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Biomedical subjects

A H Robbins

Publications and source records attributed to A H Robbins.

At least 19 recordsLinked to original sources

Prevention of the spread of rabies to wildlife by oral vaccination of raccoons in Massachusetts.

OBJECTIVE: To evaluate the use of bait containing rabies vaccine to create a barrier of rabies-vaccinated raccoons in Massachusetts and to determine the effectiveness of various bait distribution strategies in halting the spread of rabies. DESIGN: Prospective study. SAMPLE POPULATION: Free-ranging raccoons. PROCEDURE: Baits were distributed twice yearly in a 207-km2 (80-mi2) area in the vicinity of the Cape Cod Canal. Bait density and distribution strategy varied among 3 treatment areas. Raccoons were caught in live traps after bait distribution and anesthetized; blood samples were obtained to measure serum antibody titers to rabies virus. Vaccination rates were determined by the percentage of captured raccoons with antibody titers to rabies virus > or = 1:5. In addition, raccoons with clinical signs of illness inside the vaccination zone and adjacent areas were euthanatized and submitted for rabies testing. RESULTS: The percentage of vaccinated raccoons differed significantly among the following 3 areas with various bait densities: high-density area with uniform bait distribution (103 baits/km2 [267 baits/mi2]) = 37%; low-density area with additional targeted bait distribution (93 baits/km2 [240 baits/mi2]) = 67%; and, high-density area with additional targeted bait distribution (135 baits/km2 [350 baits/mi2]) = 77%. Nineteen animals with rabies (15 raccoons, 3 skunks, 1 cat) were reported in the area just outside of the vaccination zone, but only 1 raccoon with rabies was reported from inside the vaccination zone. CLINICAL IMPLICATIONS: In this suburban study area, an approximate vaccination rate of 63% was sufficient to halt the spread of rabies in free-ranging raccoons. Compared with uniform bait distribution, targeting raccoon habitats increased vaccination rates.

Administration, Oral↗

Human contact with bait containing vaccine for control of rabies in wildlife.

OBJECTIVE: To document the number of human contacts with bait containing liquid vaccinia-rabies glycoprotein (V-RG) vaccine, to evaluate factors that might affect human contact with bait-vaccine units, and to summarize adverse reactions in people after contact with vaccine. DESIGN: Retrospective 4-year survey of directors of 6 oral rabies vaccination programs. SAMPLE POPULATION: Human residents in areas of vaccination programs. PROCEDURE: Data were collected from report forms and telephone conversations with directors of oral rabies vaccination programs in Florida, Massachusetts, New Jersey, Texas, and New York. Data collected included information regarding human contact with bait and vaccine, sex and age of person involved in contact, human population density, bait density, type of labeling used on bait, and other factors. RESULTS: Human contact with bait was more likely in areas where bait had white labels (vs lettering in black ink) and in areas with high human population densities. Directors of all programs reported that human contact with bait-vaccine units was minimal. Adverse reactions in exposed people were not reported. On the basis of these findings, concerns about V-RG vaccine posing a substantial public health risk remain unfounded. CLINICAL IMPLICATIONS: Directors of oral rabies vaccination programs should systematically collect information about exposures and potential factors affecting exposure of people to bait-vaccine units. People with substantial exposure to V-RG vaccine should be evaluated for immune status and any resulting symptoms should be documented and monitored.

Animals↗

Teleradiology for remote diagnosis: a prospective multi-year evaluation.

Teleradiology has been used for nearly 3 years at our institution to provide urgent radiologic interpretations for two outpatient clinics and an affiliated hospital. The purpose of this study was to evaluate the clinical reliability of the existing system. Teleradiology images were interpreted using 1600 x 1200 pixel display stations. The original films from the same cases were subsequently interpreted, usually by another radiologist. The initial and final interpretations were compared. Discrepancies were rated and adjudicated by another senior radiologist. These data were compared to peer review interobserver discrepancy rates. Among the 2688 teleradiology examinations evaluated, there were major discrepancies in 31 (1.5%). In three instances teleradiology rather than film interpretation was considered correct. Abnormalities missed on teleradiology were apparent in all but two at adjudication. Among the 628 peer-review cases, there were 6 (0.96%) major discrepancies. Major teleradiology discrepancy rates are statistically similar to film-based peer review discrepancy rates. Teleradiology is suitable for providing radiologic services to remote medical facilities.

Evaluation Studies as Topic↗

Crystal structure of thioltransferase at 2.2 A resolution.

We report here the first three-dimensional structure of a mammalian thioltransferase as determined by single crystal X-ray crystallography at 2.2 A resolution. The protein is known for its thiol-redox properties and dehydroascorbate reductase activity. Recombinant pig liver thioltransferase expressed in Escherichia coli was crystallized in its oxidized form by vapor diffusion technique. The structure was determined by multiple isomorphous replacement method using four heavy-atom derivatives. The protein folds into an alpha/beta structure with a four-stranded mixed beta-sheet in the core, flanked on either side by helices. The fold is similar to that found in other thiol-redox proteins, viz. E. coli thioredoxin and bacteriophage T4 glutaredoxin, and thus seems to be conserved in these functionally related proteins. The active site disulfide (Cys 22-Cys 25) is located on a protrusion on the molecular surface. Cys 22, which is known to have an abnormally low pKa of 3.8, is accessible from the exterior of the molecule. Pro 70, which is in close proximity to the disulfide bridge, assumes a conserved cis-peptide configuration. Mutational data available on the protein are in agreement with the three-dimensional structure.

Animals↗

Comparison of the NMR solution structure and the x-ray crystal structure of rat metallothionein-2.

Metallothioneins are small cysteine-rich proteins capable of binding heavy metal ions such as Zn2+ and Cd2+. They are ubiquitous tissue components in higher organisms, which tentatively have been attributed both unspecific protective functions against toxic metal ions and highly specific roles in fundamental zinc-regulated cellular processes. In this paper a detailed comparison of the NMR solution structure [Schultze, P., Wörgötter, E., Braun, W., Wagner, G., Vasák, M., Kägi, J. H. R. & Wüthrich, K. (1988) J. Mol. Biol. 203, 251-268] and a recent x-ray crystal structure [Robbins, A. H., McRee, D. E., Williamson, M., Collett, S. A., Xoung, N. H., Furey, W. F., Wang, B. C. & Stout, C. D. (1991) J. Mol. Biol. 221, 1269-1293] of rat metallothionein-2 shows that the metallothionein structures in crystals and in solution have identical molecular architectures. The structures obtained with both techniques now present a reliable basis for discussions on structure-function correlations in this class of metalloproteins.

Amino Acid Sequence↗

Preliminary X-ray crystallographic analysis of intercellular adhesion molecule-1.

Crystals of the two amino-terminal domains of intercellular adhesion molecule-1, the receptor for the major group of human rhinovirus serotypes, diffract to 3.0 A resolution. The crystals are trigonal in space group P3(1)21 or P3(2)21 with cell dimensions of a = b = 55.7 A, c = 166.3 A, with probably six molecules per unit cell.

Antigens, CD↗

Refined crystal structure of Cd, Zn metallothionein at 2.0 A resolution.

The crystal structure of Cd5,Zn2-metallothionein from rat liver has been refined at 2.0 A resolution of a R-value of 0.176 for all observed data. The five Cd positions in the asymmetric unit of the crystal create a pseudo-centrosymmetric constellation about a crystallographic 2-fold axis. Consequently, the distribution of anomalous differences is almost ideally centrosymmetric. Therefore, the previously reported metal positions and the protein model derived therefrom are incorrect. Direct methods were applied to the protein amplitudes to locate the Cd positions. The new positions were used to calculate a new electron density map based on the Cd anomalous scattering and partial structure to model the metal clusters and the protein. Phases calculated from this model predict the positions of three sites in a (NH4)2WS4 derivative. Single isomorphous replacement phases calculated with these tungsten sites confirm the positions of the Cd sites from the new direct methods calculations. The refined metallothionein structure has a root-mean-square deviation of 0.016 A from ideality of bonds and normal stereochemistry of phi, phi and chi torsion angles. The metallothionein crystal structure is in agreement with the structures for the alpha and beta domains in solution derived by nuclear magnetic resonance methods. The overall chain folds and all metal to cysteine bonds are the same in the two structure determinations. The handedness of a short helix in the alpha-domain (residues 41 to 45) is the same in both structures. The crystal structure provides information concerning the metal cluster geometry and cysteine solvent accessibility and side-chain stereochemistry. Short cysteine peptide sequences repeated in the structure adopt restricted conformations which favor the formation of amide to sulfur hydrogen bonds. The crystal packing reveals intimate association of molecules about the diagonal 2-fold axes and trapped ions of crystallization (modeled as phosphate and sodium). Variation in the chemical and structural environments of the metal sites is in accord with data for metal exchange reactions in metallothioneins.

Amino Acid Sequence↗

Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease.

Data from various laboratories have indicated associations of various alleles determined by RFLPs within or adjacent to several apolipoprotein genes with abnormalities in plasma lipids and/or premature coronary artery disease (CAD). In order to assess such relationships we have examined allele frequencies of 8 different RFLPs within or adjacent to the apo A-I, C-III and A-IV gene complex on the long arm of chromosome 11 (MspI, 5' to the apo A-I gene; MspI, within the apo A-I gene; PstI, 3' to the apo A-I gene; SstI, 3' to the apo C-III gene; PvuII, within the apo C-III gene; PvuII, 5' to the apo C-III gene; XbaI, within the apo A-IV gene; and XbaI, 3' to the apo A-IV gene) in 202 patients with CAD (50% narrowing of one or more coronary arteries) prior to age 60 and 145 normal controls. None of the allele frequencies of these RFLPs were significantly different in cases as compared to controls. With regard to associations with plasma lipids and apolipoprotein levels, the rare allele determined by the absence of the PstI site was associated with elevated triglyceride levels (P less than 0.05) in cases, but not in controls. In contrast, the rate MspI allele 5' to the apo A-I gene was associated with elevated triglyceride levels (P less than 0.05) in controls but not in cases. In both cases and controls, subjects with the uncommon SstI allele had triglyceride levels that were 9 and 38% higher than in those without this allele. These differences were significant (P less than 0.05) only in controls. Our data indicate that the rare allele determined by the SstI site within this gene complex deserves further study in order to understand its association with elevated triglycerides in Caucasian populations. However, at the present time all these DNA markers lack sufficient specificity to be clinically useful for CAD risk assessment.

Age Factors↗

Esophagography and esophagoscopy. Comparison in the examination of patients with head and neck carcinoma.

We carried out a prospective, double-blind study at three institutions, comparing esophagography with esophagoscopy for the detection of simultaneous cancer of the esophagus in patients with other squamous cell cancers of the head and neck. The goal was to determine whether esophagography and esophagoscopy are necessary for the examination of patients before treatment. One hundred eighty-two patients were studied; both examinations were done in 148 patients. Twenty-one patients could not undergo esophagoscopy; esophagography was inadequate in 9 patients; 4 patients could have neither examination. Concordance was noted between the two procedures in 86.5% of patients. Sixty-five percent were normal, and 21.5% were abnormal. One esophageal cancer was found in this series that was diagnosed by both methods. Our data suggest that esophagoscopy and esophagography may be complementary in evaluating squamous cell carcinoma of the head and neck in patients before treatment. Esophagography alone was useful in patients in whom esophagoscopy could not be performed.

Adult↗

The structure of aconitase.

The crystal structure of the 80,000 Da Fe-S enzyme aconitase has been solved and refined at 2.1 A resolution. The protein contains four domains; the first three from the N-terminus are closely associated around the [3Fe-4S] cluster with all three cysteine ligands to the cluster being provided by the third domain. Association of the larger C-terminal domain with the first three domains creates an extensive cleft leading to the Fe-S cluster. Residues from all four domains contribute to the active site region, which is defined by the Fe-S cluster and a bound SO4(2-) ion. This region of the structure contains 4 Arg, 3 His, 3 Ser, 2 Asp, 1 Glu, 3 Asn, and 1 Gln residues, as well as several bound water molecules. Three of these side chains reside on a three-turn 3(10) helix in the first domain. The SO4(2-) ion is bound 9.3 A from the center of the [3Fe-4S] cluster by the side chains of 2 Arg and 1 Gln residues. Each of 3 His side chains in the putative active site is paired with Asp or Glu side chains.

Aconitate Hydratase↗

Structure of activated aconitase: formation of the [4Fe-4S] cluster in the crystal.

The structure of activated pig heart aconitase [citrate(isocitrate) hydro-lyase, EC 4.2.1.3] containing a [4Fe-4S] cluster has been refined at 2.5-A resolution to a crystallographic residual of 18.2%. Comparison of this structure to the recently determined 2.1-A resolution structure of the inactive enzyme containing a [3Fe-4S] cluster, by difference Fourier analysis, shows that upon activation iron is inserted into the structure isomorphously. The common atoms of the [3Fe-4S] and [4Fe-4S] cores agree within 0.1 A; the three common cysteinyl S gamma ligand atoms agree within 0.25 A. The fourth ligand of the Fe inserted into the [3Fe-4S] cluster is a water or hydroxyl from solvent, consistent with the absence of a free cysteine ligand in the enzyme active site cleft and the isomorphism of the two structures. A water molecule occupies a similar site in the crystal structure of the inactive enzyme.

Aconitate Hydratase↗

Stomal varices: percutaneous transhepatic embolization.

Peristomal varices occasionally form in patients with chronic liver disease who have surgically created intestinal anastomoses and stomas. Hemorrhage from these varices carries an estimated mortality of 3%-4% per episode, as opposed to the 30%-40% mortality associated with gastroesophageal variceal bleeding. The cases of four patients who underwent transhepatic mesenteric vein catheterization with embolization of stomal varices for recurrent, intractable bleeding are presented. In three of the four patients there was no additional hemorrhage for at least 5 months. One patient was lost to follow-up. There were no complications. Since stomal variceal hemorrhage has a low mortality, transhepatic embolization is presented as a means of hemorrhage control when sclerotherapy fails and when shunt surgery presents an unacceptably high rate of morbidity and mortality relative to the underlying disease.

Aged↗

Radiology reports: assessment of a 5,000-word speech recognizer.

A prototype 5,000-word recognizer for the generation of radiologic reports by voice entry was evaluated. The system had a capacity sufficient enough to include all radiologic examinations and all desired words in one lexicon. The lack of such a capacity had been identified as a major limitation of a 1,000-word system previously evaluated. Overall reliability in word recognition was 98%. The device may be widely applicable for use in any radiology practice.

Hospital Information Systems↗

Crystal structure of Cd,Zn metallothionein.

The crystal structure of Cd,Zn metallothionein isoform II from rat liver has been determined using the anomalous scattering data from five Cd in the native protein. The structure of a 4Cd cluster was solved by direct methods. A 2.3 A resolution electron density map was calculated by an iterative solvent leveling and map inversion procedure. The structure is folded into two domains. The N-terminal domain (beta) of residues 1-29 enfolds a three-metal cluster of 1 Cd and 2 Zn coordinated by six terminal cysteine thiolate ligands and three bridging cysteine thiolates. The C-terminal domain (alpha) of residues 30-61 enfolds a 4Cd cluster coordinated by six terminal and five bridging cysteine thiolates. All seven metal sites have tetrahedral coordination geometry. The domains are roughly spherical, diameter 15-20 A; there is limited contact between domains. The folding of alpha and beta is topologically similar but with opposite chirality. Redundant, short cysteine-containing sequences have similar roles in cluster formation in both alpha and beta. The Cd1Zn2(cys)9 cluster is homologous with a 12 atom fragment of the Cd4(cys)11 cluster.

Animals↗