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Biomedical subjects

W L Smith

Publications and source records attributed to W L Smith.

At least 271 records · Page 15Linked to original sources

Association of a solubilized prostaglandin E2 receptor from renal medulla with a pertussis toxin-reactive guanine nucleotide regulatory protein.

Prostaglandin E2 (PGE2) was found to bind specifically, reversibly, and in a protein-dependent manner to a single class of high affinity (KD approximately equal to 20 nM) binding sites in membranes prepared from canine renal outer medulla. PGE2 binding activity was solubilized from these membranes in a stable form (t1/2 greater than 14 days) in the absence of ligand in 75% yields using digitonin. The characteristics of PGE2 binding to membranes and solubilized protein were similar with respect to pH dependence, KD for PGE2, and order of potency of prostaglandins (PGE2 approximately PGE1 greater than PGF2 alpha greater than PGD2) in inhibiting the binding of [3H]PGE2. Importantly, the extents of binding of PGE2 to membranes and to a solubilized preparation partially purified by chromatography on wheat germ agglutinin-Affi-Gel 10 were both increased about 2-fold by GDP and GTP and its analogs. Treatment of the digitonin-solubilized PGE2 binding activity with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) rendered the binding activity insensitive to stimulation by GTP and decreased the apparent molecular weight of the peak of PGE2 binding activity from about 175,000 to about 65,000. These results suggest that the PGE2 binding activity resides in a protein which is tightly associated with, but distinct from, a guanine nucleotide regulatory (N) protein. PGE2 (greater than or equal to 10 nM) was found to stimulate GTPase activity of renal outer medullary membranes, and this stimulation was eliminated by pretreatment of membranes with pertussis toxin and NAD, but not cholera toxin and NAD. Treatment of both particulate and solubilized preparations of PGE2 binding activity with pertussis toxin plus NAD also eliminated the ability of GTP to stimulate PGE2 binding. This evidence indicates that it is the inhibitory guanine nucleotide regulatory protein, Ni, with which the PGE2 binding activity is associated. Thus, this PGE2 binding activity is an inhibitory PGE2 receptor, quite possibly one that mediates inhibition of vasopressin-induced cAMP formation in the medullary thick ascending limb and/or collecting tubule of the kidney.

Animals↗

Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility.

The antiemetic activity, gastric motor activity, and dopamine receptor effects of metoclopramide, dazopride, and sulpiride were assessed to establish if enhancement of gastric motility or antagonism of central dopamine receptors is the predominant action for drug-induced suppression of cisplatin-induced emesis. Emesis produced in dogs by cisplatin is antagonized by metoclopramide and dazopride. The antiemetic actions of metoclopramide and dazopride are associated with their ability to enhance gastric motor activity. Dazopride, unlike metoclopramide, has minimal dopamine receptor antagonist properties. Sulpiride is a potent dopamine receptor antagonist; however, it had no effect on the stomach and was ineffective in suppressing cisplatin-induced emesis.

Animals↗

Hepatic imaging in stage IV-S neuroblastoma.

Stage IV-S neuroblastoma describes a group of infants with tumor spread limited to liver, skin, or bone marrow. Such patients, who constitute about 25% of affected infants with neuroblastoma, may expect spontaneous tumor remission. We report 18 infants with Stage IV-S neuroblastoma, 83% of whom had liver involvement. Imaging investigations included Technetium 99m sulfur colloid scan, ultrasound, and CT. Two patterns of liver metastasis were noted: ill-defined nodules or diffuse tumor throughout the liver. Distinction of normal and abnormal liver with diffuse type metastasis could be quite difficult, particularly with liver scans. We conclude that patients with Stage IV-S neuroblastoma have ultrasound or CT examination as an initial workup, with nuclear medicine scans reserved for followup studies.

Adrenal Gland Neoplasms↗

Neonatal small left colon in an infant with cystic fibrosis.

A small left colon has been observed in neonates due to several causes: aganglionosis, meconium plug, and neonatal small left colon syndrome. We report a case of small left colon in an infant with cystic fibrosis, underscoring the need to consider this disease in the diagnostic work up.

Adult↗

Per anal balloon dilatation of a post-necrotizing enterocolitis stricture of the sigmoid colon.

Per anal balloon dilatation of a sigmoid colon stricture caused by necrotizing enterocolitis allowed identification of a more proximal lesion which would otherwise have gone radiographically undetected. Repeated dilatations at two weeks and four weeks following the initial dilatation of the stricture resulted in relief of the stricture and obviated the need for surgical treatment of this lesion.

Angioplasty, Balloon↗

Intravenous SRS-induced increases in tracheal mucous gel layer thickness: evidence for thromboxane involvement.

Intravenous (IV) slow reacting substance (SRS) challenge produces bronchoconstriction that can be reduced by cyclooxygenase inhibitors. This report shows that IV SRS challenge also produces significant increases in tracheal mucous gel thickness and that the increases are inhibited by pretreatment with indomethacin (4 mg/kg, PO) or imidazole (10 mg/kg, IV). The increase in gel thickness is preceded by increases in plasma thromboxane B2 (TXB2) levels and the inhibition of gel thickening by imidazole is paralleled by decreases in plasma TXB2 levels. Aerosolized SRS produces increases in tracheal mucous gel thickness which are not inhibited by either indomethacin or imidazole, but are significantly inhibited by FPL-55712. These findings indicate that SRS acts, not only directly to stimulate mucous secretion but also indirectly through an indomethacin and imidazole sensitive mechanism.

Aerosols↗

Magnetic resonance imaging of intracranial injuries from child abuse.

Magnetic resonance imaging (MRI) and computed tomography (CT) were compared in four children who had evidence of intracranial injury caused by shaking. All children had intracranial bleeding, neurologic impairment, and history or physical examination findings suggestive of child abuse. Three had bilateral retinal hemorrhages, and three had visual impairment. MRI revealed bilateral subdural hematomas in all four children, but CT showed this in only one. Skull fractures in one patient were visualized by CT alone. MRI alone demonstrated posterior fossa bleeding in one patient and intraparenchymal bleeding in another; an additional patient in whom CT showed relatively diffuse atrophy also had defined areas of focal atrophy apparent on MRI. Subarachnoid hemorrhages were equally well detected using CT or MRI. Overall, MRI was superior to CT for detection of intracranial injury caused by shaking, and may help to document milder instances of this form of child abuse.

Brain Injuries↗

A resident perspective on the radiology residency. The critical incident technique.

A recent job analysis of the radiology residency from the perspective of staff physicians revealed that radiology staff emphasized nonacademic factors such as conscientiousness, curiosity, and interpersonal skills in considering resident performance. The present study comprises a replication and extension of that work, considering the role of the resident from the perspective of the trainees. Critical incident interviews were conducted with residents at all levels in the residency (years 1 through 4). Two types of analyses were conducted, one in which residents independently developed taxonomies for these incidents, and one in which resident incidents were compared with faculty incidents in the taxonomy developed in the earlier study. Similarities to and differences from the faculty perspective were noted. Results provided support for the importance of evaluating factors other than academics in resident performance.

Attitude of Health Personnel↗

Prostaglandin biosynthesis and its compartmentation in vascular smooth muscle and endothelial cells.

PGI2 is the major, if not the only, eicosanoid formed by smooth muscle and endothelial cells of large arteries and veins. PGI2 is not the major prostanoid synthesized by microvessels. Different stimuli elicit prostanoid production by smooth muscle and endothelial cells. PGI2 is formed at several subcellular sites within smooth muscle and perhaps endothelial cells, but the consequences of this highly unusual distribution are unknown. PGI2 formed by the endothelium can exit on the luminal surface to modulate the functions of circulating blood cells, and probably on the abluminal surface to relax underlying smooth muscle. PGI2 formed by smooth muscle probably acts only upon smooth muscle cells.

Animals↗

Impact of MR imaging on clinical diagnosis and management: a prospective study.

The clinical value of magnetic resonance (MR) imaging was prospectively evaluated in 189 patients referred for examination of the brain or spine. Comparison of the attending physician's diagnosis, proposed treatment, and estimated prognosis before and after MR imaging indicated a substantial effect of the additional information provided by this study. A suspected diagnosis was refined or changed in 16% of all patients, and the physician's level of confidence in the diagnosis changed in over half of the cases in which the diagnosis was unchanged. In two-thirds of all cases the physician indicated that the treatment or estimated prognosis was altered.

Brain Diseases↗

Immunodissection and culture of rabbit cortical collecting tubule cells.

A mouse monoclonal antibody designated IgG3(rct-30) has been prepared that reacts specifically with an antigen on the surface of all cells comprising the cortical and medullary rabbit renal collecting tubule including the arcades. Plastic culture dishes coated with IgG3(rct-30) were used to isolate collecting tubule cells from collagenase dispersions of rabbit renal cortical cells by immunoadsorption. Typically, 10(6) rabbit cortical collecting tubule (RCCT) cells were obtained from 5 g of renal cortex (2 kidneys). Initial purity was greater than 96% based on immunocytofluorescent staining with three different anti-collecting tubule antibodies. Between 20 and 30% of the RCCT cells were reactive with peanut lectin suggesting that RCCT cells are a mixture of principal and intercalated cells. Approximately 10(7) RCCT cells were obtained after 4 to 5 days in primary culture. Moreover, RCCT cells continued to proliferate after passaging with a doubling time of approximately 32 h. RCCT cells passaged once and then cultured 4-5 days were found 1) to synthesize cAMP in response to arginine vasopressin (AVP), prostaglandin E2 (PGE2), isoproterenol, and parathyroid hormone, but not calcitonin, prostaglandin D2, or prostaglandin I, and 2) to release PGE2 in response to bradykinin but not arginine vasopressin or isoproterenol. Our results indicate that cultured RCCT cells retain many of the hormonal, histochemical, and morphological properties expected for a mixture of principal and intercalated rabbit cortical collecting tubule epithelia. RCCT cells should prove useful both for studying hormonal interactions in the cortical collecting tubule and as a starting population for isolating intercalated collecting tubule epithelia.

Animals↗

Antenatal diagnosis and palliative treatment of nonimmune hydrops fetalis secondary to pulmonary extralobar sequestration.

The causes of nonimmune hydrops fetalis are multiple. Despite the fact that many of the affected fetuses are otherwise free of fatal abnormalities, many die in the neonatal period from pulmonary hypoplasia. The overall perinatal mortality is as high as 80%. Extralobar pulmonary sequestration is an abnormal and nonaerated mass of extra pulmonary-located lung tissue supplied by a systemic artery, and is a rare cause of nonimmune hydrops. In the only two published reports, the hydropic fetuses died at birth. Both the first antenatal diagnosis of this disorder and the first attempt at palliative in utero therapy are reported herein. Though the fetus ultimately delivered prematurely and succumbed, treatment was associated with both subjective improvements in fetal well-being and objective reversal of the hydrops.

Adult↗