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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 307 records · Page 17Linked to original sources
PubMed1994

Extrarenal production of calcitriol.

Similar to the discovery of the VDR in nonclassical target tissues, the expression of 1 alpha-hydroxylase activity in immune cells, in the hematopoietic system, in tissues at early stages in development, in keratinocytes, and in the liver raises numerous questions about the physiological role of endogenous 1,25(OH)2D3 production. Extrarenal sources are regulated independently from the renal enzyme. The tight control of nonrenal 1 alpha-hydroxylase by physiological levels of calcitriol under normal circumstances and the total absence of regulation in several pathological states are consistent with 1,25(OH)2D3 synthesis having a local role rather than contributing to systemic calcitriol homeostasis. The simultaneous expression of vitamin D receptors, constitutive 1 alpha-hydroxylase, and inducible 24-hydroxylase activity in the same cell or in cells of the nearby environment suggests that they constitute a means for an in situ regulation of the response to vitamin D. Experimental evidence indicates that tissue-specific vitamin D microendocrine systems participate in transmural calcium transport, in normalizing serum calcitriol in chronic renal failure, in the control of hematopoiesis, in the modulation of the immune response, and in cellular growth and differentiation in a variety of cell types. A complete understanding of the physiological relevance of extrarenal calcitriol synthesis awaits cloning of the 1 alpha-hydroxylase and characterization of the molecular mechanisms modulating its expression.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1993

Molecular characterization of monoclonal CRIA-positive anti-arsonate antibodies derived from idiotype-negative mice bearing a light chain polymorphism.

We have elicited anti-arsonate antibodies bearing the major cross-reactive idiotype (CRIA) in a double congenic idiotype-negative strain (C.C58.AL-20) bearing a light chain polymorphism that has previously been shown serologically not to complement idiotype-positive heavy chains. Using the idiotype cascade (Ab1-->Ab2-->Ab3-->-->Ab1'), CRIA-positive antibodies were raised and monoclonal antibodies were isolated and characterized serologically and by nucleotide sequence analysis. Two types of idiotype-positive anti-arsonate antibodies were generated in the C.C58.AL-20 strain. One group of hybridomas used the canonical VH1.8 heavy chain gene segment with V kappa 10 variant light chains. A second group used a VHGAM3.8 heavy chain with V kappa 10 variant light chains. This latter heavy-light pairing has been observed in CRIA-like responses previously in BALB/c mice after idiotypic manipulation (or rarely after antigen alone). These studies demonstrate the plasticity of the immune response when manipulated with idiotype reagents as well as its structural variability. Additionally, they provide important insights into the potentials of idiotype vaccines.

Amino Acid Sequence↗
PubMed1993

Forward plasma membrane flow in growing nerve processes.

Nerve growth requires addition of new plasma membrane material, which is generally believed to occur at the growth cone. Local incorporation of a fluorescent lipid analog into the plasma membrane of fast-growing Xenopus neurites revealed an anterograde bulk membrane flow that correlated with neurite elongation. The rate of membrane flow depended on the position of the labeled membrane segment along the neurite, increasing with distance from the soma. This result suggests that new membrane in growing Xenopus neurites is added not at the growth cone but at the cell body and along the neurite.

Animals↗
PubMed1993

Dietary intake and circulating vitamin levels of rheumatoid arthritis patients treated with methotrexate.

The nutrient intakes and circulating vitamin levels of 32 patients with rheumatoid arthritis who were treated with methotrexate were evaluated over a 6-month period. Dietary data were obtained and blood was drawn prior to the initiation of and following 12 and 24 weeks of methotrexate therapy. More than 50% of the patients had food intakes providing less than 67% of the recommended dietary allowance for zinc, vitamin E, folic acid, pyridoxine, and magnesium. Patients 51 years or older had better nutrient intakes than patients less than 51 years. Of the patients, 22% consumed vitamin supplements at the time they were recruited for the study. Mean circulating vitamin levels measured over the 6-month period were within normal limits. Our findings agree with previously published reports that patients with rheumatoid arthritis, particularly the subpopulation taking methotrexate, consume diets that are marginal in some nutrients. Additional research needs to be done to identify more sensitive nutrient assays and to establish more definitively the nutrient needs of patients with rheumatoid arthritis taking several therapeutic agents.

Adult↗
PubMed1993

Neurofilaments move apart freely when released from the circumferential constraint of the axonal plasma membrane.

Squid giant axons were used to obtain axonal cytoskeletons that had been separated from the confines of their plasma membranes. To remove the plasma membrane, axoplasm was extruded from the giant axon directly into an artificial axoplasm solution (AAS). This procedure produces a smooth axoplasmic cylinder in which neurofilaments (NFs) are the most prevalent cytological elements. The NFs scatter light strongly and thus dark-field light microscopy can be used to quantify the volume occupied by these polymers. Measurements of the widths of the dark-field images of the axoplasmic cylinders showed that the cross-sectional area of the NF population increased by 60-110% (n = 8) between 1-100 min after plasma membrane removal, and then continued to increase more slowly for many hours. After 1,000 min, the cross-sectional area was 75-160% (n = 8) larger than at 1 min. These light microscopic measurements of axoplasm suggest that the NF population disperses to occupy a continuously increasing volume after removal of the plasma membrane and immersion in AAS. This inference was confirmed by quantitative ultrastructural studies of NFs in axoplasmic cross-sections, which demonstrated that the spacing between the NFs increased between 1-1,000 min after plasma membrane removal. Comparison of the NF density distribution after 1,000 min with a theoretical distribution calculated using the Poisson theorem indicated that the NFs dispersed randomly. These studies on NFs in isolated axoplasm suggest that ordinary thermal forces of Brownian motion are sufficient to move axonal NFs apart independently and thereby to disperse them. We propose that, in the intact axon, the dispersive movements of the NFs spread the NF cytoskeleton radially and expansively to fill out the cylindrical space contained by the axonal plasma membrane and its surrounding connective tissue elements.

Animals↗
PubMed1993

Disparate effects of phosphoramidon on blood pressure in SHR and DOCA-salt hypertensive rats.

Phosphoramidon inhibits both endothelin converting enzyme (ECE) and neutral metalloendopeptidase (NEP). The contribution of ECE and NEP inhibition to the antihypertensive effects of phosphoramidon was investigated in SHR and DOCA-salt hypertensive rats. SCH 32615, an active acid of the potent and selective NEP inhibitor prodrug SCH 34826 was used as a reference compound. Intravenous infusion of SCH 32615 (1.0 mg/kg/min x 2 hr) or phosphoramidon (0.3 and 1.0 mg/kg/min x 2 hr) did not reduce blood pressure (BP) in conscious SHR. The combination of SCH 32615 (100 mg/kg + 1.0 mg/kg/min) and phosphoramidon (0.3 mg/kg/min) also did not alter BP in SHR. In comparison, the BP of conscious DOCA-salt rats was significantly reduced by phosphoramidon (0.01, 0.1 and 1.0 mg/kg/min x 2 hr) (-28 +/- 6, -51 +/- 5 and -85 +/- 6 mmHg, respectively). SCH 32615 (100 mg/kg, i.v.) over 5 min followed by a sustained infusion of 1.0 mg/kg/min for 2 hr also reduced BP by 49 +/- 7 mmHg (P < .05) in DOCA-salt rats. However, phosphoramidon (0.1 mg/kg/min x 2 hr) failed to cause a further reduction in BP in DOCA-salt rats concurrently receiving SCH 32615. In contrast, a higher dose of phosphoramidon (0.3 mg/kg/min) in combination with SCH 32615 caused a greater reduction in BP in DOCA-salt rats than SCH 32615 alone. In anesthetized normotensive rats, phosphoramidon (0.01-1.0 mg/kg/min x 30 min) dose-dependently inhibited the BP responses to big endothelin-1 (BET-1) without blocking the pressor responses to ET-1. SCH 32615 failed to attenuate the pressor responses to either BET-1 or ET-1. The results indicate that SCH 32615 lacks in vivo ECE inhibitory activity. It is concluded that the antihypertensive action of SCH 32615 and low doses of phosphoramidon can be attributed to the inhibition of NEP which may presumably cause an accumulation of ANF. In comparison, at higher doses phosphoramidon causes a further reduction of BP in DOCA-salt hypertensive rats by inhibition of endothelin bioconversion.

Animals↗
PubMed1993

Detection of Lewy bodies in Trisomy 21 (Down's syndrome).

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropathological diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a clinico-neuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neurohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Adult↗
PubMed1993

Histochemical and immunocytochemical study of ubiquitinated neuronal inclusions in amyotrophic lateral sclerosis.

Ubiquinated cytoplasmic inclusions are a characteristic feature of the anterior horn cell pathology of amyotrophic lateral sclerosis. The underlying abnormality leading to the production of these inclusions in this neurodegenerative motor system disease is unknown. Despite the application of a wide range of histochemical and immunocytochemical techniques we have been unable to identify a core constituent protein in these intraneuronal inclusions. A novel approach to this problem is required.

Amyotrophic Lateral Sclerosis↗
PubMed1993

The immunogenicity of hookworm (Necator americanus) acetylcholinesterase (AChE) in man.

A number of different but complementary approaches have been used to demonstrate the immunogenicity of Necator americanus acetylcholinesterase to infected individuals. Western blotting of parasite somatic extracts with human post-infection sera and a specific rabbit antiserum to AChE resulted in the development of almost identical antigen-recognition profiles. AChE-containing fractions produced by preparative iso-electric focusing were subsequently shown to be antigenic in ELISA using post-infection sera. This preliminary data was reinforced by the affinity purification of AChE by immobilized post-infection IgG, and the immunoprecipitation of AChE activity from ES by post-infection IgG. Finally, AChE purified by affinity chromatography on edrophonium chloride was shown to be antigenic by Western blotting, and in ELISA, against post-infection sera, although a degree of re-activity was also seen with normal human sera. This data is discussed in the context of the host-parasite relationship.

Acetylcholinesterase↗
PubMed1993

Properties of the genus Tatlockia. Differentiation of Tatlockia (Legionella) maceachernii and micdadei from each other and from other legionellae.

The biochemical reactions, carbohydrate content, and 16S-rRNA sequences of Tatlockia (Legionella) maceachernii and Tatlockia micdadei strains were studied. Except for catalase activity, Tatlockia strains were relatively inert in the biochemical tests commonly used in clinical laboratories. Phenotypically, the two Tatlockia species could be distinguished from other legionellae by the presence of yersiniose A, by their inability to hydrolyze hippurate or starch, by the absence of colony or media fluorescence, and by the absence of distinct browning of tyrosine-containing medium. These two species differed from one another by the production of acetoin by T. micdadei but not by T. maceachernii. Gelatinase activity, which had been reported in T. maceachernii, was observed in only one of the four strains studied. The 16S-rRNA sequences and carbohydrate profiles of T. maceachernii and T. micdadei were essentially identical. In preparing the RNA for study, it was noted that the 23S rRNA was fragmented in all T. maceachernii strains tested, while the 23S rRNA of T. micdadei strains was intact. Among the legionellae studied, T. maceachernii was most closely related to T. micdadei.

Bacterial Typing Techniques↗
PubMed1993

Composite microtubules of the axon: quantitative analysis of tyrosinated and acetylated tubulin along individual axonal microtubules.

We have shown previously, using immunoelectron microscopy, that axonal microtubules (MTs) are composite, consisting of distinct domains that differ in their content of tyrosinated alpha-tubulin (tyr-tubulin). Here, we extend these studies using a novel preparation that permits visualization of individual axonal MTs over distances of several tens of micrometers using conventional immunofluorescence procedures. Neurons are cultured on a substratum of poly-lysine and laminin and then extracted with a MT stabilizing solution containing Triton X-100 and NaCl. These extraction conditions cause a loosening of the axonal MT array so that individual MTs separate from each other for variable distances along their length. We call this phenomenon fraying. Within the axon shaft, individual MTs can often be traced for several tens of micrometers, but fraying is most extensive in the distal 100-200 microns of the axon, where individual MTs can frequently be traced for distances of 50 to 100 microns or more to their plus ends. In some cases MTs separate completely from the axon, permitting visualization of both of their ends. Double-staining of frayed preparations with various combinations of antibodies against tyr-tubulin, acetylated alpha-tubulin (Ac-tubulin) or beta-tubulin, clearly revealed the composite nature of axonal MTs. Composite MTs consisted of two distinct domains, one that was relatively rich in tyr-tubulin and poor in Ac-tubulin, and the other that was relatively poor in tyr-tubulin and rich in Ac-tubulin. The transition between these domains was relatively abrupt, with the tyr-tubulin-rich domain extending from the transition to the plus-end of the MT. Quantitative analyses of fluorescence intensity along individual MTs using digital image processing revealed that the relative amount of tyr-tubulin increased by approximately 800% across the transition, whereas the relative amount of Ac-tubulin decreased by approximately 60%. Within the tyr-tubulin-rich domains, the relative amount of tyr-tubulin was generally not constant, but increased from the transition to the plus-end of the MT in a nonlinear manner. We propose that the specific pattern of variation in the extent of post-translational modification along an individual MT represents a snapshot of that polymer's growth history.

Acetylation↗
PubMed1993

[Toxic cardiomyopathy due to cocaine use].

The clinical record of 5 patients are studied. They were hospitalized in Santo Tomás Hospital with history of chronic and massive intoxication with inhaled and ingested cocaine. They all had cardiomegaly: in one, of grade I; in three, of grade III. The echocardiography mode B showed global cardiomegaly with dilatation of cavities and ejection fraction of 20% or below.

Adult↗
PubMed1993

Fractures of the zygomatic complex: a case report and review.

Traumatic injuries to the midface are not nearly as common in Canada as they are in the United States, but practitioners must still be prepared for the evaluation and treatment of patients presenting with midface fractures. This case report demonstrates the experience one individual who presented with the clinical signs and symptoms of midfacial trauma. Cases of this nature can be confidently managed by an oral and maxillofacial surgeon. A review provides knowledge regarding anatomic features, classification schemes and the diagnostic and therapeutic decisions encountered with the treatment of zygomatic complex fractures. The forward projection of the zygoma causes it to be frequently injured secondarily to blunt trauma of the midface, at the expense of protecting the orbit.

Adult↗
PubMed1993

Sites of microtubule stabilization for the axon.

We have sought to determine the principal site(s) in the neuron where axonal microtubules (MTs) are stabilized. To accomplish this, we compared the proximal and distal regions of the axon and the axon shaft with regard to their content of newly stabilized MT polymer, using the following criteria. Stable polymer was identified by its resistance to nocodazole, and newly stabilized polymer was distinguished from older stable polymer by the staining of the former but not the latter for tyrosinated alpha-tubulin. Our results indicate that roughly 36.4%, 5.4%, and 2.4% of the total MT mass in the proximal and distal regions of the axon and the axon shaft is newly stabilized, respectively. Thus, while MT stabilization occurs throughout the axon, the proximal region is by far the most active with regard to this process.

Animals↗