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Biomedical subjects

F Bloom

Publications and source records attributed to F Bloom.

At least 19 recordsLinked to original sources

Neuroscience was not even a word: an interview with Floyd Bloom.

Floyd Bloom says that he grew up, surrounded by doctors and pills, in a drug store in Dallas, where his father and uncles were pharmacists. He is a natural storyteller, readily recalling the people and events that have shaped his career. His narrative skills were apparent as early as high school, where he was encouraged, partially on the basis of aptitude tests, to pursue a career in journalism or public relations, and to stay away from hard subjects like math and science. In college, he majored in German literature, although he pursued premedical studies in accordance with his father's wishes. During his medical school and residency experiences in St. Louis, he recounts, he always attempted to carry in his mind an organized way of explaining his academic and clinical activities to the professors and attending physicians that might quiz him. His subsequent research into the central nervous system similarly benefited from his ability not only to anticipate and formulate questions, the answers to which often required the development of new methods, technologies, and alliances, but also to place his findings in novel contexts where they could be conceptually appreciated and utilized. The prospect of telling good scientific stories was one of the factors that later drew Bloom to the position of Editor-in-Chief of Science magazine (1995-2000). While there, he was instrumental in widening the contexts in which the magazine presents science, and in shaping the ways that scientific information is electronically disseminated across the globe. Currently on sabbatical from Scripps, Floyd Bloom continues to explore, as CEO of a startup company in La Jolla, the entrepreneurial contexts in which his own research can be applied.

History, 20th Century↗

An Approximate Analytical Expression for the Probability of Attachment by Sliding.

The focus of this paper is on the flotation microprocess of attachment by sliding, considered to be an important microprocess in flotation separation. A detailed discussion is provided as to which forces are important for this microprocess during flotation deinking. By including the resistive force due to film drainage, the gravitational force, and the flow force between the bubble and particle, and accounting for both Stokes and non-Stokes flow conditions, a closed-form approximation for the probability of attachment by sliding (P(asl)) has been developed. The expression presented here is a function of fluid properties, bubble and particle physical properties, and the ratio of the initial-to-critical film thickness separating the bubble and particle (h(0)/h(crit)). Using this result, it is shown that P(asl) generally decreases with increasing h(0)/h(crit) and increases with increasing bubble and particle radii and particle density. However, local minima are observed. Additionally, the transition from Stokes to non-Stokes flow conditions results in an abrupt transition in the P(asl) predictions. Copyright 1999 Academic Press.

Journal Article↗

Exact and Approximate Expressions for Bubble-Particle Collision.

The flotation microprocess of collision is investigated and an exact expression for the probability of collision (Pc) is developed based on the intermediate flow of Yoon and Luttrell (1). This expression for Pc only assumes that the bubble and particle are spherical and that the particle radius is less than the bubble radius (i.e., Rp < RB). In addition to removing the requirement that Rp << RB, the influence of a particle settling velocity is also included in the model development. The expression for Pc is shown to be a function of three dimensionless groups: (i) the magnitude of the dimensionless particle settling velocity, ||G ||; (ii) the bubble Reynolds number, ReB; and (iii) the ratio of particle to bubble radius, Rp/RB. The probability of collision model is compared to available experimental data and good agreement is shown. A parametric study is also completed for 0 </= ||G || </= 1, 0 </= ReB </= 500, and 0.001 </= Rp/RB < 1. In general, Pc is independent of ReB when Rp/RB less, similar 0.03, the particle settling velocity is important for small values of Rp/RB, and Rp/RB dominates as Rp/RB --> 1. Copyright 1999 Academic Press.

Journal Article↗

Modulation of serotonin 5-HT3 receptor expression in injured adult rat spinal cord motoneurons.

The effects of sciatic nerve lesions on the expression of serotonin 5-HT3 receptor (5-HT3R) alpha subunit in motoneurons of the spinal cord was investigated by semi-quantitative immunohistochemistry. Following sciatic nerve crush, a significant reduction in density of staining in motoneurons was observed in longitudinal sections of the ventral horn at 3 and 15 days on the lesioned side when compared to the contralateral side (p<0.01). At 30 days after crush, after completion of sciatic nerve regeneration and reinnervation of peripheral targets, intensity of staining had returned to normal. Conversely, after sciatic nerve cut, a lesion that does not allow for target reinnervation, highly significant reductions were observed at 3, 15, 30 and 45 days. These results suggest a role for functional contacts with muscular targets in the maintenance of 5-HT3R expression in spinal motoneurons.

Animals↗

Description of the Genetic Analysis Workshop 11 Collaborative Study on the Genetics of Alcoholism.

Problem 1 of Genetic Analysis Workshop 11 consists of data from a family study of the genetics of alcoholism and related traits contributed by the six centers making up the National Institute for Alcohol Abuse and Alcoholism sponsored by the Collaborative Study on the Genetics of Alcoholism (COGA). The family data included 1,214 members of 105 pedigrees ascertained for having three or more individuals affected with alcoholism. Data available to workshop participants included clinical phenotypes, personality measures, smoking behavior, event-related potentials, platelet monamine oxidase B activity, and a genome scan of 296 markers.

Alcoholism↗

Exemplary programs on midlife women's health issues in managed care settings.

OBJECTIVE: To identify exemplary programs on midlife women's health issues that have been developed and implemented in managed care settings. METHODS: Members of The American Association of Health Plans (AAHP) were invited by mail to submit information on their exemplary programs on midlife women's health issues. AAHP and HealthPartners Research Foundation established 12 criteria by which to evaluate the programs submitted. Following telephone interviews with representatives of eligible programs, they were asked to complete an extensive survey about their successful practices. The Women's Health Task Force of AAHP then reviewed and evaluated every program submission and selected 4 model programs on midlife issues for women. RESULTS: The 4 model programs included the use of health assessment questionnaires to assist providers in identifying risk areas and patients' needs for information; group educational sessions focusing on midlife issues related to lifestyle and hormone replacement therapy; a module-based curriculum syllabus; and an osteoporosis disease management program. All groups utilize multidisciplinary teams to develop and promote educational programs. CONCLUSIONS: As study findings add to our knowledge of menopause treatment approaches and as new information and products become available, some managed care plans are using innovative channels of communication to keep women informed.

Female↗

Central analgesic actions of loperamide following transient permeation of the blood brain barrier with Cereport (RMP-7).

The bradykinin analog, Cereport (RMP-7), was designed to increase permeability of the blood brain barrier (BBB). Over the past several years it has been developed primarily as a means of increasing permeability of the blood brain tumor barrier, where early evidence indicated a particularly robust and reliable effect. The present series of experiments were intended to determine whether Cereport might also be used to increase delivery of pharmacological agents across the normal (i.e., non-tumor) BBB. This was accomplished by testing the ability of Cereport to enhance delivery of the peripherally acting opiate agonist, loperamide, to the brain, as evidenced by induction of a centrally mediated analgesic effect. Intravenous administration of a combination of Cereport and loperamide produced a significant analgesic effect (2-fold increase in response times) when animals were tested on a hotplate apparatus. Loperamide alone did not produce analgesia. An analysis of the time course of analgesia revealed a graded onset of analgesia which peaked at 30 min, maintained asymptote at 60 min, and began to diminish by 120 min following Cereport and loperamide administration. Finally, the analgesic effects of combining Cereport and loperamide were completely blocked when animals were pre-treated with the opiate antagonist naloxone, demonstrating that the analgesia was mediated through opiate receptors. Collectively, these results suggest that Cereport was able to increase delivery of loperamide across the BBB, allowing it to gain access to opiate receptors in the CNS to produce a centrally mediated analgesic effect. They therefore provide clear evidence that safe and well-tolerated doses of Cereport can increase permeability of the normal (i.e., non-tumor) BBB. Moreover, they provide the first evidence of a pharmacological effect specifically enabled by controlled (i.e., receptor-mediated) modulation of the BBB.

Analgesics↗

A Theoretical Model of Flotation Deinking Efficiency

The associated probabilities of each microprocess occurring in flotation deinking are employed in the development of a kinetic or population balance-type model of the overall flotation process. The overall model contains two kinetic constants: The first, k 1 , governs the overall probability of a free ink particle successfully being intercepted by and adhering to an air bubble; the second, k 2 , is a measure of the probability that a particle/bubble aggregate pair will become unstable and split to yield a "new" free ink particle. The solution to the kinetic model is presented in terms of k 1 and k 2 , which are themselves functions of system parameters such as bubble and particle physical properties (e.g., diameter, density) and fluid properties (e.g., viscosity, surface tension). From this solution, a definition of theoretical flotation efficiency is presented, as well as definitions of other system performance parameters, and selected predictions are displayed.

Journal Article↗

Latex versus iodinated contrast media anaphylaxis in the cardiac cath lab.

A 65-year-old man had bypass surgery 10 years previously with pulmonary artery catheter monitoring. Shortness of breath and mitral regurgitation necessitated repeat left and right heart catheterization using a pulmonary artery catheter. Before any iodinated contrast media exposure, the pulmonary artery catheter was inserted and within 2 min the patient developed anaphylaxis associated ventricular fibrillation. It was discovered that the pulmonary artery catheter used in the cath lab had a latex balloon and that the patient had been exposed to latex 10 years ago. Latex induced anaphylaxis is rarely considered in the differential diagnosis of patients with hypersensitivity reactions in the cath lab, intensive care unit, and operating room. The principal reason for failure to recognize the latex balloon as a potential allergen is that most health professionals are not aware that almost all pulmonary artery catheters contain a latex balloon. The risk of an allergic response to latex is 0.8% for the general population. Others at high risk include those who have had multiple surgical procedures and interventions with repeated latex exposure. Five to 10% of all U.S. health professionals and those performing household duties wearing latex gloves have an allergic response to latex. Latex hypersensitivity is an IgE dependent reaction, while iodinating contrast medium reaction is an IgE independent reaction. If latex hypersensitivity is suggested by pre-procedural history or if the patient falls into a high-risk group, pre-procedural skin testing and/or latex IgE radioallergosorbent (RAST) should be performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

NGF and anti-transferrin receptor antibody conjugate: short and long-term effects on survival of cholinergic neurons in intraocular septal transplants.

We describe a new molecular carrier system that allows for the transport of nerve growth factor (NGF) across the blood-brain barrier (BBB), as assessed by trophic effects on intraocular forebrain transplants that contain central cholinergic neurons. The carrier system involves monoclonal antibodies (OX-26) directed against the transferrin receptor, to which NGF molecules are covalently linked. Transferrin receptors are highly concentrated on brain blood vessels and participate in the transport of iron across the BBB. Host rats with septal transplants were divided into four groups, which received OX-26-NGF, OX-26, NGF or saline intravenously at 2, 4, 6 and 8 weeks after grafting. Half of the animals were killed directly after the final injection, whereas the other half were allowed to survive for an additional 5 months. Control experiments revealed that blood vessels in mature brain grafts in oculo contained large amounts of transferrin receptors. Covalent binding of NGF to the OX-26 antibodies did not impede OX-26 binding to CNS transferrin receptors, nor did conjugation affect the bioactivity of NGF. A time-dependent increase in host brain NGF levels was found after injection of OX-26-NGF into the tail vein. Host serum contained some NGF antibodies in the short-term OX-26-NGF group that had disappeared in the long-term group; host adrenals showed no differences in wet weight or norepinephrine or epinephrine whole tissue levels in any of the groups. As previously reported, the overall growth of intraocular septal transplants was approximately twice as great in the OX-26-NGF group relative to all other groups. This difference in final size persisted unabated for at least 5 months after the last injection. Furthermore, the significantly higher numbers of choline acetyl transferase immunoreactive neurons in transplants of OX-26-NGF-treated hosts also persisted during the 5-month postinjection interval. Taken together, the data suggest that the OX-26 conjugate may be a unique approach to permit passage of neurotrophin peptides into the brain in a biologically active form.

Adrenal Glands↗

Blood-brain barrier penetration and in vivo activity of an NGF conjugate.

Nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons of the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant of dementia in these patients and may therefore suggest a therapeutic role for NGF. However, NGF does not significantly penetrate the blood-brain barrier, which makes its clinical utility dependent on invasive neurosurgical procedures. When conjugated to an antibody to the transferrin receptor, however, NGF crossed the blood-brain barrier after peripheral injection. This conjugated NGF increased the survival of both cholinergic and noncholinergic neurons of the medial septal nucleus that had been transplanted into the anterior chamber of the rat eye. This approach may prove useful for the treatment of Alzheimer's disease and other neurological disorders that are amenable to treatment by proteins that do not readily cross the blood-brain barrier.

Animals↗

The V5A13.1 envelope glycoprotein deletion mutant of mouse hepatitis virus type-4 is neuroattenuated by its reduced rate of spread in the central nervous system.

Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of less than 0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 10(4.2) PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS.

Animals↗

DH11S: an Escherichia coli strain for preparation of single-stranded DNA from phagemid vectors.

A new E. coli strain DH11S [mcrA delta(mrr-hsdRMS-mcrBC) delta(lac-proAB) delta(rec1398) deoR rpsL srl- thi-/F'proAB+ lacIqZ delta M 15] has been constructed. Transformation of DH11S competent cells with any of several different phagemid vectors [pSPORT1, pBluescript II SK(+), pGEM11Zf(+)] results in the production of highly purified single-stranded DNAs upon the addition of M13KO7 helper phage. Contamination by double-stranded DNAs was observed with all the other studied strains (XL1-Blue, JM109, DH5 alpha F'IQ). The optimal yield of single-stranded DNA production was obtained when glycerol stocks made from stationary phase cells or single colonies from overnight ampicillin plates of DH11S containing the phagemid vector were infected with M13KO7 helper phage using a wide range (1 to 100) of multiplicities of infection. Five different pSPORT1 clones containing cDNA inserts of various lengths (0.3 kb to 2.0 kb) were compared using these four different bacterial strains. The use of strain DH11S results in the best yields and quality of single-stranded DNA. Therefore, DH11S appears to be the best all-around host for various applications that require single-stranded DNA such as DNA sequencing, in vitro mutagenesis and construction of subtractive cDNA libraries.

Coliphages↗

High resolution in situ hybridization to determine the cellular distribution of lymphocytic choriomeningitis virus RNA in the tissues of persistently infected mice: relevance to arenavirus disease and mechanisms of viral persistence.

By the application of in situ hybridization to thin sections of paraffin-embedded tissues we have been able to determine with high resolution the cell types containing lymphocytic choriomeningitis virus nucleic acid in the tissues of persistently infected mice. We confirm and extend previous observations of virus persistence in the brain, lung, liver, kidney, pancreas, thyroid and reticuloendothelial system. In addition, we demonstrate for the first time persistence of viral nucleic acid in specific cell types in the thymus, lymph nodes, testes and bladder, and the adrenal, parathyroid and salivary glands; the cell types infected were observed in several animals. In lymphoid tissue, viral nucleic acid was predominantly located in the T cell-dependent areas of the spleen and lymph nodes; it was also present in cells of the thymic medulla. This has important implications for the deficiency in T cell function observed in persistently infected mice. In the testes, viral nucleic acid was detected in spermatogonia but not differentiating spermatocytes and therefore, in this tissue at least, persistence is related to the state of differentiation of the cell. Endocrine and exocrine dysfunctions have been described in persistently infected mice and we report that the highest levels of viral nucleic acid were found in the adrenal gland. The infection of endocrine and exocrine tissue was not pantropic, specific cell types expressed viral nucleic acid in each tissue. In the adrenal cortex, cells of the zona reticularis and zona fasciculata but not the zona glomerulosa were positive, whereas in the adrenal medulla viral nucleic acid was predominantly localized to adrenalin-secreting cells. Infection of the renal tubules, transitional epithelium of the bladder and the ducts of the salivary gland indicates the likely sites of virus production for the dissemination of arenavirus infections.

Adrenal Glands↗

Nomenclature relating to restriction of modified DNA in Escherichia coli.

At least three restriction systems that attack DNA containing naturally modified bases have been found in common Escherichia coli K-12 strains. These systems are McrA, McrBC, and Mrr. A brief summary of the genetic and phenotypic properties so far observed in laboratory strains is set forth, together with a proposed nomenclature for describing these properties.

Alleles↗

Nucleotide sequence and cellular distribution of rat chromogranin B (secretogranin I) mRNA in the neuroendocrine system.

The mRNA of rat secretory-vesicle protein chromogranin B is abundant in brain, adrenal medulla, and anterior pituitary. The primary translation product predicted from the cDNA sequence of this 2,337-nucleotide transcript corresponds to a hydrophilic 655-residue protein preceded by a signal peptide. Both termini of the mature 75-kD protein show extensive similarity to other chromogranins; the more variable internal region is characterized by glutamic acid clusters and numerous pairs of basic residues. In rodent brain, mRNA accumulation starts around embryonic days 13-14 and peaks by postnatal day 20. In situ hybridization in brain sections shows that the mRNA is enriched in the hippocampal formation, the endocrine hypothalamus, the olfactory system, and in anatomically distinct structures in the pons-medulla.

Amino Acid Sequence↗