Search PubMed⌕ Search

Biomedical subjects

R White

Publications and source records attributed to R White.

At least 235 records · Page 13Linked to original sources
PubMed1994

Veterans' psychiatric benefits: enter courts and attorneys.

In 1988, the Veterans Judicial Review Act (VJRA) was signed into law, ending more than a century of Congressional measures that kept veterans' benefits claims completely out of the appellate court system. Before this new law, any decision made by the Department of Veterans' Affairs (VA) about a veteran's claim was final, and there was no recourse for independent judgment of an appeal. The legislation modified the existing Board of Veterans Appeals (BVA) to enhance its independence from the Veterans' Administration and established a new Court of Veterans Appeals (CVA) with jurisdiction to review BVA decisions. Veterans' benefits proceedings have not only been insulated from the courts, they also have been undesirable to private attorneys, because since 1864 Congress has prohibited attorneys from charging more than $10 to advocate a VA disability claim. The new law allows attorneys to represent veterans before the CVA and receive appropriate remuneration. In 1991, the number of veterans was estimated at 26,897,000, and VA disability compensation programs spent $9.6 billion. Currently, there are about 2,179,000 veterans receiving service-connected monetary compensation; approximately 13.5 percent (293,200) have a primary psychiatric disability. The CVA is a specialized Article I court that has seven justices and sits in Washington, D.C. In its formative years, the Court has reached decisions that have had an impact on the veterans' psychiatric benefits examination process. Now more than ever, non-VA psychiatrists may be asked to offer probative opinions in veterans' benefits proceedings. The authors review VA psychiatric disability procedures and, using case examples, discuss both precedent decisions involving VA psychiatric claimants and the evolving standards of judicial review.

Combat Disorders↗
PubMed1994

A radiation hybrid map of the BRCA1 region.

A locus on chromosome 17q, designated "BRCA1," has been identified as a predisposition gene for breast cancer. A panel of chromosome 17-specific radiation-reduced somatic cell hybrid clones has been assembled for high-resolution mapping of chromosome 17. A series of 35 markers, known to span the BRCA1 locus, were tested against this hybrid panel by PCR assays. Statistical analysis of these data yields a BRCA1 radiation hybrid map at a density sufficient to initiate YAC cloning and pulsed-field gel electrophoretic mapping of the candidate region. In addition, many of the markers reveal genetic polymorphisms and may be tested in breast cancer families and in loss-of-heterozygosity studies of sporadic breast cancers to better define the BRCA1 gene candidate region.

Animals↗
PubMed1994

Overpopulation.

Explore the source record for details and available documents.

Physician's Role↗
PubMed1993

Dimer formation by an N-terminal coiled coil in the APC protein.

Mutations in the human APC gene are associated with an inherited predisposition to colon cancer. APC codes for polypeptides of approximately 2800 amino acids, with sequence homologies to coiled-coil proteins in the first 900 residues. To determine the oligomerization properties of the APC protein, we used genetic and biochemical approaches to examine the ability of APC fragments to self-associate. A subdomain comprising the first 55 amino acids of APC was found to form a stable, parallel, helical dimer, as expected for a coiled coil. The location of a key dimerization element at the N terminus of the protein supports models in which mutations in APC exert effects through dimerization of the mutant gene products.

Adenomatous Polyposis Coli Protein↗
PubMed1993

A rapid screening method to detect nonsense and frameshift mutations: identification of disease-causing APC alleles.

A functional screen for nonsense and frameshift mutations has been devised that allows genes of interest to be scanned in segments. This assay is based on the cloning of these segments in-frame with a colorimetric marker gene (lacZ) followed by screening for the level of functional activity from the marker polypeptide (beta-galactosidase). Individuals at risk for any one of a number of genetic diseases, in particular familial adenomatous polyposis coli (APC), can be quickly screened for chain-terminating mutations introduced by stops and frameshifts. At present, scanning of the APC gene for mutation requires significant effort because it is a large gene and most APC mutations are unique. Therefore, this assay offers a powerful option for the diagnosis of this and other genetic diseases, as well as great potential for the development of a similar rapid screen to detect APC mutations in colorectal adenomas and carcinomas.

Alleles↗
PubMed1993

Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP).

beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

Animals↗
PubMed1993

Structure and function of the estrogen receptor.

The hormone binding domain of the estrogen receptor is required not only for binding estradiol but also to form stable homodimers of the protein and mediate transcriptional activation by the receptor. Residues that are essential for estrogen binding are also involved in dimerization, suggesting that the hormone-binding pocket is at or near the dimer interface. Distinct hydrophobic and charged residues are essential for hormone-dependent transcriptional activation, and these appear to be conserved by other members of the nuclear receptor family. We have found that the pure antiestrogens ICI 164384 and ICI 182780 increase the turnover of the receptor compared with that in the presence of estradiol. Because it is likely that the pure antiestrogens bind to a similar region of the receptor as that of estradiol, we propose that they inhibit receptor dimerization by means of their 7 alpha alkyl-amide extension. It appears that as a consequence nuclear uptake is inhibited and the receptor more rapidly degraded in the cytoplasm.

Animals↗
PubMed1993

1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene, an extremely potent modulator of mouse hepatic cytochrome P-450 gene expression.

We have investigated the effects of TCPOBOP (1,4-bis[2-(3,5- dichloropyridyloxy)]benzene), a potent cytochrome P-450-inducing agent [Poland, Mak, Glover, Boatman, Ebetino and Kende (1980) Mol. Pharmacol. 18, 571-580], on cytochrome P-450 isoenzyme expression in the mouse. Hepatic cytochrome P-450s from several distinct gene families were strikingly induced by a single dose of 75 micrograms of the compound. Northern-blot analysis demonstrated that this induction was almost certainly due to transcriptional activation of the cytochrome P-450 genes. The potency of this inductive effect was further reflected in the finding that cytochrome P-450 levels were still increased 12 weeks after a single injection of 75 micrograms of this compound. Interestingly, the mRNA levels of certain other genes, including those of metallothionein and the mouse major urinary proteins, were also induced. In view of the similarity in the effects of TCPOBOP and the synthetic glucocorticoid dexamethasone on mouse hepatic gene expression, we determined whether TCPOBOP acts through the glucocorticoid receptor. This did not, however, appear to be the case. Experiments with hypophysectomized animals demonstrated that TCPOBOP action was not regulated indirectly via the pituitary. In addition, induction of mouse Cyp2b protein by TCPOBOP in a primary culture of mouse hepatocytes suggests that the compound has a direct action on mouse liver. The above findings demonstrate that TCPOBOP is one of the most potent modulators of cytochrome P-450 gene expression described to date. It is not inconceivable that a single dose of this compound may alter hepatic gene expression for the majority of the lifespan of a mouse.

Animals↗
PubMed1993

Mosaic methylation in clonal tissue.

Current models suggest that de novo methylases add methyl groups to mammalian DNA early in development, establishing cell-specific patterns of methylation, and that these patterns are maintained by maintenance methylases that copy them onto newly replicated DNA strands. To test the prediction that clonal populations of histologically homogeneous cells should, therefore, have homogeneous methylation patterns, we studied methylation in leiomyomas. Despite the clonality and histological homogeneity of these solid tumors, we found that cells were heterogeneously methylated at a number of genomic sites. The heterogeneity was not caused by random methylation events within the leiomyomas because methylation patterns were similar in the core and periphery of a given tumor, and similar also among samples of independent leiomyomas and surrounding myometrial tissues extracted from a single uterus. Our results also showed that methylation of a site in the YNZ22 locus--in leiomyomas and in smooth muscle--was determined independently from the methylation of a neighboring site. Similar results were obtained for the IGH locus in colon and in several tumor tissues. These data indicate that methylation patterns are not identical in progeny cells, as current models suggest. Instead, it seems likely that methylation of a specific site reflects an equilibrium frequency defined by a continual loss and gain of methyl groups. Hence, the specificity found for the methylation of mammalian tissues is not achieved by strictly determining the methylation fate of individual cells, but by determining the overall methylation frequencies for individual sites.

Cell Differentiation↗
PubMed1993

An extended genetic linkage map and an "index" map for human chromosome 17.

Our previous genetic map for chromosome 17 has been expanded to include 72 loci defined by 90 RFLP markers and four microsatellite markers assayed by the polymerase chain reaction. Forty-one of these loci were ordered with odds greater than 1000:1 against local inversion, and the other 31 were ordered within 95% confidence limits. From the set of 41 unambiguously mapped loci, 14 well-spaced "index markers" can be extracted for efficient genetic studies. The complete map spans 173 cM (136 cM in males and 214 cM in females); average spacing between markers is 4.2 cM.

Animals↗
PubMed1993

Polymorphic SSR (simple-sequence-repeat) markers for chromosome 20.

Chromosome 20-specific simple-sequence-repeat (SSR) markers were developed from a flow-sorted phage library (LL20NS01), subcloned in Bluescript, and screened with a tetranucleotide repeat, (AAAG)6, to identify potentially polymorphic loci. Of 100 clones sequenced, 39 were selected to construct primers. Of these 39, 22 were polymorphic. Reference to the CEPH linkage database (version 5) permitted genetic mapping of 16 of the new markers to specific regions of chromosome 20. Ten of the SSRs showed heterozygosity indices (above 70%) that would qualify them as potential index markers.

Base Sequence↗
PubMed1993

Analysis of hepatitis C virus capsid, E1, and E2/NS1 proteins expressed in insect cells.

The baculovirus/insect cell expression system was used to express the capsid protein and glycoproteins (e1 and e2/NS1) of the hepatitis C virus (HCV). Each polypeptide domain was expressed individually using two different constructs varying at their carboxy termini in order to retain or delete hydrophobic domains that may be involved in membrane association. The capsid proteins were transported to the nucleus where they formed a single large crystal-like inclusion. The capsid proteins were phosphorylated in insect cells. The e1 and e2 polypeptides were present in both the soluble and insoluble cellular fractions. Deletion of a hydrophobic domain in the carboxy terminus of e2 resulted in the polypeptide becoming soluble but not secreted. Deletion of the carboxy terminus of e1 had no effect on solubility. Both e1 and e2 were glycosylated, with variable glycosylation of e1 giving rise to a series of polypeptides varying in apparent molecular weight. Co-infection of insect cells with viruses expressing e1 and e2 resulted in a complex that permitted the coimmunoprecipitation of e1 with antibodies to e2 and vice versa. Immunofluorescence staining of insect cells expressing e1 and e2 indicated that reactivity to e2 was more prevalent in anti-HCV positive human sera.

Animals↗
PubMed1993

Vascular access surgery as an outpatient procedure.

Construction of a vascular access site for hemodialysis has traditionally been done on an inpatient basis or more recently in a hospital operating room as a 1-day admission. Over 18 months we performed 49 vascular access procedures on 45 patients in a freestanding ambulatory surgical center. Four patients had an arteriovenous radiocephalic autogenous fistula constructed, 30 patients had a polytetrafluoroethylene (PTFE) prosthesis inserted as an arteriovenous bridge graft, 11 patients had a planned reconstruction of a previously placed graft, 1 patient had a false aneurysm corrected, 1 patient had a chronically infected graft removed, and 2 patients had a thrombectomy. All procedures were in the upper extremities except for one femorosaphenous PTFE graft and one excision of a false aneurysm in a thigh prosthesis. Only one patient, an 84-year-old woman, required hospitalization following the outpatient procedure because she was unable to care for herself. No postoperative infection had occurred at 1 month follow-up. A left upper extremity graft performed at another inpatient facility was removed because of infection. The protocol for outpatient vascular access surgery includes preoperative evaluation of the patient for determination of the access site within a week of operation; duplex scan of subclavian veins if central venous lines have been in place for more than 2 weeks; scheduling surgery for the afternoon or morning following routine hemodialysis; obtaining a hemoglobin level, serum/electrolyte study, and an ECG following the last hemodialysis; parenteral antimicrobial prophylaxis; local infiltration anesthesia with standby; a minimum of 1 hour of observation in the recovery room; and a repeat hematocrit study prior to discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Bilateral synovial cysts of the thoracic spine: a case report.

We report a case of bilateral synovial cysts of the thoracic spine. The patient presented with progressive, lower-extremity weakness and hypesthesia, culminating in complete paraplegia. This rare lesion should be considered when confronted with a patient with thoracic cord compression.

Aged↗