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Biomedical subjects

A K Hall

Publications and source records attributed to A K Hall.

At least 55 records · Page 3Linked to original sources
PubMed1990

Regulation of calbindin-D28K gene expression by 1,25-dihydroxyvitamin D3 in chick kidney.

We report here the use of a cloned cDNA for the avian calbindin-D28K (28 kD, vitamin D-dependent calcium binding protein, CaBP) to investigate the expression of the chick calbindin gene in the kidney. All three cal-bindin-D28K mRNA species (2000, 2600, and 3100 nucleotide transcripts) were present in the kidney tissue of chronically vitamin D-deficient (-D) chicks; this basal constitutive level of expression was, however, enhanced by administration of the vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in both a time- and dose-dependent manner. D-deficient chick renal calbindin-D28K protein levels (measured by ELISA) were maximally (twofold) stimulated by 6.5 nmole per animal of 1,25-(OH)2D3 when measured 48 h later; a concomitant level of augmentation of calbindin-D28K mRNA accumulation was also observed at this time. Time course experiments showed that enhanced renal calbindin-D28K mRNA accumulation (in -D chicks) was significantly stimulated as early as 8 h and were maximal 12 h after a single pharmacologic dose of 1,25-(OH)2D3; this elevated level of gene expression was maintained for at least 72 h. Renal calbindin-D28K protein levels (constitutively expressed in the -D chick) were significantly stimulated (twofold) as early as 12 h following the single dose of steroid hormone; the level of calbindin-D28K also remained elevated for a minimum of 72 h. Collectively, these data indicate that 1,25-(OH)2D3 acts upon the renal calbindin-D28K gene in a manner similar to that operable in the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Regulation of calbindin-D28K gene expression in the chick intestine: effects of serum calcium status and 1,25-dihydroxyvitamin D3.

Calbindin-D28K is a member of a superfamily of calcium binding proteins that share a common avidity for the divalent calcium ion. The ambient concentration of calcium in the blood circulation is thought to orchestrate the release of parathyroid hormone and calcitonin and to govern the activity of renal 1-hydroxylase and thereby synthesis of 1,25-dihydroxyvitamin D3. We report here the results of experiments designed to assess the possible contribution of dietary calcium status upon calbindin-D28K gene expression in the intestine of vitamin D-deficient chicks. The actions of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and dietary calcium intake upon intestinal calbindin-D28K and calbindin-D28K mRNA were monitored by ELISA and dot-blot hybridization analyses, respectively. Vitamin D3-deficient chicks were fed either a calcium-supplemented diet (3% w/w) or a diet containing low calcium (0.4% w/w). These dietary manipulations evoked a highly significant change in serum calcium status. However, the levels of calbindin-D28K protein and its corresponding mRNA were unaffected. Administration of 1,25-(OH)2D3 (1-16 nmol per animal) to both "normocalcemic" and hypocalcemic vitamin D-deficient chicks resulted in an equivalent stimulation of duodenal calbindin-D28K accumulation of calbindin-D28K mRNA. Intestinal calbindin-D28K was stimulated 20- to 28-fold (above control levels) by 6-8 nmol 1,25-(OH)2D3 in both dietary treatment groups when measured 48 h after the single injection. Hence, despite the existence of a relatively large difference in serum calcium levels, the molecular actions of 1,25-(OH)2D3 in the vitamin D-deficient animal are apparently well insulated from serum calcium chemistry. These observations support the notion that, in the absence of vitamin D3, the calcium ion per se is unable to modulate the calbindin-D28K gene in vivo.

Animals↗
PubMed1990

Thymosin beta 10 levels in developing human brain and its regulation by retinoic acid in the HTB-10 neuroblastoma.

Human fetal brain expresses high levels of a polypeptide identified by protein biochemistry and molecular cloning as thymosin beta 10. Within the first 18 months after birth, the thymosin beta 10 content of human brain falls to undetectable levels. In order to establish the molecular basis of this process we screened a number of human tumor cell lines derived from the nervous system for the presence of thymosin beta 10. All of the cell line expressed authentic thymosin beta 10. However, in the HTB-10 neuroblastoma, retinoic acid caused a reduction in the level of thymosin beta 10. This effect of the retinoid was conditional upon its continual presence in the tissue culture medium and was not evident in the other cell lines examined. These results suggest that the thymosin beta 10 gene may be a target for retinoids in the developing nervous system.

Amino Acid Sequence↗
PubMed1990

Binding properties of detergent-solubilized NCAM.

An assay has been designed for the identification of NCAM-binding proteins present in an NP-40 detergent extract of brain membranes. This method, which is capable of analyzing both heterophilic and homophilic interactions, uses species-specific antibodies against NCAM in combination with radioiodination, so that after unlabeled chicken and iodinated frog brain membrane proteins were allowed to interact, the chicken NCAM could be specifically isolated by immunoaffinity adsorption. The radiolabeled frog proteins coisolated with chicken NCAM were then characterized by one- and two-dimensional gel electrophoresis in combination with immunoblotting. The only detectable NCAM-binding proteins were identified as the 140- and 180-kD forms of NCAM. The presence and absence of polysialic acid on NCAM did not change the amount or nature of the frog proteins immunopurified under these conditions. As an alternative for detecting heterophilic ligands, a simplified immunoprecipitation method was employed using either iodine or sulfate radiolabels. Again under these conditions only NCAM was detected. These results are consistent with the hypothesis that the major binding protein for NCAM is NCAM itself, and suggest that differences in polysialic acid content do not directly alter the properties of NCAM's homophilic binding site.

Animals↗
PubMed1989

Physical illness encountered in patients with eating disorders.

Careful evaluation for medical illness with a severity rating scale of 276 eating-disorder patients admitted to hospital revealed that patients with anorexia and bulimia were at risk for developing medical complications. Severe cardiovascular complications were most likely to occur in eating-disorder patients who were also diuretic and/or laxative abusers. Forty percent of patients with bulimia had significant medical complications. The findings suggest that a medical work-up should be carefully undertaken in both anorexic and bulimic patients admitted to hospital. A mixed history of severe anorexia nervosa alternating with periods of bulimia was most likely to lead to severe life-threatening illness. Seventy percent of the bulimic patients admitted required some medical treatment. Five percent were considered severely medically ill, while 34% suffered from a significant medical disorder. Ten percent of patients with restrictive anorexia or anorexia alternating with binge/purge required intensive care unit (ICU) placement. Most illnesses requiring medical treatment were unknown to the patient and the patient's physician at the time of admission.

Anorexia Nervosa↗
PubMed1989

Sexual abuse in patients with anorexia nervosa and bulimia.

Few studies have documented the extent and nature of sexual abuse among women who later come to treatment for anorexia nervosa or bulimia. This comparison study reports on a sample of 158 patients admitted to an eating-disorder unit, of whom 60 gave a history of sexual abuse, compared to 98 with no history of abuse. Fifty percent of the anorexic and bulimic patients had suffered sexual abuse, compared to only 28% of patients admitted with other eating-disorder diagnoses; this was a significant difference (p less than 0.001). Of the four types of abuse surveyed, only those patients suffering rape were likely to have sought help from caregivers prior to admission (p less than 0.001). The authors report on likely perpetrators of abuse, age of first abuse, and frequency of depressive symptoms in the abused population. The data from this study strongly suggest that the possibility of sexual assault or abuse must be assessed and the results included in a comprehensive therapy plan for eating-disorder patients.

Adolescent↗
PubMed1989

Facilitation by tachykinins of neurotransmission in guinea-pig pulmonary parasympathetic nerves.

1. The effect of tachykinins on cholinergic neurotransmission was studied in an innervated tracheal tube preparation isolated from guinea-pigs anaesthetized with urethane. The tracheal tube was bathed in Krebs-Henseleit solution containing 5 microM indomethacin. 2. Neurokinin A (NKA), eledoisin (El) and substance P (SP) caused concentration-dependent increases in intraluminal pressure (ILP), with an order of potency NKA greater than El much greater than SP. 3. Low concentrations of tachykinins, that had little effect on ILP, caused an increase in the contractions elicited by stimulation of the preganglionic vagal nerve fibres and by postganglionic (transmural) stimulation. The order of potency was NKA greater than or equal to El greater than SP. Contractions induced by exogenous acetylcholine (ACh) were not increased by the tachykinins. 4. The magnitude of the tachykinin-induced augmentation of responses to nerve stimulation was inversely related to stimulation voltage and frequency. 5. These results suggest that tachykinins act on NK2 receptors, both on the trachealis muscle and on postganglionic pulmonary parasympathetic nerve terminals. Activation of the neuronal receptors may increase the probability of transmitter release from the nerve terminals.

Animals↗
PubMed1989

Mitral valve prolapse and anxiety disorders in patients with anorexia nervosa.

Much has been written about the occurrence of mitral valve prolapse among eating disordered patients. Despite this literature, a causal relationship between the two conditions has yet to be established. The present study evaluated 500 patients with eating disorders and demonstrated an association between a low median ideal body weight and the frequency of mitral valve prolapse (P less than 0.001). The physical signs and symptoms of mitral valve prolapse disappeared in eating disordered patients with the return of normal weight (P less than 0.001). Contrary to prior reports, there was no association between mitral valve prolapse and the occurrence of diagnosable panic or anxiety disorders. The results of this study suggest that the symptoms of anxiety and panic associated with mitral valve prolapse in eating disordered individuals may be due to physiologic change in cardiac status related to weight rather than central nervous system changes associated with classic anxiety disorders.

Adolescent↗
PubMed1989

Sexual abuse in patients with eating disorders.

The incidence of sexual abuse in eating disorder patients appears significant. Fifty percent of both our anorectic and bulimic patients reported a history of sexual abuse while only 28% of a non-anorexic, non-bulimic control population reported similar problems (p less than 0.01). Several patterns of behavior seemed related to previous sexual assault. In one, the eating disorder was used to change the body image of the patient and therefore to provide a defense to future abuse. Other behaviors which occurred more specifically in bulimic women dealt with a projection of repressed anger toward male authority figures. Forty six percent of the bulimic women seen in our study exhibited some promiscuous behavior, using sex either as a gauge of their own self worth or as a means of punishing men. It is essential that sexual issues be addressed early in the treatment of patients with eating disorders. Disclosure is often difficult particularly in outpatient situations where the patient lives at home with her family. It usually does not occur in such cases until the later stages of therapy, or until the patient is hospitalized. Rape is the exception since our data suggests that it is usually revealed early in the course of treatment (p less than 0.001). Once disclosure occurs, a dramatic change is usually seen in the patient and treatment becomes more effective. As the patient deals with the issues of sexual abuse, they no longer need to deny their sexuality or punish themselves or others. Issues of guilt, depression, repressed anger, low self-esteem, social isolation and inadequacy are important and need to be addressed during the course of therapy with sexually abused patients.

Adolescent↗
PubMed1988

The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions.

The neural cell adhesion molecule (NCAM) can influence a number of diverse intercellular events, including junctional communication, the association of axons with pathways and targets, and signals that alter levels of neurotransmitter enzymes. These pleiotropic effects appear to reflect the ability of NCAM to regulate membrane-membrane contact required to initiate specific interactions between other molecules. Such regulation can occur through changes in either NCAM expression or the molecule's content of polysialic acid (PSA). When NCAM with a low PSA content is expressed, adhesion is increased and contact-dependent events are triggered. In contrast, the large excluded volume of NCAM PSA can inhibit cell-cell interactions through hindrance of overall membrane apposition.

Animals↗
PubMed1988

Differential effects of 1,25-dihydroxyvitamin D3 upon intestinal vitamin D3-dependent calbindin (a 28,000-dalton calcium binding protein) and its mRNA in D-replete and D-deficient chickens.

The effect of vitamin D3 status upon the responsiveness of chick intestinal epithelium to exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was studied. Intestinal calbindin [A recent consensus decision was made to redesignate the vitamin D-dependent calcium binding protein as "calbindin-D28K" (R.H. Wasserman (1985) in Vitamin D: Chemical, Biochemical, and Clinical Update (Norman, A.W., Schaefer, K., Grigoleit, H.-G., and Herrath, D.V., Eds.), pp. 321-322, de Gruyter, Berlin/New York).] protein and intestinal calbindin mRNA were quantitated in birds which had been raised on a vitamin D3-deplete (-D) or on a vitamin D3-replete (+D) diet. 1,25(OH)2D3 stimulated intestinal calbindin mRNA levels in -D chickens in a proportional dose-dependent manner, when measured at both 12 and 48 h after administration of the hormone. A first increase was observed with 1,25(OH)2D3 concentrations between 0.065 and 0.65 nmol. The maximal stimulation achieved by 1,25(OH)2D3 (6.5-18 nmol) in -D tissue was approximately 10-fold over the calbindin mRNA levels present in vehicle-treated birds. The increase of calbindin mRNA in -D birds was associated with a similar dose-dependent increase in calbindin protein in 1,25(OH)2D3-treated -D birds after 12 or 48 h. In +D intestine, while exogenous 1,25(OH)2D3 also increased calbindin mRNA levels in a dose-dependent fashion, the maximal stimulation observed after 5 h (1.2- to 2-fold) was clearly less than that observed in -D intestine. In contrast to -D birds, intestinal calbindin levels in +D birds were decreased by administration of exogenous 1,25(OH)2D3. Administration of 32.5 to 65 nmol 1,25(OH)2D3 resulted in an approximately 1.8-fold repression compared to vehicle-treated birds. This differential responsiveness between +D and -D intestines with respect to 1,25(OH)2D3 was not explained either by differences in the uptake in the chromatin fractions of these tissues or by metabolism of radiolabeled 1,25(OH)2D3. Dietary withdrawal of vitamin D3 led to a gradual decline in ambient intestinal calbindin levels, while intestinal sensitivity to 1,25(OH)2D3 was restored. These findings suggest that vitamin D3 status regulates intestinal responsiveness to the seco-steroid 1,25(OH)2D3.

Animals↗
PubMed1988

The organization of cytoplasm at the presynaptic active zone of a central nervous system synapse.

The axoplasm at the presynaptic active zone of excitatory synapses between parallel fibers and Purkinje cell spines contains a meshwork of distinct filaments intermingled with synaptic vesicles, seen most clearly after the rapid freezing, freeze-etch technique of tissue preparation. One set of filaments extends radially from synaptic vesicles and intersects similar filaments associated with vesicles as well as larger filaments arising from the presynaptic membrane. The small, vesicle-associated filaments appear to link synaptic vesicles to one another and to enmesh them in the vicinity of the synaptic junction. The vesicle-associated filaments could be synapsin I because they have the same molecular dimensions and are distributed in the same pattern as synapsin I immunoreactivity.

Animals↗