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Biomedical subjects

F Bloom

Publications and source records attributed to F Bloom.

At least 19 recordsLinked to original sources

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

Topographical study of the neurons containing hpGRF immunoreactivity in monkey hypothalamus.

Hypothalamic neurons producing growth hormone-releasing factor (GRF) have been characterized by immunohistochemistry in monkey hypothalamus, using an antiserum raised against hpGRF1-40, a peptide with GRF activity isolated from a human pancreatic tumor. Cell bodies with hpGRF immunoreactivity were found in arcuate and ventromedial nuclei. From these neurons, bundles of fibers innervate median eminence and appear to terminate in contact with portal vessels. In addition to median eminence, hpGRF immunoreactive fibers were found mostly in the anterior hypothalamus and the arcuate and ventromedial nuclei where they give perineuronal endings. These results correlate with earlier physiological data on hypothalamic control of growth hormone secretion and suggest that GRF is also involved in interneuronal relationships related or unrelated to neurohumoral control of pituitary secretions.

Animals

In vivo and in vitro effects of tetrahydroisoquinolines and other alkaloids on rat pituitary function.

Several tetrahydroisoquinolines (TIQs) were tested for their in vitro and in vivo capacities to modulate prolactin (PRl) and beta-endorphin (beta-end) secretion by the rat pituitary and for their abilities to displace [3H]spiroperidol and [3H]naloxone binding from pituitary and hypothalamic membranes. Receptor binding studies showed that TIQs could be classified as having (a) higher affinity for opiate receptors (tetrahydropapaverine, papaverine, 6-methylsalolinol, 1-carboxysalsolinol and 3',4'-deoxy-norlaudanosolinecarboxylic acid), (b) higher affinity for the dopamine receptor (salsolinol and 7-methylsalsolinol), or (c) approximately equal affinity for the two binding sites (6,7-dimethylsalsolinol and tetrahydropapaveroline, THP). In freely moving male rats, THP produced a several-fold increase in plasma PRL levels. This effect was not altered by co-administration of naloxone but was attenuated by dopamine. In vitro several TIQs reversed the inhibitory effect of dopamine on PRL secretion by cultured anterior pituitary cells. The order of potencies of the TIQs in this system paralleled their order of potencies in the dopamine receptor assay. THP, the most potent dopamine antagonist, also blocked dopamine-mediated inhibition of beta-endorphin secretion from neurointermediate lobe cells in culture. These data demonstrate that THP and some other TIQs can act as dopamine antagonists in radioreceptor assays, in cell culture and in vivo.

Animals

Event-related brain potentials are different in individuals at high and low risk for developing alcoholism.

Event-related brain potentials (ERPs) from normal drinkers with and without a family history of alcoholism were compared. Three separate groups of 10 subjects each (5 with and 5 without a family history of alcoholism) ingested either a placebo or ethanol at 0.56 or 0.94 g/kg. In each comparison, ERP components elicited in conjunction with subjects' decisions about task-relevant stimuli were of significantly reduced amplitude in individuals with a family history of alcoholism. Additionally, both the latency of the positive component and reaction times to correctly detected targets were significantly later in individuals with a positive history of alcoholism than in those without such a history. These group differences were apparent both with and without a challenge of alcohol. The data suggest that brain functions are different in individuals at high and low risk for the development of alcoholism (i.e., those with and without a family history of alcoholism, respectively).

Alcoholism

Blood alcohol levels in rats: non-uniform yields from intraperitoneal doses based on body weight.

1 Sprague-Dawley rats (n = 72) weighing from 125 to 450 g were injected intraperitoneally (i.p.) with 16% (w/v) ethanol to provide 1, 2 or 3 g/kg doses. 2 Resulting blood alcohol levels (BALs) demonstrated a general inadequacy of dose/body weight (g/kg) formulations of ethanol to provide uniform BALs in animals of different weights. 3 BAL differences between heavier and lighter rats were not well accounted for by developmental changes in liver weight or alcohol dehydrogenase activity. 4 From the data, a table was derived of more appropriate ethanol injection volumes to produce 0-300 mg% BALs (20 mg% increments) in rats from 100-500 g (10 g increments).

Animals

The regional distribution of gamma 3-melanotropin-like peptides in bovine brain is correlated with adrenocorticotropin immunoreactivity but not with beta-endorphin.

Immunoreactive (IR)-gamma 3-melanotropin (MSH), -adrenocorticotropin (ACTH) and -beta-endorphin in various areas of bovine brain were measured with their respective radioimmunoassays (RIA). The concentrations of IR-gamma 3-MSH were almost the same as those of IR-ACTH in most areas. Furthermore, in all brain regions, the concentrations of both peptides were lower than those of IR-beta-endorphin. The highest concentration of IR-gamma 3-MSH was found in hypothalamus, followed by thalamus, midbrain and striatum. Gel permeation chromatographic studies showed that the main gamma 3-MSH-like peptide in the hypothalamus, striatum and midbrain was a small form, whose molecular weight is about 4500. These brain gamma 3-MSH-like peptides were also found to be glycosylated.

Adrenocorticotropic Hormone

Distribution of opioid peptides in the pituitary: a new hypothalamic-pars nervosa enkephalinergic pathway.

The distribution of the endorphins, beta-endorphin and enkephalin (Met5-enkephalin and Leu5-enkephalin), was determined in the pars distalis, intermedia, and nervosa of the rat pituitary using both immunocytochemical and radioimmunological methods. Immunoreactive (ir) beta-endorphin was found in pars distalis and pars intermedia. On gel filtration of the pars distalis extracts, beta-endorphin immunoreactivity was eluted in three peaks corresponding to pro-opiocortin (5%), beta-lipotropin (75%), and beta-endorphin (20%). beta-Endorphin was the only component in the pars intermedia. Enkephalin was found in high amount in the pars nervosa. A new enkephalinergic hypothalamic-pars nervosa pathway was observed. Dehydration experiments on normal rats and analysis of the genetically polyuric Brattleboro rat suggest that this enkephalinergic pathway may modulate neurohypophyseal neurosecretion.

Animals