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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Coexistence of several unbalanced translocations in a case of neuroblastoma: the contribution of multicolor spectral karyotyping.

Spectral karyotyping (SKY) is based on the simultaneous hybridization of a set of 24 chromosome-specific DNA painting probes, each labeled with a different fluor combination. Automatic classification, based on the measurement of the spectrum for each chromosome, was applied to metaphases obtained from the affected bone marrow of a neuroblastoma case. Spectral karyotyping allowed the identification of chromosomal aberrations that could not be identified by the use of the G-banding technique, and revealed a number of gains and unbalanced translocations.

Child, Preschool↗
PubMed1999

The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point.

In this study, we searched for evidence for reactivation of three latent herpesviruses, Epstein-Barr virus (EBV), herpes simplex virus type-1 (HSV-1), and human herpesvirus 6 (HHV-6), in West Point cadets experiencing two different stressors. Blood samples were obtained from cadets before and after a 6-week training period known as "Cadet Basic Training" (CBT), at a baseline prior to final examinations, and then once again during the week of final examinations. Antibody titers to latent HSV-1, EBV, and HHV-6 were determined as a measure of the steady-state expression of latent virus. EBV virus capsid antigen (VCA) IgG antibody titers were unchanged in blood samples obtained prior to and immediately after CBT. However, EBV antibody titers were significantly higher in the blood sample obtained during examination week than in the baseline period before examination; they were also higher than antibody titers before/after CBT. None of the serum samples were positive for EBV VCA IgM antibodies, indicating that the changes in antibody titers to EBV were not associated with recent EBV infections in the class. No significant changes in antibody titers to HSV-1 or HSV-6 were found over the identical time periods, including examination week. Academic stress but not CBT modulated the steady-state expression of latent EBV, resulting in the reactivation of latent virus. The same stressors, however, did not affect the steady-state expression of latent HSV-1 or HSV-6, at least as measured by changes in antibody titers. The data provide additional evidence of the impact of different psychological stressors on the steady-state expression of latent herpesviruses.

Adult↗
PubMed1999

Baseline fruit and vegetable intake among adults in seven 5 a day study centers located in diverse geographic areas.

OBJECTIVE: To examine baseline rates of fruit and vegetable consumption among adults in the 5 A Day research trials in order to identify any regional and sociodemographic differences associated with daily servings. DESIGN: The main outcome measure was the frequency of fruits and vegetables consumed within 1 month of the baseline survey as assessed by a 7-item food frequency questionnaire (FFQ). SUBJECTS/SETTING: Participants (N = 15,060) were from 7 study centers. Study centers included schools (N = 48), worksites (N = 60), churches (N = 50), or the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinics (N = 15) in interventions to increase fruit and vegetable consumption. STATISTICAL ANALYSES: Means and standard errors, adjusting for clusters, were calculated. A mixed linear model analyzed relationships between fruit and vegetable consumption and regional center, gender, age, race, education, income, marital status, food-shopping responsibility, and whether one lives with children. RESULTS: Results indicate an overall mean intake of 3.6 daily servings of fruits and vegetables. Significant differences in mean daily servings were found among the regional study centers (low of 3.0 to high of 4.1). There were significant differences in mean daily consumption by age (< 30 years = 3.7 servings per day; 30 to 49 years = 3.4; > or = 50 years = 3.7), education (> high school = 3.4 servings per day; high school graduate = 3.4; some college = 3.5; college graduate = 3.9), race (black = 3.7 servings per day; Hispanic = 3.0; white = 3.6; other = 3.7), marital status (married = 3.6 servings per day; single = 3.5), and food-shopping responsibilities (little = 3.2 servings per day; about half = 3.6; most = 3.8). Only 17% of respondents ate 5 or more servings of fruits and vegetables per day. CONCLUSIONS: The 7 regions showed significant variability in daily fruit and vegetable consumption, suggesting that a single national message to increase fruit and vegetable consumption may not reach the population segments most in need of changing. It is advisable to spend more time understanding the food consumption habits of the population under investigation to develop messages to foster behavior change.

Adolescent↗
PubMed1999

Assessment of sternal vascularity with single photon emission computed tomography after harvesting of the internal thoracic artery.

OBJECTIVE: This study prospectively evaluates the effect on sternal vascularity of harvesting the left internal thoracic artery. METHODS: Twenty-four consecutive patients undergoing primary coronary artery bypass grafting were studied. One patient's procedure was altered during the operation, and he was eliminated from the study. The patients were prospectively randomized to receive a skeletonized internal thoracic artery (group I, n = 11) or a pedicled internal thoracic artery (group II, n = 12) graft. Each patient underwent a preoperative technetium 99 methylene diphosphonate bone scan using single photon emission computed tomography. The ratio of the mean counts per pixel on the left side of the sternum was compared with the mean counts per pixel on the right side. Postoperatively, all patients had a second scan, and sternal uptake was compared with the preoperative uptake. RESULTS: No significant differences in preoperative and operative variables were observed between the groups. A statistically significant reduction in blood flow to the left side of the sternum was shown postoperatively in group II compared with group I (0.61 +/- 0.11 vs 0.85 +/- 0.09; P <.001). Multivariable logistic regression analysis of preoperative and operative variables revealed only a pedicled left internal thoracic artery to be associated with a 20% or more reduction in left-to-right sternal activity ratio (odds ratio, 100; 70% confidence limits, 22-465; P =.002). CONCLUSION: A pedicled left internal thoracic artery graft to the left anterior descending artery reduces blood flow to the left side of the sternum during the acute postoperative period. This does not occur when the left internal thoracic artery is skeletonized.

Aged↗
PubMed1999

Amphibian declines: an immunological perspective.

Many, but not all, amphibian populations have been declining on all six continents on which they live. Although habitat destruction, direct application of toxicants, and introduction of predators/competitors are obvious causes of amphibian declines, many amphibians are dying of infectious diseases in relatively pristine habitats on several continents. In this paper, we review the patterns of these disease outbreaks and the characteristics of amphibian immune systems. Hypotheses are presented to explain the apparent susceptibility of amphibians to these pathogens. Natural and man-made factors that can alter amphibian immune responses to pathogens are discussed. Additional research is needed on the biology of the specific pathogens, the pattern of immune responses they elicit, and the nature of environmental stressors that may increase susceptibility to infectious disease.

Amphibians↗
PubMed1999

Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.

Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270). We have previously narrowed the TRMA locus from a 16-cM to a 4-cM interval on chromosomal region 1q23.3 (refs 3,4) and this region has been further refined to a 1.4-cM interval. Previous studies have suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. Here we identify the TRMA gene by positional cloning. We assembled a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region. This clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers and narrowed the locus to an approximately 400-kb region. Mutations in a new gene, SLC19A2, encoding a putative transmembrane protein homologous to the reduced folate carrier proteins, were found in all affected individuals in six TRMA families, suggesting that a defective thiamine transporter protein (THTR-1) may underlie the TRMA syndrome.

Amino Acid Sequence↗
PubMed1999

The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter.

Thiamine-responsive megaloblastic anaemia with diabetes and deafness (TRMA; MIM 249270) is an autosomal recessive disease thought to be due to a defect in thiamine (vitamin B1) transport. Pharmacological doses of thiamine correct the anaemia, and in some cases improve the diabetes, although progressive sensorineural deafness is irreversible. Previous studies localized the TRMA gene to a 4-cM region on chromosome 1q23.3 (ref. 5), and fine-mapping has recently narrowed that region further. We have previously demonstrated that fibroblasts from people with TRMA lack high-affinity thiamine transport. Expression of a gene encoding a known yeast thiamine transporter, THI10 (refs 8-10), in TRMA mutant cells prevents apoptotic cell death in thiamine-depleted medium. On the basis of these studies, we hypothesized that a defective thiamine transporter causes TRMA. We undertook a candidate gene approach to identify putative thiamine transporters in the 1q23.3 critical region. Here we present evidence that the gene SLC19A2 (for solute carrier family 19 (thiamine transporter), member 2) encodes the first known mammalian thiamine transporter, which we designate thiamine transporter-1 (THTR-1).

Amino Acid Sequence↗
PubMed1999

Atrichia with papular lesions resulting from a nonsense mutation within the human hairless gene.

Atrichia with papular lesions is a rare autosomal recessive form of alopecia characterized by hair loss soon after birth and the development during childhood of a diffuse papular rash. We have previously shown that this disorder results from a deleterious mutation in the human hairless gene, a gene also involved in the pathogenesis of a related but clinically distinct form of congenital alopecia, termed alopecia universalis congenita. In this report, we describe a novel nonsense mutation in exon 4 of the human hairless gene in a consanguineous kindred affected with atrichia with papular lesions. This report provides additional evidence for phenotypic heterogeneity among inherited atrichias and for an association between the papular rash of atrichia with papular lesions and nonsense mutations in the human hairless gene.

Alopecia↗
PubMed1999

Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.

Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the formation of a precursor and (2) the latter's subsequent conversion, by molybdopterin synthase, into the organic moiety of MoCo. These two steps are reflected by the complementation groups A and B and the two formally distinguished types of MoCo deficiency that have an identical phenotype. Both types of MoCo deficiency result in a pleiotropic loss of all molybdoenzyme activities and cause severe neurological damage. MOCS1 is defective in patients with group A deficiency and has been shown to encode two enzymes for early synthesis via a bicistronic transcript with two consecutive open reading frames (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene was mapped to 5q and comprises seven exons. The coding sequence and all splice site-junction sequences were screened for mutations, in MoCo-deficient patients in whom a previous search for MOCS1 mutations had been negative. In seven of the eight patients whom we investigated, we identified MOCS2 mutations that, by their nature, are most likely responsible for the deficiency. Three different frameshift mutations were observed, with one of them found on 7 of 14 identified alleles. Furthermore, a start-codon mutation and a missense mutation of a highly conserved amino acid residue were found. The locations of the mutations confirm the functional role of both ORFs. One of the patients with identified MOCS2 mutations had been classified as type B, in complementation studies. These findings support the hypothetical mechanism, for both forms of MoCo deficiency, that formerly had been established by cell-culture experiments.

Carbon-Carbon Lyases↗
PubMed1999

Identification of a genetic defect in the hairless gene in atrichia with papular lesions: evidence for phenotypic heterogeneity among inherited atrichias.

Recently, we showed that atrichia with papular lesions (APL), a rare inherited form of alopecia, is transmitted as an autosomal recessive trait in a large inbred kindred of Israeli-Arab origin. Furthermore, we mapped the APL locus to a 5-cM region of chromosome 8p12 in this family. The human "hairless" gene is a candidate target gene for the disease mutation because it maps to the APL locus and because it was recently found to be mutated in a related but clinically distinct form of alopecia known as "alopecia universalis" or "congenital alopecia." In the present study, the coding sequence of the hairless gene was compared by reverse transcription-PCR in fibroblast cell lines derived from an affected patient and an unrelated individual. We identified a single-base deletion (3434delC) in the hairless gene that cosegregated with the disease phenotype in the family. This deletion is predicted to cause a frameshift mutation in the highly conserved C-terminal part of the hairless protein, a region putatively involved in the transcription factor activity of the hairless gene product. The present results are indicative of phenotypic heterogeneity in inherited atrichias caused by mutations in the hairless gene, suggesting different roles for the regions mutated in APL and in other forms of congenital atrichia during hair development.

Age of Onset↗
PubMed1999

In vitro differentiation of a CD4/CD8 double-positive equivalent thymocyte subset in adult Xenopus.

The thymus is the major site of selection and differentiation of T cells in mammals and birds. To begin to study the evolution of thymocyte differentiation, we have developed, in the frog Xenopus, an in vitro system that takes advantage of cortical thymocyte antigen (CTX), a recently discovered T cell antigen whose expression is restricted to Xenopus cortical thymocytes. Upon transient stimulation with suboptimal mitogenic concentrations of the phorbol ester phorbol myristate acetate (PMA) plus ionomycin, Xenopus thymocytes are induced to differentiate into cycling T lymphoblasts that actively synthesize and express high levels of surface MHC class I and class II molecules. This appearance of T lymphoblasts correlates with a rapid down-regulation of both surface CTX protein and CTX mRNA. A thymocyte subset with an immature phenotype (CTX+, CD8+, class II- or class II low and class I-) was characterized by depleting class II+ cells or by panning with anti-CTX mAb. This immature CTX+ thymocyte subset displays a limited proliferative capacity compared to total, class II+ or to CTX- thymocytes, and can be induced, by PMA/ionomycin, to differentiate into more mature T lymphoblasts expressing surface class II and class I molecules. These results provide the first in vitro evidence in an ectothermic vertebrate of a conserved intrathymic pathway of thymocyte differentiation. In addition, our data reveal that CTX can serve as a differentiation surface marker of a population of immature thymocytes that appears to be the equivalent of the mammalian CD4/CD8 double-positive subset.

Animals↗
PubMed1999

Fibroblast growth factor receptor-3 as a marker for precartilaginous stem cells.

The epiphyseal organ contains two kinds of cartilage, articular and growth plate. Both enlarge during the growth phase of life. However, mitosis is not apparent in these tissues. In the current study, a search to trace the reservoirs of stem cells needed for the growth of these cartilages is done. A disorder in which the stem cells responsible for bone growth are mutated is achondroplasia; the mutation resides in the fibroblast growth factor receptor-3. Epiphyses stained with antifibroblast growth factor 3 antibodies reveal clusters of positively stained cells residing in the perichondrial mesenchyme, known as the ring of La Croix. Removal of the ring of La Croix causes a drastic growth arrest in the limbs of rat neonates. Cell cultures derived of the ring of La Croix biopsy specimens show high rates of cell proliferation and cell migration in vitro, in contrast to articular or growth plate derived chondrocytes. These cells stain intensely by antifibroblast growth factor receptor-3 antibodies and antiproliferative cells nuclear antigen, in contrast with articular and epiphyseal chondrocytes. Transfection of cells from the ring La Croix by an adenovirus vector containing the gene encoding for Escherichia coli beta-galactosidase (lacZ), allows tracing of these cells in tissues. Local injections were performed either to the ring of La Croix or to the joint cavity in a guinea pig model. A characteristic distribution was seen after injection. The transfected cells migrated to areas of bone and cartilage formation in the subchondral bone plate and on either side of the growth plate. This labeling and distribution is maintained for as many as 3 months after injection. The cells from the ring of La Croix appear to be responsible for bone growth. Furthermore, perichondrial cells and other precartilaginous cells expressing fibroblast growth factor-3 have been shown to be good cells for implantation to correct defects of articular cartilage.

Animals↗
PubMed1999

Lung exposure from inhalation of radon progeny: calculated from in vivo measurements of 210Pb in the skull.

To calculate the radiation dose to the lungs from the inhalation of radon and its short-lived progeny, an accurate estimate of cumulative exposure is necessary. In this preliminary study, the content of 210Pb in the skeleton is used to obtain a measure of integrated exposure to the lungs of people living in homes with above average concentrations of radon. Measurements of skeletal 210Pb made in vivo allow the exposed individuals to become, in effect, their own "samplers" and "dosimeters" through the normal physical and physiological processes of inhalation, deposition, and retention. 210Pb measurements have been made on 40 subjects whose homes have above average levels of radon. These data are used to obtain their cumulative lung exposures, defined as RLM (Respiratory Level Months). RLM is calculated from the numbers of atoms of RaA, RaB, and RaC,C' deposited in their respiratory systems over the time periods lived in the surveyed homes. The RLM values obtained are not significantly different than conventional WLM exposures calculated for the same time periods.

Adult↗
PubMed1999

Sulpiride versus metoclopramide in nononcologic patients with vomiting or nausea.

Metoclopramide, a benzamide substitute, is used frequently as an antiemetic drug. Sulpiride, another benzamide substitute, was investigated and found to be safe and effective in a handful of studies involving only oncologic or other severely symptomatic patients. In this investigation the authors compared prospectively the antiemetic efficacy of sulpiride versus metoclopramide in a double-blind, randomized study involving 36 nononcologic patients with transient vomiting or nausea of various etiologies. Each group of 18 patients received oral metoclopramide or sulpiride (10 mg or 50 mg respectively) every 8 hours for a total of three doses each (24 hours of treatment). A 5-point score was used to evaluate symptomatic relief. Efficacy of the two drugs proved similar, and at the end of the study, 14 and 13 of 18 patients on sulpiride or metoclopramide respectively were asymptomatic. Only transient, minor side effects were reported in one patient in each group. The authors conclude that sulpiride is an effective and safe antiemetic drug that can be adopted legitimately in such cases as a first choice, or serve as an equipotent alternative to metoclopramide in patients sensitive to the latter.

Adolescent↗
PubMed1999

Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts.

We have investigated the cellular pathology of the syndrome called thiamine-responsive megaloblastic anemia (TRMA) with diabetes and deafness. Cultured diploid fibroblasts were grown in thiamine-free medium and dialyzed serum. Normal fibroblasts survived indefinitely without supplemental thiamine, whereas patient cells died in 5-14 days (mean 9.5 days), and heterozygous cells survived for more than 30 days. TRMA fibroblasts were rescued from death with 10-30 nM thiamine (in the range of normal plasma thiamine concentrations). Positive terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining suggested that cell death was due to apoptosis. We assessed cellular uptake of [3H]thiamine at submicromolar concentrations. Normal fibroblasts exhibited saturable, high-affinity thiamine uptake (Km 400-550 nM; Vmax 11 pmol/min/10(6) cells) in addition to a low-affinity unsaturable component. Mutant cells lacked detectable high-affinity uptake. At 30 nM thiamine, the rate of uptake of thiamine by TRMA fibroblasts was 10-fold less than that of wild-type, and cells from obligate heterozygotes had an intermediate phenotype. Transfection of TRMA fibroblasts with the yeast thiamine transporter gene THI10 prevented cell death when cells were grown in the absence of supplemental thiamine. We therefore propose that the primary abnormality in TRMA is absence of a high-affinity thiamine transporter and that low intracellular thiamine concentrations in the mutant cells cause biochemical abnormalities that lead to apoptotic cell death.

Anemia, Megaloblastic↗
PubMed1999

A single sample subcutaneous luteinizing hormone (LH)-releasing hormone (LHRH) stimulation test for monitoring LH suppression in children with central precocious puberty receiving LHRH agonists.

The effectiveness of LHRH agonist therapy in central precocious puberty depends upon suppression of LH secretion. The iv LHRH stimulation test is the gold standard for evaluating LH suppression, but is difficult to administer because it requires an iv line and multiple blood samples. We hypothesized that a sc LHRH test followed by a single LH measurement 40 min later would be as accurate in the assessment of LH suppression in children receiving LHRH analogs. Eleven children received the sc test 1 month before or after their regularly scheduled iv LHRH treatment. Each child was receiving Lupron to suppress central puberty. Twenty-five comparisons of the iv and sc LHRH tests were completed over 14 months. We developed a clinical score for pubertal suppression using Tanner staging, skeletal maturation, and growth velocity. The best correlation between this clinical score and the iv LHRH test was achieved when biochemical suppression was defined as peak LH less than 2 IU/L (100% sensitivity, 95% specificity). Using this definition, the sc LHRH test was 96% accurate (in 24 of 25 subjects), with a sensitivity of 75% and a specificity of 100% compared to the iv LHRH test. We conclude that the single sample sc LHRH test can accurately determine LH suppression and adequacy of LHRH agonist therapy in central precocious puberty.

Adolescent↗
PubMed1999

Increasing fruit and vegetable consumption through worksites and families in the treatwell 5-a-day study.

OBJECTIVES: We report on the results of the Treatwell 5-a-Day study, a worksite intervention aimed at increasing consumption of fruits and vegetables. METHODS: Twenty-two worksites were randomly assigned to 3 groups: (1) a minimal intervention control group, (2) a worksite intervention, and (3) a worksite-plus-family intervention. The interventions used community-organizing strategies and were structured to target multiple levels of influence, following a socioecological model. Data were collected by self-administered employee surveys before and after the intervention; the response rate was 87% (n = 1359) at baseline and 76% (n = 1306) at follow-up. A process tracking system was used to document intervention delivery. RESULTS: After control for worksite, gender, education, occupation, race/ethnicity, and living situation, total fruit and vegetable intake increased by 19% in the worksite-plus-family group, 7% in the worksite intervention group and 0% in the control group (P = .05). These changes reflect a one half serving increase among workers in the worksite-plus-family group compared with the control group (P = .018). CONCLUSIONS: The worksite-plus-family intervention was more successful in increasing fruit and vegetable consumption than was the worksite intervention. Worksite interventions involving family members appear to be a promising strategy for influencing workers' dietary habits.

Adult↗