.

A 59 year old man with systemic lupus erythematosus developed proteinuria and renal insufficiency. Renal biopsy revealed both crescentic glomerulonephritis and amyloid in glomeruli and blood vessels. The amyloid was characterized as secondary because of its sensitivity to potassium permanganate pretreatment of Congo red stained sections. Amyloidosis is very uncommon in systemic lupus erythematosus but may be a cause of steroid unresponsive proteinuria and renal insufficiency.

Amyloidosis

Factor analysis of the Luria-Nebraska Neuropsychological Battery: IV. Intelligence and Pathognomonic Scales.

This paper examined the factor structure of the Luria-Nebraska Neuropsychological Battery Scales Intelligence and Pathognomonic. The subjects for the study were 270 patients, including 90 normal patients, 90 psychiatric patients, and 90 neurological patients. A principal factor analysis with communalities on the diagonal and iterated to the most ideal solution was used, followed by rotation to the simplest factor structure. The analysis yielded 4 subfactors for each of the two Luria scales. On the Intelligence scale, factors were general verbal intelligence, arithmetic, a frontal verbal factor, and a right frontal sequencing factor. Analysis of the Pathognomonic scale yielded a simple perceptual/expressive factor, a construction speed factor, a basic visual/spatial factor, and a higher cognitive factor. These results were generally in accord with Luria's theories.

Adult