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Biomedical subjects

W L Smith

Publications and source records attributed to W L Smith.

At least 289 records · Page 16Linked to original sources

Immunodissection: use of monoclonal antibodies to isolate specific types of renal cells.

Several laboratories have described antibodies that are directed against cell surface antigens unique to different renal cell types. It can reasonably be assumed that each different type of renal cell possesses one or more unique antigenic determinants. In principle, it should be possible to prepare monoclonal antibodies against these cell-specific antigens and to use the antibodies as immunoaffinity reagents to isolate populations of specific renal cell types. We employed this approach in one instance to isolate canine cortical collecting tubule (CCT) cells. Approximately 10(7) canine CCT cells can be obtained from 5 g of canine renal cortex. This compares with an estimate of 10(3) to 10(4) CCT cells that can be reasonably obtained by microdissection. The availability of relatively large numbers of cells makes it possible to study in greater detail the cellular physiology and biochemistry of tubule-specific processes such as solute and water transport and hormone action. Our experiences in attempting to isolate canine CCT cells and other renal epithelia have indicated that the ideal monoclonal antibody for immunodissection should 1) interact with only one type of renal cell, 2) be directed against a determinant present in relative abundance, 3) be noncytotoxic, and 4) be an immunoglobulin G. Described in this review are some conceptual and practical aspects of the methods that can be used to develop B lymphocyte-myeloma hybrids producing such ideal monoclonal antibodies and to isolate renal cells using cell-specific monoclonal antibodies.

Animals↗

Measurement and prediction of diagnostic performance during radiology training.

Faculty evaluations of residents' diagnostic performance in radiology subspecialty rotations were examined in two studies in order to ascertain whether the relative capabilities of residents change during training and to predict residents' diagnostic performance using a three-dimensional form perception test. In the first study, numeric ratings by faculty members were averaged to provide interpretive/diagnostic scores for each of 16 residents in each of 5 consecutive half-years. Sixty-seven percent of the relative differences among residents' diagnostic proficiencies persisted during training. The magnitude of these unchanging differences between individuals in diagnostic performance strongly favors resident selection based upon diagnostic potential. An additional 22% of the relative differences correlated with an abrupt change in the rank order of residents in diagnostic performance at the beginning of the second year of residency. This rearrangement of ranks may have resulted from an abrupt change in the tasks and expectations assigned to residents. In the second study, correlations between scores on a recently described Form Test and monthly faculty ratings of diagnostic performance were computed. An average diagnostic performance score for each resident was generated for all rotations combined, each of eleven subspecialties, and all rotations completed within a given half-year. Scores on the Form Test correlated well with these combined diagnostic scores, further substantiating results reported previously. Form Test scores were highly correlated with subspecialty diagnostic performance scores in subspecialties using cross-sectional imaging methods, such as neuroradiology. Although Form Test scores were poorly correlated with half-year diagnostic performance during the first year, they were highly correlated with performance beginning in the second year.

Educational Measurement↗

Head ultrasound screening in premature neonates weighing more than 1,500 g at birth.

During a 14-month period, 112 consecutively born neonates with a birth weight between 1,501 and 2,000 g were screened by cranial ultrasonography. Nineteen patients (17%) had abnormal scans. Of these abnormalities, 14 (13%) were germinal matrix hemorrhage and/or intraventricular hemorrhage. Although the incidence of hemorrhage in these larger premature neonates is less than that which has been described in neonates with a birth weight less than 1,500 g, the severity of the hemorrhage, mortality (21%), morbidity, and outcome were similar to those seen in smaller neonates. More than half of the hemorrhages identified were severe, ie, grades III and IV. The clinical picture in these neonates was striking in that each suffered severe birth asphyxia and/or required ventilation shortly after birth. Therefore, screening all larger premature neonates is probably not warranted and selective screening will be adequate to identify those neonates who need intervention or would benefit from developmental follow-up.

Asphyxia Neonatorum↗

Intraluminal meconium calcification without distal obstruction.

Intraluminal meconium calcification of unknown mechanism is reported in three neonates who did not have distal intestinal obstruction. The condition was benign in all three cases and did not require surgical intervention. This new form of intra-abdominal calcification should be differentiated from other forms that invariably are due to surgical disorders.

Calcinosis↗

Neonatal intracerebellar hemorrhage: detection by real-time ultrasound.

Two cases of primary intracerebellar hemorrhage in premature neonates in which diagnosis was established primarily by real-time ultrasound are presented. It is concluded that real-time, portable ultrasound should be the diagnostic method of choice in evaluating the brain in infants on multiple life-support systems.

Cerebellar Diseases↗

Critical incident interviewing in evaluation of resident performance.

To identify evaluation procedures for selection of radiology residents, this study was performed to describe the criteria that indicate successful resident performance. The critical incident technique, a method previously used in industrial settings, was applied. Structured interviews with 22 senior radiology staff members produced descriptions of resident behavior that fell into the following six categories: knowledge, technical skills and abilities, attitudes toward self, interpersonal skills, conscientiousness, and curiosity. The majority of behavioral factors appraised were in the last four categories, which describe personality variables and social skills. The results have implications for the evaluation and selection of residents.

Behavior↗

A method for measuring changes in tracheal mucus gel layer thickness as an indication of an immediate hypersensitivity response.

A visual method for measuring increase in tracheal mucus gel layer thickness as an indication of an immediate hypersensitivity response, using a Zeiss slitlamp and pachymeter is described. Mucus gel layer thickening is antigen dose dependent. Antigen challenge of nonsensitized rats does not cause significant increases in gel thickness dispelling the notion that changes in the gel layer result from nonspecific irritation. Cromolyn sodium, cimetidine, and FPL-55712 inhibit increases in gel layer thickness following antigen challenge of actively sensitized rats, while atropine, pyrilamine, and methysergide do not.

Acetylcysteine↗

Apical-basolateral membrane asymmetry in canine cortical collecting tubule cells. Bradykinin, arginine vasopressin, prostaglandin E2 interrelationships.

The studies reported here were designed to determine if there is an apical-basolateral asymmetry to the release of prostaglandins by or to the biochemical effects of prostaglandins on the renal collecting tubule. Canine cortical collecting tubule (CCCT) cells were isolated by immunodissection and seeded at supraconfluent densities on Millipore filters. The resulting confluent monolayer of CCCT cells: (a) developed and maintained a transcellular potential difference of 1 mV (apical side negative); (b) exhibited a permeability to inulin that was the same as that obtained with similar monolayers of Madin-Darby canine kidney (MDCK) cells; and (c) released adenosine 3',5'-cyclicmonophosphate (cAMP) in response to arginine vasopressin (AVP) added to the basolateral but not the apical surface of the monolayer. These results indicate that confluent monolayers of CCCT cells on Millipore filters have characteristics of asymmetry that are seen with intact collecting tubules. Moreover, PGE2 added to either side of the CCCT cell monolayer crossed the monolayer at the same slow rate as inulin, which demonstrated the feasibility of examining the sidedness of the effects of and the release of PGE2. Although AVP caused cAMP release only when added to the basolateral side of CCCT cells, AVP caused the release of PGE2 when added to either the apical or basolateral surface. This result implies that there are at least two AVP receptor systems, one coupled to cAMP synthesis and one to PGE2 formation. In contrast to the results observed with AVP, bradykinin caused PGE2 release only when added to the apical surface of CCCT cells, which suggested that urinary but not blood borne kinins elicit PGE2 formation by the canine collecting tubule. PGE2 was released in comparable amounts on each side of the monolayer in response both to AVP and to bradykinin. High concentrations (greater than or equal to 10(-8) M) of PGE2 added to either side of the monolayer caused the release of cAMP. However, at concentrations (10(-10) - 10(-12) M) at which PGE2 had no independent effect on cAMP release, PGE2 inhibited the release of cAMP, which normally occurred in response to AVP. This inhibition occurred with PGE2 added to either the apical or basolateral surface of the CCCT cell monolayer. PGE2 (10(-11) M) also inhibited the AVP-induced accumulation of intracellular cAMP by CCCT cells seeded on culture dishes. This inhibition was only observed when the cells were preincubated with PGE2 for greater than or equal to 20 min. Our results are consistent with the concept that inhibiton by prostaglandins of the hydroosmotic effect of AVP is due to inhibition of AVP-induced cAMP production. This inhibition does not appear to involve a direct physical interaction of PGE2 with the AVP receptor which is coupled to adenylate cyclase, since CCCT cells must be preincubated with PGE2 for 20 min for the inhibition to be observed, and since PGE2 added to the apical surface of CCCT cells inhibits cAMP release in response to AVP acting from the basolateral surface.

Animals↗

An evaluation of computer-assisted instruction in radiology.

The effectiveness of computer-assisted instruction in two radiologic topics was investigated. A group of fourth-year medical students received computer-assisted instruction while a control group received the same material by way of a conventional lecture. Each group was tested before and after instruction, and the group mean scores were compared. Student attitudes were elicited by questionnaire. Computer-assisted instruction was as effective as the lecture in improving the students' test performance. Subjectively, computer-assisted instruction was rated superior by the students because of its interactive nature. Applications of computer-assisted instruction in radiology education are discussed.

Computer-Assisted Instruction↗

Immunochemical evidence for the involvement of prostaglandin H synthase in hydroperoxide-dependent oxidations by ram seminal vesicle microsomes.

Monoclonal antibodies against prostaglandin H (PGH) synthase have been used to precipitate cyclooxygenase and peroxidase activities from detergent-solubilized preparations of ram seminal vesicle microsomes. Approximately 85% of the solubilized cyclooxygenase activity was precipitated using an excess of anti-PGH synthase antibody; under similar conditions, immunoprecipitation of 60% of the diphenylisobenzofuran peroxidase, 75% of the phenylbutazone peroxidase, and 50% of the epinephrine peroxidase activities occurred. In contrast, less than 10% of the cyclooxygenase or peroxidase activities could be precipitated with nonimmune, control antibody preparations. These data indicate that the hydroperoxidase activity of PGH synthase is the major peroxidase activity catalyzing the co-oxidation of xenobiotics in ram seminal vesicle microsomes.

Animals↗

Bimodal distribution of the prostaglandin I2 synthase antigen in smooth muscle cells.

Vascular and nonvascular smooth muscles in 12 different organs from the gastrointestinal, respiratory, and urogenital tracts of the rabbit, cow, dog, sheep, pig, and rat were examined for prostaglandin I2 (PGI2) synthase immunoreactivity by indirect immunocytofluorescence using monoclonal antibodies against the enzyme. Each of 35 different smooth muscle layers tested stained for the PGI2 synthase antigen except the circular smooth muscle of the rabbit large intestine. Interestingly, PGI2 synthase-positive fluorescent staining of smooth muscle was always observed to be associated with both the nuclear and plasma membranes. Our results indicate that most smooth muscle, both vascular and nonvascular, has the capacity to synthesize PGI2. Moreover, the fact that the PGI2 synthase antigen is associated with at least two different organelles in each cell suggests that there are two independent PGI2-synthesizing systems in smooth muscle; one on the nuclear membrane, and one on the plasma membrane. PGI2 formed at these different sites may subserve different functions within the same cell.

Animals↗

The use of glucagon in hydrostatic reduction of intussusception: a double-blind study of 30 patients.

Thirty patients were referred for hydrostatic reduction of ileocolic intussusception. Children with suspected gangrenous bowel or sensitivity to glucagon were excluded from the investigation. A standard protocol for the procedure was used in all patients, including the intravenous administration of glucagon or placebo (0.05 mg/kg) when the intussusception was encountered. Successful reduction was achieved in 53% of both control and glucagon-treated patients. Analysis of the length of the procedure and the ease of reduction of the intussusception indicated no difference in the two groups. This multicenter double-blind study failed to show any therapeutic value of glucagon in hydrostatic reduction of intussusception.

Barium Sulfate↗