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Biomedical subjects

R Mack

Publications and source records attributed to R Mack.

At least 19 recordsLinked to original sources
PubMed2001

Pooled umbilical cord blood as a possible universal donor for marrow reconstitution and use in nuclear accidents.

Human umbilical cord blood has been shown to be an effective source of stem cells for marrow reconstitution in pediatric patients. Unfortunately, the quantity of stem cells obtained from an individual donor can be quite limited in both the total volume and the numbers of stem cells per ml of cord blood. HLA matching further limits the availability, but recent publications indicate close matching may be unnecessary. Therefore, if cord blood from different donors can be combined, larger numbers of stem cells can be available for clinical use provided pooling does not produce a negative effect. Storage of single cord blood specimens at 4 degrees C for 10-21 days in gas permeable bags produced an apparent increase in the percentage of immature cells (CD34, CD117, GPA) and mitotic activity (S+G2/M cells) over day 1. With similar storage of pooled specimens there was a further increase in the number of immature colonies cultured, CD34, CD117, GPA, S+G2/M cells. In addition, nucleated red blood cells increased over the mean values obtained from single cord blood samples. Our previous studies have indicated that large numbers of human mononuclear cells are necessary to reconstitute an irradiated animal model. By combining multiple samples of human cord blood, adequate numbers of stem cells could be pooled for use in adults and would provide cells for megadose therapy, including those patients that had accidentally received lethal irradiation.

Bone Marrow Transplantation↗
PubMed2001

Prevalence of CTLA-4 polymorphism A49G in Ashkenazi Jews.

Type 1 diabetes has been associated with numerous genetic loci. One locus, IDD12, includes the gene for cytotoxic T lymphocyte antigen (CTLA-4). A polymorphism at position 49 in the CTLA-4 gene, causing a substitution of Thr --> Ala, has been associated with various autoimmune diseases, including diabetes. The frequency of the polymorphism in European and Oriental populations has been recorded, but the frequency among different ethnic groups within the United States has yet to be established. In the present study, we analyzed 100 DNA samples from Ashkenazi Jews to determine the polymorphism's prevalence in that population. The A/A genotype was found in 49% of individuals, 41% were heterozygous A/G, and 10% possessed the G/G genotype. The prevalence of the A/A genotype in Ashkenazi Jewish population is the highest reported to date. The incidence of the homozygous G/G genotype within Spanish controls, 8.8%, is the lowest, followed by the Ashkenazi general population. The frequency of the non-diabetes-associated A/A genotype shows a similarity to the frequency of the diabetes-susceptible HLA haplotype, DR4-DQ8. The low prevalence of the autoimmune-associated G allele among Ashkenazi Jewish and Spanish populations may explain a lower than expected incidence of diabetes in HLA-susceptible populations.

Abatacept↗
PubMed2000

(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.

Acetylcholine↗
PubMed1999

Reliability of leg muscle electromyography in vertical jumping.

In this study we aimed to determine the reliability of the surface electromyography (EMG) of leg muscles during vertical jumping between two test sessions, held 2 weeks apart. Fifteen females performed three maximal vertical jumps with countermovement. The displacement of the body centre of mass (BCM), duration of propulsion phase (time), range of motion (ROM) and angular velocity of the knee and surface EMG of four leg muscles (rectus femoris, vastus medialis. biceps femoris and gastrocnemius) were recorded during the jumps. All variables were analysed throughout the propulsion and mid-propulsion phases. Intraclass correlation coefficients (ICC) for the rectus femoris, vastus medialis, biceps femoris and gastrocnemius were calculated to be 0.88, 0.70, 0.24 and 0.01, respectively. BCM, ROM and time values all indicated ICC values greater than 0.90, and the mean knee angular velocity was slightly lower, at 0.75. ICCs between displacement of the BCM and integrated EMG (IEMG) of the muscles studied were less than 0.50. The angular velocity of the knee did not correlate well with muscle activity. Factors that may have affected reliability were variations in the position of electrode replacement, skin resistance, cross-talk between muscles and jump mechanics. The results of this study suggest that while kinematic variables are reproducible over successive vertical jumps, the degree of repeatability of an IEMG signal is dependent upon the muscle studied.

Adult↗
PubMed1999

Inherited thrombophilia genes in minorities.

Mutations in several genes have recently been identified which predispose to thrombosis, specifically Factor V G1691A (Factor V Leiden), Prothrombin G20210A, and Methylene tetrahydrofolate reductase (MTHFR) C677T. The prevalence of these genes in European populations has been studied, but there is little data on their prevalence in minorities. Samples from a predominantly African-American population were analyzed for these mutations. While the G20210A mutation in the prothrombin gene and homozygosity for the C677T mutation of the MTHFR were not found in African-Americans, it appears that the carrier rate for the MTHFR C677T among Hispanics may be higher than in other reported groups.

Asian People↗
PubMed1999

The feasibility of using blood bank-stored (4 degrees C) cord blood, unmatched for HLA for marrow transplantation.

The main purpose for storing large numbers of umbilical cord blood (CB) units by cryopreservation is to obtain a close HLA match for use in bone marrow transplantation. The use of partially matched or unmatched CB has been suggested, and publications about the success of 3 antigen mismatches have given some credence to this suggestion. Graft vs host disease still is considered a major barrier for successful CB transplantation. The cost per frozen CB unit of approximately $15,000 considerably limits its availability in developing countries. Eleven human umbilical cord specimens were stored in gas-permeable bags at 4 degrees C for up to 3 weeks. Clonal growth, replating efficiency in methylcellulose cultures, differential count, and flow cytometric immunophenotyping results were examined at intervals up to 21 days. Mixed lymphocyte cultures were evaluated on 13 similarly stored specimens at intervals up to 14 days. When plated at 1, 10, and 21 days, the combined percentage of the more primitive colonies increased on days 10 and 21. Replating efficiency of blast cell colonies when stem cell factor was added was 81.2% and 67.8% on days 10 and 21, respectively. When mononuclear cells were immunophenotyped, the mean percentage of CD34+ and CD117+ cells, considered primitive stem cell markers, increased significantly from day 1 to day 21. The ability of stored CB cells to respond to phytohemagglutinin or alloantigens decreased progressively from day 1 to day 14. By day 14, the reactivity of CB responder cells, in mixed lymphocyte cultures, to fresh allogeneic CB stimulator cells declined significantly. These findings suggest that CB can be stored in existing blood bank facilities and retain its hematopoietic potential for transplantation. Furthermore, it may be feasible to combine individual CB samples to provide a sufficient number of viable stem cells for transplantation, substantially expanding the number of potential recipients.

Blood Banks↗
PubMed1998

Lack of CYP3A inhibition effects of sertindole on terfenadine in healthy volunteers.

The effect of sertindole (a new selective antipsychotic compound) on the pharmacokinetic disposition of terfenadine was investigated. Thirteen subjects who completed the study received a single 120 mg dose of terfenadine alone or with concomitant 20 mg sertindole daily. The mean values for terfenadine Cmax (alone: 2.42 +/- 1.48 ng/ml, in combination: 2.99 +/- 1.85 ng/ml) and AUC (29.6 +/- 18.9 vs 37.9 +/- 23.4 ng x hr/ml) did not change statistically significant in the presence of sertindole (p > 0.05). Similarly, the mean Cmax (531 +/- 195 vs 506 +/- 190 ng/ml) and AUC (3,728 +/- 1,163 vs 4,003 +/- 1,739 ng x hr/ml) values of carboxyterfenadine did not change statistically significant in the presence of sertindole (p > 0.05). The other pharmacokinetic parameters of terfenadine and carboxyterfenadine such as Tmax, t1/2, as well as the carboxyterfenadine to terfenadine Cmax and AUC ratios did not change in the presence of sertindole. Although terfenadine is a substrate for CYP3A (cytochrome P-450 3A), while sertindole is a substrate for both CYP2D6 and CYP3A4, the results in this study suggest that sertindole, at a clinical dose, is not an inhibitor of the metabolism of terfenadine.

Absorption↗
PubMed1998

Prevalence of factor V Leiden in African-Americans.

Factor V Leiden (FVL) refers to a mutation on the clotting factor, Factor V. Protein C is a factor involved in the fibrinolytic pathway. Activated protein C (APC) normally degrades activated Factor V. The presence of the Leiden mutation on Factor V makes this protein resistant to degradation by APC, leading to a hypercoagulable state. Previous studies reported a prevalence of FVL in various populations between 0-6% and absent in Africans. We studied two factor V alleles from one hundred random blood samples submitted for CBC. DNA was extracted, PCR was performed for wild-type allele and Leiden mutation with GH internal control for both reactions, and agarose gel electrophoresis was performed. Of 100 samples, five were heterozygous for FVL, which is in accord with other reports. Interestingly, four of 70 samples (5.8%) from African-Americans were positive for the mutation. The study indicates an apparent prevalence of 5% in the Newark, New Jersey population, including African-Americans.

Alleles↗
PubMed1997

Effects of food, antacid, and dosage form on the pharmacokinetics and relative bioavailability of sertindole in healthy volunteers.

The pharmacokinetic disposition and relative bioavailability of sertindole administered as a tablet dosage form under fasting conditions, in the presence of food, in the presence of antacid, and as solution was studied in a four-way crossover in young healthy male volunteers. Overall, tablet dosing after a meal or Maalox had no effect on t1/2 or AUC values when compared to fasting conditions, but increased the tmax and decreased the Cmax values slightly. The mean relative bioavailabilities of sertindole administered as tablets after fasting, with food, and with Maalox are 99, 104, and 98%, respectively, compared to sertindole solution. Therefore, sertindole can be administered with and without food and without regard to coadministration of antacids.

Administration, Oral↗
PubMed1997

Perceived risks to independent living: the views of older, community-dwelling adults.

The purpose of the present study was to gather the perceptions of older, community-dwelling adults about factors they considered essential for them to remain living within the community. In-depth interviews were conducted with 103 men and women over the age of 65 years who were living in their own home or apartment, within an urban center. Factors such as finances, health, family support, a sense of identity, and a feeling of independence were perceived by older adults to contribute to their ability to remain living in the community. Importantly, older adults viewed threats to this continued independent living as both (a) factors connected to losses and maintenance of capability, but also (b) as impediments to further growth of their personal well-being.

Activities of Daily Living↗
PubMed1997

Evaluation of a method for counting absolute numbers of cells with a flow cytometer.

We evaluated a method for performing absolute cell counts of lymphocyte populations with a flow cytometer. In this method, TruCount, test tubes that contain a known number of brightly fluorescent polystyrene beads are provided by the manufacturer. Whole anticoagulated blood is accurately pipetted into the tubes and mixed with fluorochrome-labeled monoclonal antibodies, the erythrocytes are lysed, and this mixture is analyzed on the flow cytometer. Absolute counts of lymphocyte subsets are calculated by determining the ratio of beads to the cell population of interest and then multiplying this ratio by the number of beads in the tube. We found this method to be reproducible. The values we obtained by the TruCount method were 5 to 10% higher than those obtained by conventional methods (flow cytometry and automated hematology) used to determine absolute numbers of cells. We believe that these differences are due to the methods of determining absolute cell counts and not to faulty identification of lymphocyte subsets.

Adolescent↗
PubMed1988

Prevalence and clinical correlates of non-Wenckebach, narrow-complex second-degree atrioventricular block detected by ambulatory ECG.

Among 113 patients with transient, narrow-complex second-degree atrioventricular (AV) block detected by ambulatory ECG, there were 20 with non-Wenckebach behavior. Based on the presence or absence of PR interval shortening after single blocked complexes, patients with narrow-complex non-Wenckebach patterns could be separated into a pseudo-Mobitz II group of 16 patients (greater than or equal to 20 msec of PR shortening after the blocked complex) and a classic Mobitz II group of four patients (constant PR interval). These groups had additional distinct ECG and clinical features. Patients with the pseudo-Mobitz II pattern had a 44% prevalence of associated Wenckebach block during the same ambulatory recording, whereas Wenckebach behavior did not occur in patients with classic Mobitz II block. Pseudo-Mobitz II block occurred at significantly longer cycle lengths (876 vs 585 msec) and with significantly longer PR intervals (225 vs 165 msec) preceding the blocked complex than did classic Mobitz II block. Syncope was the presenting symptom in 38% of patients with pseudo-Mobitz II block and in all patients with classic Mobitz II block. Patients with pseudo-Mobitz II block had a 56% prevalence of associated coronary disease and a 44% prevalence of congestive heart failure; the mortality rate was 38% in this group over 4 years of follow-up, but in all instances death was due to associated disease rather than to conduction itself. In contrast, patients with classic Mobitz II block had hypertensive or valvular disease but no evidence of coronary disease or congestive failure; all are alive with pacemakers after 3 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Physical disability and social liminality: a study in the rituals of adversity.

Sociological research on the disabled has for the past 25 years made extensive use of a social deviance model to characterize the status of the physically impaired. The present article, which is based on a three-year anthropological investigation of the social relations of paraplegics and quadriplegics in the New York metropolitan area, argues that there are shortcomings in the deviance model and offers, instead, a model taken from the anthropological study of ritual. The disabled are viewed as being in a 'liminal' state, as in the liminal phases of rites of passages. They are persons having an undefined status: they are neither ill nor well, neither socially alive and active nor socially expunged and removed. The status of the disabled in American society and the symbolism of disability in American culture are reexamined within this framework. This perspective is extended to other types of deep adversity, such as acute loss of income and status or catastrophic illness.

Activities of Daily Living↗