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B A Cohen

Publications and source records attributed to B A Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1998

An artificial cell-cycle inhibitor isolated from a combinatorial library.

Understanding the genetic networks that operate inside cells will require the dissection of interactions among network members. Here we describe a peptide aptamer isolated from a combinatorial library that distinguishes among such interactions. This aptamer binds to cyclin-dependent kinase 2 (Cdk2) and inhibits its kinase activity. In contrast to naturally occurring inhibitors, such as p21(Cip1), which inhibit the activity of Cdk2 on all its substrates, inhibition by pep8 has distinct substrate specificity. We show that the aptamer binds to Cdk2 at or near its active site and that its mode of inhibition is competitive. Expression of pep8 in human cells retards their progression through the G1 phase of the cell cycle. Our results suggest that the aptamer inhibits cell-cycle progression by blocking the activity of Cdk2 on substrates needed for the G1-to-S transition. This work demonstrates the feasibility of selection of artificial proteins to perform functions not developed during evolution. The ability to select proteins that block interactions between a gene product and some partners but not others should make sophisticated genetic manipulations possible in human cells and other currently intractable systems.

Binding, Competitive↗
PubMed1998

Prevalence of IgE-mediated food allergy among children with atopic dermatitis.

OBJECTIVE: There is a growing body of clinical and laboratory evidence to support the notion that food allergy plays a role in the pathogenesis of atopic dermatitis (AD). However, the incidence of IgE-mediated food allergy in children with AD is not well established. DESIGN: A prospective study to determine the prevalence of IgE-mediated food hypersensitivity among patients referred to a university-based dermatologist for evaluation of AD. SETTING: University hospital pediatric dermatology clinic. PATIENTS: A total of 63 patients with AD were recruited (35 male; 32 white, 24 African-American, 7 Asian). METHODS: Patients were assigned an AD symptom score (SCORAD) and were screened for food-specific serum IgE antibodies to six foods (milk, egg, wheat, soy, peanut, fish) known to be the most allergenic in children. The levels of food-specific serum IgE were determined by the CAP System fluoroscein-enzyme immunoassay (CAP); patients with a value >/=0.7 kIUa/L were invited for an additional allergy evaluation. Those with CAP values below the cutoff were considered not food allergic. Patients were considered to be allergic if they met one of the following criteria for at least one food: 1) reaction on food challenge; 2) CAP value more than the 95% confidence interval predictive for a reaction; 3) convincing history of an acute significant (hives, respiratory symptoms) reaction after the isolated ingestion of a food to which there was a positive CAP or prick skin test. RESULTS: A total of 63 patients (median age, 2.8 years; median SCORAD, 41.1) were recruited; 22 had negative CAP values (without a significant difference in age or SCORAD score, compared with the 41 with positive specific IgE values). Further allergy evaluation was offered to the 41 remaining patients; 10 were lost to follow-up and 31 were evaluated further. Of these, 19 underwent a total of 50 food challenges (36 double-blind, placebo-controlled, and 14 open), with 11 patients experiencing 18 positive challenges (94% with skin reactions). Additionally, 6 patients had a convincing history with a predictive level of IgE; 5 had a convincing history with positive, indeterminate levels of IgE; and 1 had predictive levels of IgE (to egg and peanut) without a history of an acute reaction. Overall, 23/63 (37%; 95% confidence interval, 25% to 50%) had clinically significant IgE-mediated food hypersensitivity without a significant difference in age or symptom score between those with or without food allergy. CONCLUSIONS: Approximately one third of children with refractory, moderate-severe AD have IgE-mediated clinical reactivity to food proteins. The prevalence of food allergy in this population is significantly higher than that in the general population, and an evaluation for food allergy should be considered in these patients.

Adolescent↗
PubMed1997

The determination of ice composition with instruments on cometary landers.

The determination of the composition of materials that make up comets is essential in trying to understand the origin of these primitive objects. The ices especially could be made in several different astrophysical settings including the solar nebula, protosatellite nebulae of the giant planets, and giant molecular clouds that predate the formation of the solar system. Each of these environments makes different ices with different composition. In order to understand the origin of comets, one needs to determine the composition of each of the ice phases. For example, it is of interest to know that comets contain carbon monoxide, CO, but it is much more important to know how much of it is a pure solid phase, is trapped in clathrate hydrates, or is adsorbed on amorphous water ice. In addition, knowledge of the isotopic composition of the constituents will help determine the process that formed the compounds. Finally, it is important to understand the bulk elemental composition of the nucleus. When these data are compared with solar abundances, they put strong constraints on the macro-scale processes that formed the comet. A differential scanning calorimeter (DSC) and an evolved gas analyzer (EGA) will make the necessary association between molecular constituents and their host phases. This combination of instruments takes a small (tens of mg) sample of the comet and slowly heats it in a sealed oven. As the temperature is raised, the DSC precisely measures the heat required, and delivers the gases to the EGA. Changes in the heat required to raise the temperature at a controlled rate are used to identify phase transitions, e.g., crystallization of amorphous ice or melting of hexagonal ice, and the EGA correlates the gases released with the phase transition. The EGA consists of two mass spectrometers run in tandem. The first mass spectrometer is a magnetic-sector ion-momentum analyzer (MAG), and the second is an electrostatic time-of-flight analyzer (TOF). The TOF acts as a detector for the MAG and serves to resolve ambiguities between fragments of similar mass such as CO and N2. Because most of the compounds of interest for the volatile ices are simple, a gas chromatograph is not needed and thus more integration time is available to determine isotopic ratios. A gamma-ray spectrometer (GRS) will determine the elemental abundances of the bulk cometary material by determining the flux of gamma rays produced from the interaction of the cometary material with cosmic ray produced neutrons. Because the gamma rays can penetrate a distance of several tens of centimeters a large volume of material is analyzed. The measured composition is, therefore, much more likely to be representative of the bulk comet than a very small sample that might have lost some of its volatiles. Making these measurements on a lander offers substantial advantages over trying to address similar objectives from an orbiter. For example, an orbiter instrument can determine the presence and isotopic composition of CO in the cometary coma, but only a lander can determine the phase(s) in which the CO is located and separately determine the isotopic composition of each reservoir of CO. The bulk composition of the nucleus might be constrained from separate orbiter analyses of dust and gas in the coma, but the result will be very model dependent, as the ratio of gas to dust in the comet will vary and will not necessarily be equal to the bulk value.

Ammonia↗
PubMed1997

The development of an outcomes management system for acute medical rehabilitation.

In 1993, Continental Medical Systems, Inc. (CMS), a provider of comprehensive medical rehabilitation, developed the Total Outcomes and Prediction Program (TOPP) to measure and evaluate key medical rehabilitation outcomes, quality indicators, and patient satisfaction at its 37 acute rehabilitation hospitals. The broad purposes of TOPP are to manage patient treatment, improve the cost-effectiveness of care, and provide outcomes reporting for managed care and other interested parties. The challenge was to develop a system which could measure, evaluate, and report medical rehabilitation patient outcomes in a way that could be easily understood by multiple audiences, including payers, accrediting organizations, physicians, patients and families, case managers, and CMS clinical staff. Using data from the Uniform Data System for Medical Rehabilitation database, CMS created descriptive outcomes reports for each hospital and for the corporation overall, including performance statistics, outcomes report cards, and quality report cards. These initial reports, as well as updates, quarterly reports, and special ad hoc requests, provide CMS corporate and hospital staff with statistically valid and reliable information to manage the outcomes of medical rehabilitation treatment. TOPP has assisted CMS with meeting accreditation standards for outcomes management and measurement and has been used in managed care contract negotiations. Future TOPP efforts will integrate resource use data, medical acuity and outcomes from acute, subacute, and outpatient rehabilitation levels into CMS' outcomes reporting system.

Activities of Daily Living↗
PubMed1997

Neurologic complications of HIV infection.

Neurologic symptoms are common in HIV-infected individuals, and they result from a wide range of etiologic agents, including HIV itself and opportunistic pathogens. Neurologic syndromes may be presenting features or may occur at any stage of infection, and they affect all levels of the neuraxis. The physician who cares for patients with AIDS must be prepared to recognize these neurologic complications to pursue aggressive diagnosis and, where possible, therapeutic interventions. The possibility of concurrent or unusual pathogens and atypical presentations make care of the AIDS patient with neurologic disease a challenging exercise that requires informed analysis and thoughtful clinical judgment.

AIDS Dementia Complex↗
PubMed1996

Prognosis and response to therapy of cytomegalovirus encephalitis and meningomyelitis in AIDS.

Effective diagnosis and treatment of cytomegalovirus infection of the nervous system in AIDS patients has been limited by a lack of sensitive diagnostic measures. Retrospective series suggest a poor prognosis for cytomegalovirus encephalitis with rapid mortality. Polymerase chain reaction amplification of cytomegalovirus DNA allows detection in CSF that appears specific for CNS infection. In this series of seven patients with CNS cytomegalovirus infection in AIDS, four patients responded to therapy. Serial determinations of cytomegalovirus DNA in CSF in five patients revealed persistent detection in two treatment failures and absence of detection in three responders on subsequent CSF samples. A prospective trial to determine optimal therapy and to confirm the utility of cytomegalovirus DNA in CSF as a marker of the course of cytomegalovirus infection in the CNS is warranted and should consider prior therapy for cytomegalovirus, prior opportunistic infections, and leukoencephalopathy as potential prognostic variables.

AIDS-Related Opportunistic Infections↗
PubMed1994

Panglobal distribution of a single clonal lineage of the Irish potato famine fungus.

More than 300 isolates of the Irish potato famine fungus, Phytophthora infestans, collected in 20 countries on five continents, were analyzed for genetic variation at the mating type and two allozyme loci. A subset of more than 200 isolates was also analyzed for DNA "fingerprint" variation. A surprising result was that a single clonal lineage dominated most populations worldwide. All of the variation within this lineage appeared to have arisen by mitotic recombination or by mutation. In addition to the most common clonal lineage, a number of different, but apparently closely related, lineages occurred in the United States and Canada. The low levels of gene diversity in the derived populations compared to the presumed ancestral population in central Mexico indicate that P. infestans went through extreme genetic bottlenecks during its dispersal. The genetic data are consistent with the hypothesis that the initial migration of P. infestans in the 1840s was from Mexico to the United States and that only a single genetic individual was transported to Europe and subsequently to the rest of the world. If this hypothesis is correct, then the Irish potato famine was caused by a single clonal genotype of P. infestans.

DNA Fingerprinting↗
PubMed1994

Cutaneous polyarteritis nodosa. Reports of two cases in children and review of the literature.

BACKGROUND: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of small- and medium-sized arteries that most often affects the kidneys, heart, and liver but can affect any organ system. A cutaneous form of PAN without visceral involvement, which follows a benign but often chronic course, has also been described. Both forms are rare in children. OBSERVATIONS: We describe two children with cutaneous PAN who were admitted to The Johns Hopkins Children's Center, Baltimore, Md, within a 1-week period. Both girls, aged 2 and 6 years old, presented with multiple, red, painful, edematous nodules on the extremities, face, and trunk. Dermatologic findings were accompanied by fever, arthralgias, and arthritis, but neither child had evidence of severe systemic disease. Skin biopsy specimens revealed necrotic small- and medium-sized muscular arteries with neutrophilic and eosinophilic infiltrate and fibrin thrombi. Both patients responded to treatment with prednisone. CONCLUSIONS: In children with cutaneous PAN, systemic symptoms may be present, but the lack of life-threatening complications distinguishes this relatively benign disease from systemic PAN.

Biopsy↗
PubMed1994

Herpes simplex type 2 in a patient with Mollaret's meningitis: demonstration by polymerase chain reaction.

We describe a patient with recurrent self-limited aseptic meningitis meeting the criteria for Mollaret's syndrome, in whom extensive serological investigation and cerebrospinal fluid analysis failed to reveal a specific cause. Using polymerase chain reaction techniques to amplify herpes simplex viral DNA, we were able to identify the presence of herpes simplex virus type 2 in the cerebrospinal fluid. The duration of clinical illness may have been shortened by treatment with intravenous acyclovir. We suggest that herpes simplex virus may be a more common cause of aseptic meningitis than has been demonstrated by current commonly available serological and culture techniques.

Adult↗
PubMed1994

Sweet's syndrome in children.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is a rare inflammatory disease of unknown cause characterized by painful, erythematous plaques and a dermal infiltrate of mature neutrophils. Associated systemic disease is a common finding in patients with Sweet's syndrome, and in fact determines the prognosis; therefore, the diagnosis of Sweet's syndrome warrants a thorough medical evaluation. We found only 17 reported cases of Sweet's syndrome in children. Two cases of Sweet's syndrome in children are presented; these cases are typical, except for the tibial pain in the first patient and the marked leukocytosis in the second patient. Both patients responded promptly to systemic corticosteroid therapy, although both had relapse.

Child, Preschool↗
PubMed1994

Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985-1992.

OBJECTIVE: To describe temporal trends in the incidence of human immunodeficiency virus (HIV)-related neurologic diseases in the Multicenter AIDS Cohort Study from 1985 to 1992. METHODS: The incidence rates of six neurologic disorders were examined: toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy, HIV dementia, and sensory neuropathy. Poisson modeling was used to test linear trends over time and the effects of progressive immunosuppression, antimicrobial prophylaxis, and antiretroviral drug therapy. RESULTS: There was an upward temporal trend in all incidence rates, except for HIV dementia. Progressive immunosuppression in the cohort explained all calendar trends except for sensory neuropathy, where an increasing temporal trend remained even after adjusting for CD4+ cell count, and for HIV dementia where a slight decline was noted, although the effects were not statistically significant. We noted a protective trend of antimicrobial prophylaxis on toxoplasmosis and cryptococcal meningitis, but, in contrast, use of antiretroviral agents was not protective against HIV dementia. Men receiving didanosine, zalcitabine, or stavudine were more likely to develop sensory neuropathy. CONCLUSION: Despite the earlier and more widespread use of antimicrobial and antiretroviral agents, neurologic conditions still occurred frequently in this cohort, with annual rates above 1.5 per 100 person-years for HIV dementia and sensory neuropathy. Sensory neuropathy seems to be increasing in incidence and HIV dementia declining slightly in this cohort. As the epidemic matures and more people with profound immunosuppression live longer, the overall incidence of HIV-related neurologic diseases can be expected to rise.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Onychodystrophy in lichen striatus.

Lichen striatus is a common childhood eruption, but only rare reports link cutaneous manifestations and onychodystrophy. We report a case of lichen striatus and onychodystrophy in a 12-year-old girl, only the eighth such patient in the dermatologic literature. Nail changes may precede the rash of lichen striatus and should be considered in the differential diagnosis of isolated nail dystrophy in children.

Child↗