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Biomedical subjects

R G Best

Publications and source records attributed to R G Best.

16 recordsLinked to original sources
PubMed1998

Donor leukocyte infusion for treatment of graft rejection post partially mismatched related donor bone marrow transplant.

Graft rejection following bone marrow transplantation is more common in patients who receive their grafts from alternative donors and whose marrow is T cell depleted. Rejection in these patients is mediated by persistent host cells that interfere with successful establishment of donor-derived hematopoietic recovery. We describe a patient with chronic myelogenous leukemia in accelerated phase who rejected a T cell-depleted bone marrow graft, 2 months following partially mismatched related donor bone marrow transplant. Unmanipulated peripheral blood donor leukocyte infusion, without additional chemotherapy or immunosuppressive therapy resulted in complete hematopoietic recovery. Cytogenetics and RFLP demonstrated hematopoietic donor chimerism. The patient did not develop graft-versus-host disease.

Adult↗
PubMed1997

Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction.

Molecular studies were performed on 101 cases of confined placental mosaicism (CPM) involving autosomal trisomy. The origin of the trisomic cell line was determined in 54 cases (from 51 pregnancies), 47 of which were also analyzed for the presence of uniparental disomy (UPD) in the disomic cell line. An additional 47 cases were analyzed for parental origin in the disomic cell line only. A somatic (postmeiotic) origin of the trisomy was observed in 22 cases and included the majority of cases with CPM for trisomy 2, 7, 8, 10, and 12. Most cases of CPM involving trisomy 9, 16, and 22 were determined to be meiotic. Fetal maternal UPD was found in 17 of 94 informative CPM cases, involving trisomy 2 (1 case), 7 (1 case), 16 (13 cases), and 22 (2 cases). The placental trisomy was of meiotic origin in all 17 cases associated with fetal UPD (P = .00005). A meiotic origin also correlated with the levels of trisomy in cultured chorionic villi samples (CVS) (P = .0002) and trophoblast (P = .00005). Abnormal pregnancy outcome (usually IUGR) correlated with meiotic origin (P = .0003), the presence of fetal UPD (P = 4 x 10(-7)), and the level of trisomy in trophoblast (P = 3 x 10(-7)) but not with the level of trisomy in CVS or term chorion. The good fit of somatic errors with the expected results could have been observed only if few true meiotic errors were misclassified by these methods as a somatic error. These data indicate that molecular determination of origin is a useful predictor of pregnancy outcome, whereas the level of trisomy observed in cultured CVS is not. In addition, UPD for some chromosomes may affect prenatal, but not postnatal, development, possibly indicating that imprinting effects for these chromosomes are confined to placental tissues.

Cells, Cultured↗
PubMed1995

Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual syndrome.

PURPOSE: To further investigate the efficacy of progesterone in the treatment of the symptoms of premenstrual syndrome (PMS). MATERIALS AND METHODS: From an initial cohort of 25 subjects diagnosed with moderate to severe PMS, 17 reproductive age females completed the 7-month, double-blind, placebo controlled trial using 200-mg vaginal progesterone suppositories. Multiple modalities for evaluating symptoms were employed, including the Spielberger self-evaluation rating, the Beck depression inventory, and the Hamilton anxiety scale. In addition, each subject was interviewed by a psychiatrist on a monthly basis; ovulation was determined monthly using a basal body temperature chart; serum hormonal assays included beta endorphin, progesterone, follicle stimulating hormone, luteinizing hormone, estradiol, and prolactin. RESULTS: Hormonal assays confirmed no differences between treatment and control groups. Overall scores on all test vehicles were likewise not significantly different between the two groups; however, in the subcategory of nervous symptoms, a significant improvement was found in symptoms relating to tension, mood swings, irritability, anxiety and lack of control. CONCLUSIONS: Metabolites of progesterone (pregnanolone and allopregnanolone) may play a physiologic role as anxiolytic agents, perhaps modifying mood and anxiety; the current study confirms the utility of twice daily, 200-mg progesterone vaginal suppositories, in the alleviation of some PMS symptoms relating to anxiety and irritability. Further evaluation may be warranted to ascertain which patients in the known heterogeneous PMS population may be most likely to benefit from such treatment.

Adult↗
PubMed1995

Maternal serum placental alkaline phosphatase level and risk for preterm delivery.

OBJECTIVE: The purpose of this study was to determine whether elevated midtrimester serum placental alkaline phosphatase levels are predictive of preterm delivery. STUDY DESIGN: By use of banked serum specimens from a sample of women who had received maternal serum alpha-fetoprotein screening, placental alkaline phosphatase values for multiples of the median were obtained from 270 mothers who had experienced a preterm delivery and from 1598 mothers of term, appropriate-for-gestational-age infants. Specimens were analyzed for placental alkaline phosphatase by means of a monoclonal antibody enzyme-linked immunosorbent assay. Logistic regression was used to determine whether placental alkaline phosphatase was associated with preterm birth, while potential confounders were controlled for. RESULTS: Women with placental alkaline phosphatase levels > or = 2.0 multiples of the median were significantly more likely to be delivered of a preterm infant in the current pregnancy compared with women with levels < 2.0 multiples of the median (odds ratio 2.9, 95% confidence interval 2.1 to 3.9). The likelihood of preterm birth increased significantly with higher multiples of the median (p < 0.001). CONCLUSION: Women with elevated placental alkaline phosphatase levels are at increased risk for preterm delivery. Additional studies are needed to evaluate the clinical utility of placental alkaline phosphatase testing as a means of identifying mothers at risk for preterm birth.

Adolescent↗
PubMed1994

Numerical chromosome abnormalities in spermatozoa of fertile and infertile men detected by fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) with single-color chromosome-specific probes was used to study the rates of disomy for chromosome 1, 16, X, and Y in sperm of fertile and infertile subjects. Diploidy rates were studied using a two-color cocktail of probes for chromosomes 17 and 18 in the same sperm samples. Two-color methodology was not available at the outset of the study. A total of 450,580 spermatozoa were studied from 21 subjects (9 fertile, 12 infertile). Significant differences were observed in the disomy rates between chromosomes with the highest frequency observed for chromosome 16 (0.17%) and the lowest for the Y chromosome (0.10%). No differences were observed between fertile and infertile subjects for either diploidy or disomy. Total disomy rates for chromosomes 1, 16, X and Y ranged from 0.34% to 0.84% among infertile subjects, and 0.32% to 0.61% among fertile subjects. Our data suggest that generalized aneuploidy in sperm is not a major contributor to unexplained infertility.

Aneuploidy↗
PubMed1991

Attitudes toward presymptomatic testing and prenatal diagnosis for adrenoleukodystrophy among affected families.

One hundred and thirty-six individuals with a family history of X-linked adrenoleukodystrophy (ALD) or adrenomyeloneuropathy (AMN) were given a questionnaire surveying their sociodemographic characteristics, knowledge of X-linked inheritance, and attitudes toward prenatal, presymptomatic, and carrier testing. Of the respondents, 68% indicated that they would use prenatal testing. Of these, 57.1% would terminate a pregnancy of a male fetus hemizygous for the ALD gene and 13.5% would reportedly choose to terminate a heterozygote female fetus. Presymptomatic testing would be used by 88.7% of respondents to test at-risk sons and carrier testing would reportedly be used by 95.4% of respondents to test their at-risk daughters. Respondents correctly answered an average of 61% of the questions testing understanding of X-linked inheritance. This indicates a strong interest in prenatal, presymptomatic, and carrier testing and a need for genetic counselors to provide information about these available tests and X-linked inheritance.

Adrenoleukodystrophy↗
PubMed1991

Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis.

Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital.

Adult↗
PubMed1991

Prospective evaluation of maternal serum human chorionic gonadotropin levels in 3428 pregnancies.

As part of a multicenter prospective study, second-trimester human chorionic gonadotropin and alpha-fetoprotein concentrations were evaluated. Data included maternal age, human chorionic gonadotropin level, alpha-fetoprotein level, weight, race, and pregnancy outcome of 3428 pregnancies at between 15 and 20 weeks' gestation. The results of the study indicate that human chorionic gonadotropin levels decrease as maternal weight increases, that weight-adjusted human chorionic gonadotropin levels for Oriental and black women are higher than for white or Hispanic women, and that twin pregnancies have higher human chorionic gonadotropin levels than singleton pregnancies. Of 255 pregnancies that did not have normal outcomes, 54 (21.2%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median and 26 (10.2%) had alpha-fetoprotein levels greater than 2.5 multiples of the median. Of 11 pregnancies with fetal aneuploidy, 6 (54.5%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median. It is concluded that in human chorionic gonadotropin screening programs for fetal Down syndrome, weight and race adjustments are necessary for accurate risk assessment.

Aneuploidy↗
PubMed1991

Maternal serum placental alkaline phosphatase as a marker for low birth weight: results of a pilot study.

In a pilot study, maternal serum was analyzed for placental alkaline phosphatase (PLAP) to evaluate the possibility of using PLAP values as a prenatal marker to predict low birth weight in neonates. Study subjects were selected from among women whose newborns were of low birth weight. These women were screened for maternal serum alpha-fetoprotein (MSAFP) between 15 and 20 weeks of gestation. Of the mothers of low-birth-weight neonates, 43% had PLAP values of 2.0 multiples of the median (MoM) or higher; only 22% of the mothers in the control group had such high values. The adjusted odds ratio was 2.6 (95% confidence interval, 1.1 to 6.5) and was not confounded by race, age, or weight. Odds ratios were improved by selecting more extreme cutoff values, with fewer cases identified as positive. In 14% of the cases of low birth weight, both MSAFP and PLAP values were elevated, compared with 5.6% of those in the control group. These data suggest that PLAP elevations, with or without measurements for MSAFP, may be a useful indicator during the second trimester of pregnancy for the risk of low birth weight.

Adult↗
PubMed1989

Utilization of amniocentesis and chorionic villus sampling by South Carolina women 35 years of age and older.

An increase in utilization of prenatal diagnosis was observed from 1985 to 1986 in South Carolina. The overall rate of 39.9% for 1986 is comparable with other areas of the U.S. Utilization was correlated with geographic residence, race, and referral source. While there was considerable variation in prenatal diagnostic test utilization between counties in South Carolina, overall utilization rates were reasonably high and continued to increase from 1985 to 1986. It will be interesting to see what effect CVS has on overall utilization rates as this new procedure becomes more established throughout the state.

Adult↗
PubMed1988

Sister chromatid exchange induction near the baseline with low doses of the alkylating agent CCNU.

Sister chromatid exchange (SCE) and cell-cycle kinetics were examined at near-baseline levels in human peripheral lymphocytes exposed to low doses of the potent SCE inducer 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), in vitro. A preliminary SCE dose-response curve was determined with a broad range of doses of CCNU using a single donor. SCE induction was approximately linear over the entire dose range from 5 to 200 microM CCNU. Cell cycle kinetics were retarded in a dose-dependent manner. A second dose-response curve from the same donor was constructed using several doses of CCNU between 0.5 and 10 microM to evaluate linearity and uniformity of SCE response near baseline levels. SCE induction was approximately linear between 1.0 and 10.0 microM CCNU. Finally, SCE and cell-cycle kinetics were examined in 12 donors at doses of 1.0, 5.0, and 10.0 microM CCNU to evaluate the reproducibility of near-baseline SCE induction over a range of subjects. Cell-cycle kinetics were retarded at all three doses with a highly significant increase in SCE frequencies at 5.0 and 10.0 microM CCNU. These data suggest that increases in SCE less than twice background can be reliable indicators of genotoxic exposure.

Cell Cycle↗
PubMed1988

Sister chromatid exchange in human lymphocytes exposed to ascorbic acid and the cancer chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

This study examines sister chromatid exchange (SCE) induction by ascorbate, a weak in vitro SCE inducer which acts through free radical intermediates, and low doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), a potent SCE inducer which acts primarily through DNA interstrand cross-links. A small dose-dependent increase in SCE was observed in human peripheral lymphocytes exposed to ascorbate in the 0.5-10 mM dose range for 59 hours, with significant slowing of cell cycle kinetics at concentrations at and above 5 mM. CCNU concentration was selected to approximate the maximal increase in SCE induced by ascorbate. SCE frequencies in cells exposed sequentially to both agents were not significantly different from expectations under an additivity-of-effect model based on SCE response to each agent individually. Despite clear differences in the types of lesions induced, ascorbate and CCNU appear to act independently to induce SCE in a manner consistent with, though not exclusive to, Painter's replicon cluster model.

Adult↗
PubMed1988

Variable sister-chromatid exchange response in human lymphocytes exposed in vitro to gossypol acetic acid.

Gossypol has potential for widespread use as a male oral antifertility agent in humans since it appears to be highly efficacious, with reversible spermatostatic effects and minimal side effects. Furthermore, it is both inexpensive and readily available. Therefore, a thorough understanding of gossypol's genotoxic potential is critical. Although genotoxicity studies have produced conflicting reports, increased sister-chromatid exchange (SCE) and DNA-strand breaks have been reported in human cells exposed to gossypol in vitro. In the present study, SCE was examined in purified human lymphocytes and whole blood cultures exposed to gossypol acetic acid at various concentrations in serum-free medium. A small but statistically significant increase in SCE was observed in pooled analysis of 7 donors in whole blood cultures exposed to 0.70 microM gossypol acetic acid (p less than 0.02). Individual analyses revealed only one donor with a significant SCE response (p less than 0.001). In subsequent experiments, exposure at higher doses had no effect on SCE frequencies. A small but significant increase in SCE was observed in ficoll/hypaque purified lymphocytes exposed to 0.07 and 0.70 microM gossypol acetic acid. Interpretation of SCE data with variable response is discussed.

Cells, Cultured↗