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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 361 records · Page 20Linked to original sources

Fluorescence detection of proteases with AFC, AMC and MNA peptides using isoelectric focusing.

The fluorescence detection of proteases is not only possible with MNA but also with AFC and AMC peptides which were used up till now only for biochemical protease investigations. The MNA method is more sensitive due to the coupling capability of MNA with NSA than the AMC and AFC procedure. In comparison with the simultaneous azo-dye method the fluorescence technique may be inferior as far as the sharpness of the bands is concerned. The fluorescence staining is superior, however, if proteinases have to be investigated that are inhibited by diazonium salts, or where interference of diazonium salts and activators or inhibitors occurs; finally, it is a simple procedure to elucidate the value of MNA, AFC and AMC peptides for one and the same protease. In the field of applied isoelectric focusing the azo-dye and fluorescence procedure are now used together by us to detect possible differences in protease isoenzyme patterns in normal and diseased human biopsies, e.g. from liver, kidney and small intestine.

Animals↗

Oestrus ovis ophthalmomyiasis externa.

Oestrus ovis, the sheep nasal botfly, is the most common cause of ophthalmomyiasis externa in North America. In the United States, most cases occur on Catalina Island. The symptoms of acute infestation with this organism resemble those of catarrhal conjunctivitis and the condition is considered to be self-limiting. Treatment consists of careful removal of the organisms and topical administration of corticosteroid and antibiotic drugs to relieve the symptoms and prevent bacterial contamination. We recently examined a 17-year-old woman who had visited Catalina Island and later developed acute O. ovis ophthalmomyiasis externa. To determine the incidence of chronic complications, we performed ophthalmic examinations on 15 Catalina Island residents who had had documented O. ovis ophthalmomyiasis externa before 1981. We found no evidence of persistent infestation or intraocular penetration by these organisms.

Adolescent↗

New directions in scientific computing: impact of advances in microprocessor architecture and system design.

The new generation of microcomputers has brought computing power previously restricted to mainframe and supermini computers within the reach of individual scientific laboratories. Microcomputers can now provide computing speeds rivaling mainframes and computational accuracies exceeding those available in most computer centers. Inexpensive memory makes possible the transfer to microcomputers of software packages developed for mainframes and tested by years of experience. Combinations of high level languages and assembler subroutines permit the efficient design of specialized applications programs. Microprocessor architecture is approaching that of superminis, with coprocessors providing major contributions to computing power. The combined result of these developments is a major and perhaps revolutionary increase in the computing power now available to scientists.

Computers↗

A solid-state instrument for measuring dynamic changes in the pupil of the human eye.

An instrument for making dynamic measurements of the human pupil is described. The device uses a 100-element linear self-scanning photodiode array and a Z80A microprocessor system. The eye is imaged using infrared radiation. The instrument has both analogue and digital outputs of pupil diameter, which are accurate to better than +/- 2.5% of full scale. By compensating for the inherent nonuniformities in the photodiode array, the microcomputer maintains the accuracy and reliability of the system at low irradiance levels. A simple means of implementing a two-dimensional measuring system is proposed.

Biomedical Engineering↗

Pathogenesis of osteopetrosis induced by rapid and slow onset plaque isolates of an avian osteopetrosis virus.

Examination of bone from chickens infected as 10-day-old embryos with isolates of an avian osteopetrosis virus revealed that MAV-2(O) plaque isolate 32/2/4 caused rapid bone growth, while MAV-2(O) plaque isolate 13 caused a mild form of bone growth. MAV-2(O) plaque isolate 32/2/4 caused anemia when injected into the 8-day-old hatched chick and bone growth in ovo when injected into the 4-day-old embryo. Passive administration of neutralizing antibody protected against MAV-2(O)-induced bone growth when antibody was given to the embryo 1 day after virus. Neutralizing antibody also protected against an acute anemia observed when normal and bursectomized chickens were given MAV-2(O) 32/2/4, but antibody did not prevent the appearance of a chronic anemia or osteopetrosis in bursectomized chickens. Repeated animal passage of a slow onset plaque isolate of MAV-2(O) caused the virus to progressively induce more severe bone growth and anemia.

Anemia↗

Variable clinical response to choline in tardive dyskinesia.

Tardive dyskinesia is widely believed to be a state of relative hyperdopaminergic and hypocholinergic imbalance in the striatum of patients chronically treated with neuroleptics. However, not all patients with tardive dyskinesia respond to cholinergic drugs, which theoretically should restore the balance and improve the symptoms. We report a controlled, double-blind, crossover study of choline chloride in 11 patients with persistent tardive dyskinesia. Seven patients showed partial or minimal improvement, while two did not change and two deteriorated. The results are discussed in the light of other similar findings in the literature, and the implications for pharmacological subtypes of tardive dyskinesia using cholinergic probes are explored.

Acetylcholine↗

Ketamine kinetics in unmedicated and diazepam-premedicated subjects.

Plasma ketamine concentrations after diazepam and placebo pretreatment were examined in a double-blind, randomized, cross-over study. Eight healthy male subjects received either diazepam or a 0.9% NaCl placebo before ketamine and received the alternate combination 5 to 24 days later. Ten minutes before ketamine dosing, diazepam, 0.3 mg/kg, or placebo in equal volume was injected intravenously at a rate not exceeding 5 mg/min. Ketamine, 2.2 mg/kg iv, was injected over 1 min. For the clinically relevant period for anesthesia (1 to 30 min), diazepam-ketamine treatment resulted in higher plasma levels at most time points, but diazepam pretreatment did not alter plasma levels of metabolite KI and pseudometabolite KII nor the 24-hr urinary excretion of ketamine, KI, and KII. Ketamine kinetics followed a three-term exponential decline under both treatment conditions. After placebo-ketamine dosing, plasma t 1/2s were as follows: distribution (pi t 1/2) = 24.1 sec, redistribution (alpha t 1/2) = 4.68 min, and elimination (beta t 1/2) = 2.17 hr. After diazepam-ketamine dosing, t 1/2s were: pi t 1/2 = 25.0 sec, alpha t 1/2 6.37 min, and beta t 1/2 = 2.32 hr.

Adult↗

Theophylline precipitated alterations of lithium clearance.

The effect of steady state therapeutic theophylline serum levels on lithium clearance was investigated. A significant increase in lithium clearance occurred with the administration of theophylline. Despite considerable intersubject variability, a direct lithium clearance estimation method demonstrated a mean increase of 30% with the addition of theophylline. The concomitant use of lithium and theophylline potentially may alter lithium levels sufficiently to result in manic or depressive relapses in patients receiving lithium prophylactically.

Adult↗

Specificity of avian leukosis virus-induced hyperlipidemia.

Rous-associated virus 7 (RAV-7) is a subgroup C avian leukosis virus which does not transform cells in vitro or carry an oncogene. When injected into 1-day-old hatched chicks, RAV-7 causes a low incidence of lymphoid leukosis after a latent period of several months. In contrast, infection of 10-day-old chicken embryos with RAV-7 leads to a disease syndrome characterized by stunting, obesity, atrophy of the bursa and the thymus, high triglyceride and cholesterol levels, reduced thyroxine levels, and increased insulin levels (Carter et al., Infect. Immun. 39:410-422, 1983; J.K. Carter and R.E. Smith, Infect. Immun. 40:795-805, 1983). Histopathological examination of tissues from affected chicks revealed an accumulation of lipid in the liver and an extensive infiltration of the thyroid and pancreas by lymphoblastoid cells. In the present investigation, the subgroup specificity of this syndrome was investigated. Other subgroup C avian leukosis viruses (transformation-defective B77, transformation-defective Prague C strain of Rous sarcoma virus, and RAV-49) caused stunting, infiltration of the thyroid and pancreas, increased liver weights, decreased thyroxine levels, and increased insulin levels, but they did not cause a uniform, profound increase in triglyceride and cholesterol levels. Avian leukosis viruses of subgroup A [myeloblastosis-associated virus 1 causing osteopetrosis [MAV-1(O)] and RAV-1], subgroup B [MAV-2(O), MAV-2 causing nephroblastoma [MAV-2(N)], and RAV-2], subgroup D (RAV-50), and subgroup F (ring-necked pheasant virus and RAV-61) did not cause a syndrome identical to that induced by RAV-7. All of the viruses examined induced some stunting and a reduction in thyroxine levels which correlated with the stunting. The two subgroup F viruses caused an infiltration of the thyroid which may have been secondary to severe lung involvement. We conclude that the RAV-7 syndrome is unique, particularly in the induction of a hyperlipidemia.

Animals↗

Mechanisms of oncogenesis by subgroup F avian leukosis viruses.

Subgroup F avian leukosis viruses, such as RAV-61 and ring-necked pheasant virus, are recombinants between exogenous chicken retroviruses and endogenous pheasant viruses and contain new envelope (env) genes. Chickens infected as 10-day-old embryos with subgroup F viruses develop fibrosarcomas, nephroblastomas, osteopetrosis, B-cell lymphomas, and a high incidence of a proliferative disorder involving the lung. Fibrosarcomas, nephroblastomas, and lymphomas appear after long latent periods (3 to 12 months). They contain discrete virus-cell junction fragments and are therefore clonal outgrowths of a single infected cell. Two ring-necked pheasant virus-induced B-cell lymphomas and an adenocarcinoma of the abdomen contained proviruses integrated at the c-myc locus and elevated levels of myc mRNA. At least four of the fibrosarcomas appeared to contain proviruses integrated at a common site, suggesting that a specific cellular gene may be involved in these tumors. The host gene has not been identified, however; 16 different oncogene probes failed to hybridize to fibrosarcoma junction fragments. In contrast to these neoplasms, lung lesions appeared rapidly (4 to 5 weeks), showed no evidence of clonality, and lacked long terminal repeat-initiated transcripts other than viral 35S and 21S mRNA. We conclude, therefore, that subgroup F retroviruses induce the proliferative disorder of the lung by a different mechanism.

Animals↗

Identification of protease isozymes after analytical isoelectric focusing using fluorogenic substrates impregnated into cellulose membranes.

A technique to characterize active isozymes of proteases is described. After isoelectric focusing in an ultrathin gel, a cellulose diacetate or hydrate membrane previously impregnated with media containing a fluorogenic substrate is applied to the surface of the gel. Low-molecular-weight peptide inhibitors can also be added to the membrane to enhance specificity. The technique shows excellent reproducibility, specificity, and sensitivity, and has promise for the study of isozymes of proteases in tissues and body fluids in normal and pathological states.

Animals↗

The California Automated Mortality Linkage System (CAMLIS).

The California Automated Mortality Linkage System (CAMLIS), established in 1981 to facilitate the conduct of follow-up studies in the State of California, employs a combination of deterministic and probabilistic linkage decision criteria to perform the death clearance function. The system was evaluated against four traditional death clearance procedures and the performance of each procedure measured in terms of measures of sensitivity and specificity. Only one procedure was associated with a specificity lower than 0.99; for that one, the specificity was 0.93. There was much greater fluctuation in the observed sensitivity levels. In one of the procedures, CAMLIS demonstrated a sensitivity of 0.97 versus 0.79 for the Social Security Administration. A comparison against the National Death Index (NDI) produced sensitivities of 0.89 for CAMLIS and 0.94 for the NDI. An assessment of manual search procedures using a file of Japanese names produced a CAMLIS sensitivity measure of 0.92 compared with 0.93 for the manual search. Another manual search procedure using microfiche copies of the state death index produced a CAMLIS sensitivity of 0.97; in this evaluation, the sensitivity of the manual search was defined as 1.0. Another measure of performance of a death clearance procedure is its predictive value in identifying a person who has died; CAMLIS generated predictive values in these evaluations that ranged from 0.93 through 0.99, contrasted with the NDI value of 0.59.

California↗

Effect of monensin on secretion of basement membrane collagen by cultured rabbit corneal endothelial cells in comparison with rabbit tendon fibroblasts.

Monensin, a monovalent ionophore, affects differently the secretion of basement membrane collagen and interstitial procollagen. At 1 X 10(-8) M, monensin inhibited only slightly the secretion of procollagen synthesized by tendon cells while secretion of basement membrane collagen synthesized by endothelial cells was inhibited by 43% after 2 hours of labelling. At higher concentration (1 X 10(-6) M), the secretion of type I procollagen by tendon cells was inhibited after two h (36%) or 24 h (24%) of labelling. The pattern of basement membrane collagen secretion varied from inhibition to stimulation depending on the labeling time. No changes in the phenotypic expression of collagen were observed in either the monensin-treated tendon cultures or endothelial cells. Phase-contrast microscopy revealed differential responses of cells to monensin: tendon cells appeared spindle-shaped or rounded-up, in contrast to the enlarged shape displayed by endothelial cells.

Animals↗

Patient selection and survival after peritoneovenous shunting for nonmalignant ascites.

Patient selection and survival after peritoneovenous shunting for nonmalignant ascites was assessed in 30 patients undergoing 44 peritoneovenous shunting procedures over a 5-year period. Indications for peritoneovenous shunting included refractory ascites alone, refractory ascites complicated by hepatorenal syndrome, and nonrefractory but recurrent ascites. Fifty-six percent of shunting procedures were complicated by shunt malfunction and an additional 13% ended in shunt removal or ligation. Serious perioperative morbidity occurred in 47% of patients. Mean duration of shunt function was significantly less (p less than 0.05) in the patients with hepatorenal syndrome (15 +/- 5 days) compared to the patients with refractory ascites alone (45 +/- 13 days), or the patients with nonrefractory ascites (64 +/- 34 days). Mean survival was 265 +/- 87 days. Survival of patients with nonrefractory ascites (767 +/- 214 days) was significantly longer (p less than 0.05) than that seen in patients with hepatorenal syndrome (28 +/- 5 days) or in patients with refractory ascites alone (256 +/- 148 days). Combined inhospital mortality was 30%. It was significantly greater (p less than 0.05) in patients with hepatorenal syndrome (70%) than in patients with refractory ascites alone (14%) or in patients with nonrefractory ascites (0%). We conclude that patient selection significantly influences survival after peritoneovenous shunting and may account for the varying results reported by other groups.

Adult↗