Biomedical subjects

Carol West

Publications and source records attributed to Carol West.

7 recordsLinked to original sources

PubMed2003

Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia.

We report here 2 patients with chronic nonspherocytic hemolytic anemia (CNSHA) and severe red blood cell (RBC) adenylate kinase (AK) deficiency. One of these patients, a boy of Spanish origin, exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. The other patient was a white, American infant born to parents who were first cousins; he also presented with neonatal icterus and anemia. In neither case was psychomotor impairment observed. The first patient was found to be a compound heterozygote for 2 different missense mutations, 118G>A(Gly40Arg) and 190G>A(Gly64Arg) (cDNA sequence first described by Matsuura et al, 1989). The second patient was homozygous for an in-frame deletion (GAC) from nucleotide (nt) 498 to 500 or nt 501 to 503 of the cDNA sequence, predicting deletion of either aspartic acid (Asp) 140 or 141. The crystal structure of porcine cytosolic AK was used as a molecular model to investigate how these mutations may affect enzyme structure and function.

Adenylate Kinase↗

PubMed2002

Polymorphisms in iron-responsive binding protein 2 and lack of association with sporadic Parkinson's disease.

Mice with targeted disruptions in the iron-responsive binding protein 2 (IRP2) gene accumulate iron in distinct regions of the brain and develop neurodegenerative characteristics resembling Parkinson's disease after 6 months of age. To determine whether polymorphisms in IRP2 predispose humans to Parkinson's disease (PD), we sequenced the IRP2 gene of subjects with sporadic PD and normal controls. Three polymorphisms which result in an amino acid change were identified: L159V, F272L, and T560I. The L159V and T560I polymorphisms, identified in an African-American PD subject, were found in the African-American population at an allele frequency of 0.102 (n = 1,236) and 0.111 (n = 1,228), respectively, and were not associated with an increased prevalence of PD. The F272L polymorphism was found in a normal 58-year-old, Caucasian subject whose father had PD, but it was not observed in 38 additional patients with sporadic PD. The F272L polymorphism occurred at an allele frequency of 0.0014 (n = 1,384) in the normal Caucasian population. Additional F272L heterozygous subjects identified in the normal population did not have a family or personal history of PD. We conclude that these IRP2 polymorphisms do not play an important role in the development of sporadic cases of PD. It remains to be determined whether other polymorphisms in IRP2 play a role in familial PD.

Aged↗

PubMed2002

Erythrocyte viability in blood salvaged during total joint arthroplasty with cement.

BACKGROUND: Erythrocyte salvage, the collection of a patient's blood shed from the surgical wound, is one aspect of blood management. Previous investigators have examined salvaged blood for content; however, to our knowledge, none have examined the viability of erythrocytes after exposure to the chemical and thermal reactions produced by motorized instruments and polymethylmethacrylate during surgery. The purpose of this study was to determine the viability of salvaged erythrocytes from patients undergoing primary total joint arthroplasty with cement. METHODS: Erythrocyte viability studies were performed on specimens from three subjects with use of a double isotope-labeling technique employing chromium-51 and technetium-99m. With use of a fresh blood specimen obtained prior to surgery and a specimen of salvaged blood that had been recycled, washed, and filtered with use of the Cell Saver, the viability of the Cell-Saver-processed erythrocytes, labeled with chromium-51, was calculated on the basis of the technetium-99m-labeled red blood-cell mass. RESULTS: The mean erythrocyte viability (and standard deviation) in blood salvaged with use of the Cell Saver was 88.0% +/- 3.8%. The standard of the American Association of Blood Banks for minimum erythrocyte viability in adequately cross-matched allogeneic blood or predeposited autologous blood is 70%. CONCLUSIONS: The high rate of viability of the erythrocytes in this study shows that the Cell Saver is a valuable adjunct to other blood management techniques for patients having total joint arthroplasty. We believe that the very high mean rate of erythrocyte viability and the extremely small standard deviation in our three subjects, as compared with the standards of the American Association of Blood Banks, made additional study subjects unnecessary.

Arthroplasty, Replacement↗

PubMed2002

Polymorphisms in glucosylceramide (glucocerebroside) synthase and the Gaucher disease phenotype.

BACKGROUND: Gaucher disease results from the accumulation of glucosylceramide (glucocerebroside) in tissues of affected persons. Patients sharing the same genotype present with widely varying degrees of lipid storage and of clinical manifestations. OBJECTIVES: To determine whether variation in the glucosylceramide synthase (UDPGlucose ceramide glucosyltransferase) gene, which encodes the enzyme that regulates the synthesis of glucocerebroside, could account for the variability and clinical manifestations. METHODS: Patients homozygous for the 1226G (N370S) mutation, the most common in the Ashkenazi Jewish population, were investigated. The exons and flanking sequences of the gene were sequenced using DNA derived from five very mild Gaucher disease patients and four patients with relatively severe Gaucher disease. RESULTS: One polymorphism was found in the coding region, but this did not change any amino acids. Seven other polymorphisms were found in introns and in the 5' untranslated region. Some of these were single nucleotide polymorphisms; others were insertions. The mutations appear to be in linkage equilibrium and none were found with a significantly higher frequency in either severe or mildly affected individuals. CONCLUSIONS: Mutations in the glucosylceramide synthase gene do not appear to account for the variability in expression of the common Jewish Gaucher disease mutation.

Gaucher Disease↗

PubMed1996

Commentary.

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Journal Article↗

PubMedDate not supplied

Polymorphisms in the 5' flanking region of the HFE gene: linkage disequilibrium and relationship to iron homeostasis.

We have discovered two single-nucleotide polymorphisms in the 5' flanking region of the HFE gene. These mutations are -970 T-->G and -467 C-->G, numbering from the ATG start codon. When a T was present at -970, a C was always found at -467. The C allele was the less common at nt -467 with a gene frequency of 0.31 in white subjects with wild-type HFE. Slightly lower gene frequencies were observed in a small number of Hispanic and African-American subjects and a slightly higher frequency in a few Asian subjects. The less common -467 mutation was found in almost 12 chromosomes that bore the 845G-->A (C282Y) mutation and was significantly more prevalent in chromosomes containing the 187C-->G (H63D) mutation. Although this mutation is near an HNF3B/HFH2 site, its presence did not seem to affect iron metabolism as judged by the serum ferritin or transferrin saturation levels. The tighter association of the -467 polymorphism with the C282Y mutation is consistent with other data that suggest that the C282Y mutation has occurred relatively recently and that the H63D mutation is considerably older.

5' Flanking Region↗

PubMedDate not supplied

Seeking candidate mutations that affect iron homeostasis.

Hereditary hemochromatosis is characterized by marked variation of expression of the defect: very few homozygotes with the C282Y/C282Y HFE genotype have full-blown clinical disease, a larger number show biochemical stigmata of iron overload, and some seem normal biochemically. The following candidate genes have been examined in detail to determine whether polymorphisms in them may be responsible for this variation: transferrin, transferrin receptor 1, transferrin receptor 2, ferritin-L, ferritin-H, IRP1, IRP2, HFE, beta(2) microglobulin, mobilferrin/calreticulin, ceruloplasmin, ferroportin, NRAMP1, NRAMP2 (DMT1), haptoglobin, heme oxygenase-1, heme oxygenase-2, hepcidin, USF2, ZIRTL, duodenal cytochrome b ferric reductase (DCYTB), TNFalpha, keratin 8, and keratin 18. The coding sequence, exon-intron junctions, and promoters of each of these genes was sequenced in DNA from 20 subjects: 5 HFE C282Y/C282Y with clinical disease, 5 HFE C282Y/C282Y with normal/low ferritin levels and no disease, 5 wt/wt with high ferritin and transferrin saturation, and 5 wt/wt normal controls. When coding or promoter polymorphisms were encountered, DNA from large numbers of ethnically defined subjects was examined for these polymorphisms and a relationship between their existence and abnormalities of iron homeostasis was sought. Only in the case of one transferrin mutation did we find a strong relationship between the polymorphism and iron deficiency anemia. The putative genes that affect the expression of HFE mutations remain elusive.

Amino Acid Substitution↗