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R White

Publications and source records attributed to R White.

At least 343 records · Page 19Linked to original sources
PubMed1990

Physical mapping of probes within 14q32, a subtelomeric region showing a high recombination frequency.

The genetic linkage map of chromosome 14q32 contains 11 loci which span a distance of more than 60 cM. We have assigned 10 of these loci and the AKT1 proto-oncogene to segments of 14q32, using breakpoints derived from four independent chromosomal deletions or rearrangements. The most telomeric breakpoint was found in a proband (HSC 6) carrying a ring-14 chromosome. HSC 6 is monosomic for the distal part of 14q32, which contains the immunoglobulin heavy-chain locus (IGH), and random markers D14S20, D14S19, and D14S23. Two other chromosomal breakpoints, found in probands HSC 121 and HSC 981, could not be distinguished from each other using DNA probes, although the cytogenetic breakpoints appeared to be different at 14q32.32 and 14q32.31, respectively. The region between the breakpoints of HSC 6 and HSC 121 contains AKT1, D14S1, D14S17, and D14S16. The entire telomeric band 14q32 is assumed to contain about 10% of chromosome 14, or approximately 10 Mb. The 8 most telomeric loci, including D14S1, map to 14q32.32-qter, which measures only several megabases. However, these loci span a genetic distance of 23 cM. The high recombination frequency contrasts with the observation that two of the gamma genes in the IGH constant region show a high degree of linkage disequilibrium, though 180 kb apart. This finding suggests that a telomeric localization per se does not lead to a higher recombination frequency and favors the hypothesis that the higher recombination frequency at the telomeres may be due to specific "hot spots" for recombination.

Blotting, Southern↗
PubMed1990

A primary map of 24 loci on human chromosome 16.

A primary genetic map of chromosome 16 has been constructed by linkage analysis of 24 polymorphic loci, typed in 59 reference families. These loci form a continuous map that covers the whole chromosome and spans genetic distances of 187 cM in males and 226 cM in females. Most of the sex-specific recombination rate difference comes from a nontelomeric region that covers 10 cM in males and 74 cM in females. Both telomeric regions show the opposite trend, with a significant increase in the male recombination rate.

Chromosome Fragility↗
PubMed1990

Inhibition of estrogen receptor-DNA binding by the "pure" antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization.

Many estrogen-antagonist and -agonist ligands have been synthesized, some of which have proved clinically important in the treatment of hormone-dependent breast tumors and endocrine disorders. Here we show that the "pure" antiestrogen ICI 164,384 inhibits mouse estrogen receptor-DNA binding in vitro. The effects of this steroid on DNA binding can be overcome by addition of anti-receptor antibody whose epitope lies N-terminal to the receptor DNA-binding domain. Since this antibody is also capable of restoring DNA-binding activity to receptor mutants that either lack the dimerization domain or bear deleterious mutations within it, we propose that ICI 164,384 reduces DNA binding by interfering with receptor dimerization. In contrast, when complexed with the antagonist/partial agonist tamoxifen, the estrogen receptor is capable of binding to DNA in vitro, but tamoxifen does not promote the agonist-induced conformational change obtained with estradiol. The implications of these data are discussed in relation to the in vivo properties of these drugs.

Amino Acid Sequence↗
PubMed1990

A 22-amino-acid peptide restores DNA-binding activity to dimerization-defective mutants of the estrogen receptor.

We have identified residues within the estrogen receptor that are required for dimerization and high-affinity DNA binding. A 22-amino-acid peptide encompassing these residues was sufficient to restore DNA-binding activity to a mutant receptor lacking most of the hormone-binding domain. Point mutagenesis of the fusion protein confirmed that this sequence continued to mediate dimerization in a manner similar to that within the native receptor, although its position relative to the DNA-binding domain was appreciably altered.

Amino Acid Sequence↗
PubMed1990

National scientific registry of organ transplantation: data needs and uses.

There is a lot of work yet to be accomplished through the scientific registry, which will be made more efficient by the consolidation of information into patient-specific files rather than the existing "file by form" set-up. Additionally, users will be able to input data directly, eliminating the problem of the time delays between transplant and follow-up dates and the actual use of the forms. The registry data also will become more useful as the database grows. The data on long-term graft and patient survival will directly influence future policy decisions and transplant practices. The clinical outcomes of transplantation also will be influenced by donor management and organ preservation techniques, all of which can be addressed through the use of registry data. The ultimate goal is to make transplantation more reliable, more predictable, more widely available, and less expensive. The national, comprehensive database accomplishes that goal.

Forms and Records Control↗
PubMed1990

Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers.

We tested 132 individuals from 21 families segregating an allele for neurofibromatosis type 1 (NF-1), by using nine RFLPs tightly linked to the NF-1 locus. Family members had requested DNA testing either to determine whether "at risk" children were carrying the NF-1 allele or to determine whether their respective families would be informative for prenatal testing. Predictions about whether a child carries the NF-1 mutation were possible for all 32 at-risk offspring (greater than 98% accuracy based on the recombination estimates currently available for these DNA markers). At least one informative probe was available for all 23 matings in these 21 families; flanking markers were informative for 10 matings. Pairwise analysis showed that several of the polymorphisms were in tight linkage disequilibrium; few recombination events were observed with these markers in the families under study. We conclude that the DNA probes used in this study perform well for diagnostic testing of NF-1 in familial cases. A subset of five probe-enzyme systems (pHHH202/RsaI, p11-3C4.2/MspI, pTH17.19/Bg/II, p11-2C11.7/BamHI, and p11-2F9.8/TaqI) provide reliable linkage information for both clinical testing and prenatal diagnosis.

Alleles↗
PubMed1990

Amplification of a variable number of tandem repeats (VNTR) locus (pMCT118) by the polymerase chain reaction (PCR) and its application to forensic science.

A genetic locus (D1S58, defined by DNA probe pMCT118) that contains a variable number of tandem repeats (VNTR) has been successfully amplified from a very small amount of genomic deoxyribonucleic acid (DNA) by the polymerase chain reaction (PCR). The DNA sequence of the locus was determined and was found to consist of a 16-base consensus sequence and flanking sequences. Oligonucleotide primers complementary to the flanking sequences were synthesized to serve as primers for amplification of MCT118 by the PCR method. Human genomic DNA isolated from blood (2 ng from each sample) was successfully amplified at the MCT118 locus, and polymorphic bands were detectable by ethidium bromide staining after electrophoresis on polyacrylamide gels. Determination of genotypes at this VNTR locus can now be routinely achieved within 24 h, without the need for Southern blots or radioactive materials. Furthermore, the small size (387 to 723 base pairs) of the DNA fragments produced in the PCR amplification permits good resolution of individual alleles that differ by only one repeat unit. The precise specification of the number of tandem repeats present in each allelic fragment is reproducible from one analysis to another.

Alleles↗
PubMed1990

The trial of Abner Baker, Jr., MD: monomania and McNaughtan rules in antebellum America.

On the third of October 1845, in a small mountain community in Kentucky, Abner Baker, Jr., MD, was executed for the murder of his brother-in-law Daniel Bates. At the trial Baker's attorney argued unsuccessfully that at the time of the crime the accused suffered from monomania, a form of mental disease, and therefore should not be held responsible for the act. The trial bears historical significance by the fact that it took place only a year after the formation of the Association of Medical Superintendents of American Institutions for the Insane, the first professional organization of psychiatrists in the United States, and two years after the McNaughtan ruling in British jurisprudence which molded the insanity plea around the concept of "knowing right from wrong." Because it took place at this particular juncture in the history of both law and medicine, it provides a revealing portrait of how medical and legal concepts on insanity interacted with the indigenous social and political circumstances of antebellum America.

Bipolar Disorder↗
PubMed1990

Development of brachytherapy technique for nasal tumors in dogs.

Two groups of 4 dogs underwent nasal and ethmoidal turbinectomies followed by irradiation (mean minimal) doses of 5,390 and 6,550 cGy of radiation, respectively) from implanted intracavitary sources of iridium 192. Two dogs from each group were euthanatized for histologic evaluation at 3 months after irradiation. The remaining 2 dogs from each group were euthanatized for similar evaluation at 6 months after irradiation. During the course of the study, few clinical complications were encountered. Histologic evaluation of the tissues forming the nasal passages revealed loss of epithelial lining and fibrous tissue replacement of surrounding bone. A direct correlation of pathologic changes could not be associated with the amount of radiation received, but there seemed to be a tendency for greater change in those dogs given higher doses and those kept alive for 6 months.

Animals↗
PubMed1989

The N-ras oncogene is activated in a human medulloblastoma cell line.

Medulloblastoma is a malignant brain tumor of early childhood whose cells resemble the primitive neuroepithelial cells found normally in the developing nervous system. Medulloblastoma may be caused by mutational events affecting primitive neuroepithelial cells and preventing their differentiation into postmitotic neurons. The human ras genes, H-ras, K-ras and N-ras, are members of a family of proto-oncogenes that are targets for mutational changes that convert these normal genes into active, transforming oncogenes. Here we report that the N-ras oncogene is activated in the human medulloblastoma cell line TE 671 by a mutation at the third position of codon 61. A point mutation at this location corresponds to a substitution of histidine for glutamine in the N-ras gene product, p21. The oncogenic activation was shown by focus-formation in NIH 3T3 cell transfection assays. The location of the mutation was established using oligonucleotide hybridization assays enhanced through in vitro amplification of N-ras coding sequences using the Taq polymerase chain reaction. N-ras activation may be one of the mutational events that subvert normal neuroectodermal differentiation and lead to medulloblastoma in children.

Cell Transformation, Neoplastic↗