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Biomedical subjects

W B Smith

Publications and source records attributed to W B Smith.

At least 55 records · Page 3Linked to original sources

Seborrheic keratosis with trichilemmomas masquerading as melanoma.

Seborrheic keratoses are benign lesions and, generally, are easily diagnosed based on clinical criteria. However, several types of benign as well as malignant lesions have been found associated with seborrheic keratoses, thus confusing the clinical picture. Presented is the first reported case of trichilemmomas occurring within seborrheic keratosis and masquerading as melanoma with regression. Biopsy of unusual seborrheic keratoses is recommended.

Diagnosis, Differential↗

The receptor for interleukin 3 is selectively induced in human endothelial cells by tumor necrosis factor alpha and potentiates interleukin 8 secretion and neutrophil transmigration.

Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally found in bone marrow, raising doubts as to the in vivo role of IL-3. We have found that human umbilical vein endothelial cells (HUVEC) express functional high-affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha (TNF-alpha), IL-1 beta, or lipopolysaccharide, and that this receptor is involved in inflammatory phenomena. TNF-alpha caused time- and dose-dependent up-regulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induction of mRNA correlated with protein expression on the cell surface as judged by monoclonal antibody staining and by the ability of HUVEC to specifically bind 125I-labeled IL-3. Scatchard analysis under optimal conditions of TNF-alpha stimulation revealed approximately 1500 IL-3 receptors per cell, which were of a high-affinity class (Kd = 500 pM) only. In contrast to a previous report, receptors for granulocyte-macrophage colony-stimulating factor could not be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selection expression, and neutrophil transmigration. The selective induction of a functional IL-3 receptor on endothelial cells suggests that, beyond hemopoiesis, IL-3 may have an important role in chronic inflammation and in allergic diseases.

Cell Adhesion Molecules↗

Chemotactic desensitization of neutrophils demonstrates interleukin-8 (IL-8)-dependent and IL-8-independent mechanisms of transmigration through cytokine-activated endothelium.

We have recently shown that an exogenous gradient of interleukin-8 (IL-8) induces the transendothelial migration of neutrophils. Treatment of endothelium with the cytokines IL-1 or tumour necrosis factor (TNF) also causes neutrophil transmigration, and recent evidence suggests that this may be due to endogenous IL-8 produced by the endothelium. We have used specific chemotactic desensitization of neutrophils to investigate the role of IL-8 in transmigration through cytokine-activated endothelium. Preincubation of neutrophils with IL-8 reduced their chemotactic transmigration response to an IL-8 gradient by 81%, demonstrating desensitization. Transmigration in response to cytokine-activated endothelium was inhibited by 104% after IL-8 preincubation, thus tending to support the role of IL-8. However, preincubation with another neutrophil chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP), which did not affect the IL-8, response, also inhibited transmigration, by 74%. This suggests that FMLP preincubation acts to inhibit a non-IL-8-dependent mechanism of transmigration through cytokine-activated endothelium. Chemotactic factor pretreatment of neutrophils did not reduce their adhesion to activated endothelium, but specifically blocked the transmigration step. We have therefore shown that chemotactic transmigration can be subjected to factor-specific desensitization, and have used this to provide evidence supporting a role for IL-8 in transmigration through cytokine-activated endothelium, as well as suggesting a further IL-8-independent mechanism. These data also provide a mechanism for the observed defect in accumulation of neutrophils at inflammatory sites when chemotactic factors are infused intravenously.

Cells, Cultured↗

Comparison of applanation tonometers in dogs and horses.

Two Mackay-Marg tonometers and 2 Tono-Pen tonometers were evaluated in eyes in which intraocular pressure (IOP) had been altered and measured by use of a manometer. Eyes of anesthetized dogs and enucleated horse eyes were used. Compared with the manometer, none of the tonometers accurately measured IOP over the range between 0 and 100 mm of Hg. However at manometer measurements from 0 to 30 mm of Hg, several of the tonometers accurately measured IOP. In addition, significant differences were observed when the measurement accuracy of one tonometer was compared with that of another, especially at high IOP. Coefficient of determination (r2) values for a linear model ranged from 0.979 to 0.991 in dogs, and from 0.982 to 0.996 in horse eyes.

Animals↗

Effects of prostaglandin F2 alpha and leukotriene D4 on pupil size, intraocular pressure, and blood-aqueous barrier in dogs.

In each of 5 groups of dogs, 0.05 ml of 1 of the following solutions was injected into the anterior chamber of both eyes: phosphate-buffered saline solution, 0.001 microgram of prostaglandin F2 alpha (PGF2 alpha), 0.01 microgram of PGF2 alpha, 0.1 microgram of leukotriene D4 (LTD4), and 1 microgram of LTD4. A 10% solution of sodium fluorescein was injected IV (14 mg/kg of body weight) at the same time, and pupil size, intraocular pressure, and anterior chamber fluorescence were measured for 1 hour after injections. In a dose-dependent manner, PGF2 alpha was a potent miotic. A significant effect on intraocular pressure was not detected when the groups given PGF2 alpha were compared with the control group. When compared with LTD4, PGF2 alpha significantly (P less than 0.05) increased the breakdown of the blood-aqueous barrier, as evidenced by increased fluorescein leakage into the anterior chamber. Leukotriene D4 caused a decrease in pupil size only at 5 minutes, compared with that of the control group. Intraocular pressure was greater (but not significantly) in the group given 1 microgram of LTD4.

Animals↗

Comparison of prednisolone and RMI-1068 in the ocular irritative response in dogs.

Ocular inflammation was induced in 36 dogs by performing an anterior capsulotomy with a Nd:YAG laser. All dogs were pretreated with topical atropine. Dogs were then divided into three groups: (1) control, with no other pretreatment; (2) pretreatment with the topical dual cyclooxygenase/lipoxygenase inhibitor RMI-1068; and (3) pretreatment with topical prednisolone acetate. Dogs were studied 1-3 hours after lasering. RMI-1068 maintained mydriasis and raised intraocular pressure compared to the control and prednisolone groups. An ocular fluorophotometer used to measure anterior chamber fluorescence after IV injection of sodium fluorescein showed that RMI-1068 decreased anterior chamber fluorescein concentration compared to the control and prednisolone groups. RMI-1068 decreased PGF2 alpha concentrations in the aqueous at 1 and 3 hours compared to the control and prednisolone groups. Prednisolone decreased PGF2 alpha concentrations compared to the control group at 1 h. Concentrations of LTB4 in the aqueous at 1 hour were lower in the RMI-1068 group than in the control and prednisolone groups.

Animals↗

Acute effects of anti-inflammatory drugs on neodymium:yttrium aluminum garnet laser-induced uveitis in dogs.

Dogs were treated with flunixin meglumine, a cyclooxygenase inhibitor; L-651,896, a 5-lipoxygenase inhibitor; and matrine, a herbal anti-inflammatory drug. Acute inflammation was induced in the eyes by disruption of the anterior lens capsule, using a neodymium:yttrium aluminum garnet laser. Intraocular pressure, pupil diameter, and eicosanoid production in the aqueous humor were measured. Statistically significant effects were seen in the eyes of flunixin meglumine-treated dogs where mydriasis was maintained and aqueous prostaglandin E2 concentration was reduced.

Alkaloids↗

Interleukin-8 induces neutrophil transendothelial migration.

Interleukin-8 (IL-8) is a potent neutrophil chemotactic stimulant. We have used chemically synthesized IL-8 to investigate its role in human neutrophil adhesion and transendothelial migration. IL-8 enhanced the adhesiveness of human neutrophils to plastic, and to both unstimulated and tumour necrosis factor (TNF)-stimulated endothelial monolayers in vitro. Using a two-compartment model separated by a confluent endothelial monolayer, we have shown that IL-8 chemotactic stimulation induced transmigration across the monolayer of up to 87.4 +/- 2.1% of added neutrophils (compared to random unstimulated transmigration of 2.2 +/- 0.7%), while chemokinetic stimulation led to transmigration of 21 +/- 3.8% of neutrophils. Preincubation of endothelium with TNF also induced transmigration in this model, and was additive when combined with an IL-8 chemotactic stimulus. Endothelial permeability was increased at maximal rates of chemotactic transmigration, which may correlate with increased permeability of vessels at inflammatory sites in vivo. The property of IL-8 to stimulate movement of neutrophils across endothelial monolayers in vitro supports the concept of a central role for this molecule in the accumulation of neutrophils at inflammatory lesions in vivo.

Capillary Permeability↗

The child with acute leg pain.

Diagnostic imaging is an essential component in the evaluation of a child with acute lower extremity pain or limp. Most, but not all, of the etiologies are traumatic. Frequently, the history and clinical examination are not specific. Radionuclide bone imaging is extremely rewarding in these circumstances. It represents the most useful examination used in evaluating the pathophysiology and full extent of the disorder. This article discusses the clinical presentation, pathophysiology, and characteristic imaging observations in the more common problems associated with hip and/or leg pain.

Acute Disease↗

Primary hemochromatosis in childhood.

Primary hemochromatosis is a genetic disorder rarely recognized in childhood; its long-term consequences include cirrhosis and liver cancer. We report a family with primary hemochromatosis affecting three generations, including a 7-year-old child and a 29-month-old child; these are the youngest children with primary hemochromatosis yet reported. The pathophysiology, genetics, and clinical findings of this disorder are reviewed. Serum ferritin and transferrin saturation are useful screening tests; definitive diagnosis, however, depends on determination of hepatic iron content. A plan for evaluating and treating affected patients is proposed. Physicians caring for children must learn to recognize this potentially treatable disorder.

Adult↗

Cannabis affects the severity of schizophrenic symptoms: results of a clinical survey.

Data on the history of cannabis use and a spot urine test for cannabinoids were obtained for 137 schizophrenics in treatment. Subjects who were using cannabis during the 6-month observation period presented with a significantly higher degree of delusional and hallucinatory activity than those who did not. Moreover, the group using cannabis made a higher average number of visits to the hospital during the same period. The status of cannabis use appeared to contribute to such variance more than did other relevant factors (age, stage of the illness, amount of medication prescribed, occasional use of other psychoactive substances).

Adult↗