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Biomedical subjects

R Graham

Publications and source records attributed to R Graham.

At least 109 records · Page 6Linked to original sources
PubMed1993

Regulation of the phosphate (Pi) concentration in UMR 106 osteoblast-like cells: effect of Pi, Na+ and K+.

Osteoblast-like cells possess Na-dependent transporters which accumulate orthophosphate (Pi) from the extracellular medium. This may be important in bone formation. Here we describe parallel measurements of Pi uptake and cellular [Pi] in such cells from the rat (UMR 106-01 and UMR 106-06) and human (OB), and in non-osteoblastic human fibroblasts (Detroit 532 (DET)). In UMR 106-01, cellular [Pi] was weakly dependent on extracellular [Pi] and higher than expected from passive transport alone. [32Pi]-uptake was inhibited by Na deprivation, but paradoxically increased on K deprivation. With Na, 87 per cent of cellular 32P was found in organic phosphorus pools after only 5 min. Na deprivation also decreased cellular [Pi], in both UMR 106-01 and DET, but the decrease was smaller than that in [32Pi]-uptake. Ouabain decreased [32Pi]-uptake and cellular [Pi] in DET, but not in UMR 106-01. Regulation of cellular [Pi] is therefore at least partly dependent on Na/Pi co-transport, but this does not seem to be an exclusive property of osteoblasts.

Animals↗
PubMed1993

A transcription map of the region containing the Huntington disease gene.

A transcription map of the Huntington disease gene region was generated by a direct cDNA selection strategy using genomic DNA from the 4p16.3 region surrounding the D4S95 and D4S127 loci. A total of 58 cDNA fragments were obtained from cDNAs derived from fetal brain, frontal cortex, liver and bone marrow following hybridization to overlapping YACs from this region. These cDNA clones were aligned into transcription units by hybridization to specific mRNAs, by sequence overlap and by physical mapping onto overlapping YAC clones. Nine separate transcription units spanning approximately one megabase were detected by RNA hybridization. They represent a minimum number of genes in this region and do not include those genes expressed specifically in tissues not used for the hybridization. The transcription map that is provided by the cDNA segments will lead to the generation of a detailed gene map of this region.

Base Sequence↗
PubMed1993

Safety of intracavitary urokinase with percutaneous abscess drainage.

OBJECTIVE: Percutaneous drainage of abscesses is an effective treatment, but the success rate is lower for abscesses that have septa and are multilocular. Several clinical and in vitro studies suggest urokinase may be useful in such cases. Our study was designed to determine the safety of urokinase administered into an abscess cavity during the course of percutaneous drainage. SUBJECTS AND METHODS: Our study included 26 consecutive patients with 31 abscesses treated with percutaneous drainage. Exclusion criteria included age less than 18 or more than 95 years, CNS disorders (e.g., tumor, vascular problems), coagulation impairments, hepatic failure, pregnancy, and abscesses in the spleen, pancreas, or interloop area. Three doses were used: group 1 (nine patients), 1000 IU of urokinase per centimeter of abscess diameter; group 2 (11 patients), 2500 IU of urokinase per centimeter of abscess diameter; and group 3 (nine patients), 5000 IU of urokinase per centimeter of abscess diameter. These doses were administered every 8 hr for 3 days along with percutaneous drainage. Charts were reviewed to determine success and to detect adverse clinical events. Studies included sequential CT scans; serial serum determinations of hematocrit, prothrombin time, partial thromboplastin time, platelet count, fibrinogen levels, and levels of fibrin degradation products; and serial laboratory analysis of purulent material for fibrinogen and fibrin degradation products. Percutaneous drainage was considered successful if no surgical intervention was required. RESULTS: Our results showed no significant change in hematologic studies and no bleeding complications. Analysis of purulent material indicated that urokinase remained active in the abscess milieu. Drainage was successful in seven of 11 patients in group 1, all nine patients in group 2, and 10 of 11 patients in group 3. All eight abscesses with septa were successfully drained. CONCLUSION: Intracavitary urokinase can be given safely during percutaneous drainage of an abscess, with no associated bleeding complications or changes in coagulation parameters.

Abscess↗
PubMed1993

Active specific immunotherapy: PEM as a potential target molecule.

An understanding of the mechanisms involved in a biological phenomenon increases its potential for clinical exploitation. Thus, the simultaneous identification of TAA and the molecular mechanisms involved in antigen presentation and recognition by the immune system make the use of ASI a real possibility. The polymorphic epithelial mucin is expressed on most carcinomas and is highly immunogenic. Furthermore, it has many characteristics that make it potentially an ideal target molecule for ASI: (a) not only is it expressed, but it is upregulated by most carcinomas; (b) it is aberrantly glycosylated by carcinomas, resulting in the exposure of cryptic epitopes; (c) its tandem repeat structure results in there being many epitopes per molecule; (d) its extended structure at the surface means it is one of the first molecules the cells of the immune system encounter; and (e) its apparent ability to elicit HLA unrestricted killing already demonstrated in cancer patients makes it applicable to all individuals.

Amino Acid Sequence↗
PubMed1993

Entry of US medical school graduates into family practice residencies: 1992-1993 and three-year summary.

This is the 12th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each medical school's graduates entering family practice residency programs. Approximately 10.8% of the 15,466 graduates of LCME-accredited US medical schools between July 1991 and June 1992 were first-year residents in family practice in October 1992. This compares to 10.3% the previous year. This is the first increase since 1989. Medical school graduates from publicly funded medical schools were more than twice as likely to be first-year residents in family practice in October 1992 than were residents from privately funded schools, 13.8% compared to 6.4%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1992 at 18.3%; the Middle Atlantic and New England regions continued with the lowest percentages, 5.6% and 7.8%, respectively. Approximately one in two medical school graduates entering a family practice residency program as a first-year resident in October 1992 entered a program in the same state as that of his or her medical school of graduation. The percentages for each medical school have varied substantially from year to year since the AAFP has reported this information. The average percentage for each medical school for the last three years is reported. In addition, the number and percentage of graduates from colleges of osteopathic medicine who entered ACGME-accredited family practice residency programs are reported.

Accreditation↗
PubMed1993

Results of the 1993 National Resident Matching Program.

The 1993 NRMP results reveal a 19% increase in positions filled in family practice residencies compared to 1992 (2,002 versus 1,658) and a 17% increase in positions filled by US seniors (1,636 versus 1,398). Similarly, 11% more positions were filled on July 1, 1993, than 1992 (2,798 versus 2,530). This confirms a trend begun in 1992 of increased interest in careers in family practice, reversing four years of declining interest from 1988 to 1991. Two hundred one fewer US seniors matched in internal medicine, while 36 more chose pediatrics. Of students entering residency training in the generalist disciplines, it is expected that 27% of the class of 1993 (LCME-accredited medical schools) will practice as generalists. An increase of 9% of first-year positions offered, and the development of 15% new ACGME-accredited family practice residency programs, could accommodate 20% of the nation's graduates of LCME- and AOA-accredited medical schools. With increasing interest in careers in family practice, increased support for the nation's family practice residency programs is critical.

Career Choice↗
PubMed1992

Delineation of a 50 kilobase DNA segment containing the recombination site in a sporadic case of Huntington's disease.

No detectable rearrangements involving chromosome 4p16.3 have been observed in patients with Huntington's disease (HD). New mutations for HD could involve structural alterations which might aid the localization of the defective gene. We have reinvestigated a well documented sporadic case of HD. DNA haplotyping with markers between D4S10 and the telomeric locus D4S141 reveals a recombination event in one chromosome of the sporadic HD patient. The site of recombination maps within a 50 kilobase (kb) region, about 700 kb from the 4p telomere. Based on the extremely low HD mutation rate and significantly decreased recombination in the distal region of 4p, we hypothesize a direct link between the site of the recombination and HD in this patient.

Adult↗
PubMed1992

Cloning and mapping of the alpha-adducin gene close to D4S95 and assessment of its relationship to Huntington disease.

The genetic defect underlying Huntington's disease (HD) has been mapped to 4p16.3. Refined localization using recombinant HD chromosome analysis and allelic association analyses have identified two distinct candidate regions. Using a cDNA hybrid selection procedure we have cloned the gene for alpha-adducin, a subunit of a cytoskeletal protein crucial for spectrin-actin membrane plasticity. This gene maps to the proximal 2.2 Mb candidate region within 20 kb of D4S95. Alleles of markers at this locus have been shown to exhibit significant linkage disequilibrium with HD. A 4 kb alpha-adducin transcript was identified which is abundantly expressed in the caudate nucleus, the site of major neuronal loss in HD. Sequencing of the brain alpha-adducin cDNA from two HD patients and an age-matched control did not detect any sequence alterations specific to HD. However, we identified in brain cDNA of both patients and control samples, two alternately spliced brain exons, not previously described in the erythrocyte cDNA. A 93 bp exon is inserted in frame between codon 471 and 472 while a 34 bp exon inserted within codon 621 disrupts the frame and introduces a stop codon after 11 novel amino acids. The mapping of the adducin gene adjacent to D4S95 and its pattern of expression, as well as its potential for distinct alternately spliced variants, reinforces the necessity to accurately assess the role of the expression of this gene in the pathogenesis of HD.

Amino Acid Sequence↗