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Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 523 records · Page 29Linked to original sources
PubMed1994

Neurotrophic regulation of mouse muscle beta-amyloid protein precursor and alpha 1-antichymotrypsin as revealed by axotomy.

Kunitz-inhibitor containing forms of the beta-amyloid precursor protein (beta APP), known also as protease nexin II (PNII), and alpha 1-antichymotrypsin (alpha 1-ACT), a serpin, are important components of the serine protease and inhibitor balance in many tissues. In the nervous system, this balance may have trophic or growth factor activity at different stages of development, after injury and in disease states. In the current study, using immunocytochemistry and Western blotting with antibodies against the human homologues, we analyzed whether denervation affected the localization of beta APP and alpha 1-ACT in adult mouse muscle following axotomy. In mouse muscle, anti-human alpha 1-ACT antibody detected a 60 kD immunoreactive band and anti-human beta APP antibody a band at 92 kD in both normal and denervated extracts. beta APP was present in normal mouse muscle at both neuromuscular junctions and within intramuscular nerves. alpha 1-ACT was also detected at neuromuscular junctions, on the perineurium and endothelial cell surfaces. Following axotomy, both beta APP and alpha 1-ACT disappeared from intramuscular nerves simultaneously. However, at the neuromuscular junction, alpha 1-ACT decreased more rapidly with beta APP lingering before disappearing. Since both alpha 1-ACT as well as beta APP are present within senile plaques in Alzheimer's disease brains such experiments with the nicotinic, cholinergic neuromuscular synapse in denervated muscle may help to focus experiments on the mechanism of synapse loss as well as plaque deposition in this disease.

Amyloid beta-Protein Precursor↗
PubMed1994

Insulin-like growth factor binding protein-1 at mouse neuromuscular synapses.

The insulin-like growth factor (IGF) signaling system includes the growth factors and their cell surface receptors, along with circulating IGF binding proteins (IGFBPs) that may alter and modulate the action of these neurotrophic hormones. These IGFBPs, along with IGFs and receptors, have been detected in various tissues including the brain. In this study, using polyclonal antibody to human IGFBP-1 or bovine IGFBP-2, we found that mouse muscle extracts contain similar-sized proteins that cross-react with these antibodies on Western immunoblots. After establishing that these antibodies reacted with the homologous murine IGFBPs, we performed immunocytochemistry to demonstrate the localization of IGFBP-1 at the neuromuscular junction, a model nicotinic, cholinergic synapse, as well as within intramuscular nerves. IGFBP-2, a distinct macromolecule, is present on the surface of muscle fibers and is not present within synapses or nerves.

Animals↗
PubMed1994

Insulin-like growth factor binding protein-1 is pre-synaptic at mouse neuromuscular synapses and is transported in nerve.

In a previous study, we localized insulin-like growth factor binding protein 1 (IGFBP-1) to mouse neuromuscular junctions, and intramuscular nerves. To determine if pre-synaptic accumulation of IGFBP-1 occurred, we used double ligation of sciatic nerve in adult mice at different time points. IGFBPs were detected by Western ligand blot (WLB) with 125I-IGF-I. WLB and Western immunoblot (WIB) analysis of extracts from double-ligated nerves showed a delayed (6 days) increase of IGFBP-1 in the soluble fraction between the ligatures and distal to the distal ligature. For comparison we evaluated transport of neurofilament components, using WIB and confirmed the primarily anterograde transport of these intraaxonal proteins. These data suggest that expression of IGFBP-1 is both by activated Schwann cells as well as retrograde axonal transport with likely entry into the axon at the synapse.

Animals↗
PubMed1994

Plasma phospholipid fatty acid composition and factor VII coagulant activity.

Plasma phospholipid fatty acid composition reflects, to a moderate degree, the fatty acid composition of the diet. To determine whether plasma phospholipid fatty acid composition might influence factor VII coagulant activity (factor VIIc), we examined 2207 middle-aged adults free of diabetes and cardiovascular disease. Factor VIIc was associated positively with the percentage of fatty acids that was saturated, and it was associated negatively with the linoleic acid percentage and the phospholipid polyunsaturated/saturated fatty acid ratio. For example, a 1.9% greater saturated fatty acid level was associated with approximately a 5% higher factor VIIc. These results suggest a role for dietary fat composition, or related dietary patterns, in determining levels of factor VIIc.

Age Factors↗
PubMed1994

Impact of the saponin adjuvant QS-21 and aluminium hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi.

The impact of the adjuvants QS-21 and aluminium hydroxide (alum) on the immunogenicity of recombinant outer surface proteins A (OspA) and B (OspB) of Borrelia burgdorferi was investigated. Both non-acylated OspA and OspB derived from strain B31 were expressed in Escherichia coli and purified by reversible citraconylation and anion-exchange chromatography. Antisera to OspA or OspB were prepared in mice with antigens formulated with QS-21 or alum, and evaluated for specific immunoglobulin G isotypes, agglutination and borreliacidal activity. QS-21 significantly enhanced IgG2a and IgG2b antibody responses to OspA and OspB, and IgG1 response to OspA when compared with the formulation containing antigen alone. In contrast, alum significantly inhibited the induction of IgG2a and IgG2b responses to OspA. Alum had no significant effect on IgG1 response to OspA, or IgG2a and IgG2b responses to OspB, but significantly enhanced IgG1 antibody response to OspB. Antisera to OspA or OspB formulated by QS-21 possessed higher titres of agglutinating antibody than antisera to OspA or OspB alone. Borreliacidal activity was eight- to 64-fold higher in antisera to OspA formulated with QS-21 than in antisera to OspA formulated with or without alum. These antisera were highly borreliacidal to New York strain B31, a California isolate CA-2-87, German isolate Fr, and Swedish isolate G25. Antisera to OspB formulated with QS-21 were highly borreliacidal to strains B31 and Fr, but not to CA-2-87 and G25. Antisera to OspB formulated with alum were borreliacidal only to B31. Thus, OspA was superior to OspB and QS-21 superior to alum at eliciting functional antibody responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Hypothalamic stimulation induces vagally mediated hypocalcemia in the rat.

To elucidate hypothalamic involvement in blood calcium homeostasis, the effects of unilateral electrical stimulation (0.1 mA, 0.5 ms, 30 Hz, 60 min) of the lateral hypothalamic area (LHA), the paraventricular nucleus (PVN), and the ventromedial nucleus of the hypothalamus (VMH) on the blood concentration of ionized calcium were examined in the anesthetized rats. LHA stimulation induced a sustained decrease (0.05-0.07 mM fall) in the blood calcium level during the period of 60 to 150 min (end of the measurements) after stimulation. In contrast, PVN stimulation elicited a transient hypocalcemia (0.07 mM decrease) 60 min after stimulation. The hypocalcemic effects of LHA and PVN stimulation were eliminated by vagotomy of the gastric branches and the thyroid/parathyroid branches, respectively. VMH stimulation, using the same parameters, did not induce any significant change in blood calcium. The results suggest that the LHA and the PVN have a hypocalcemic function that is mediated, at least in part, by the vagus nerve innervating the stomach and the thyroid/parathyroid glands, respectively.

Anesthesia↗
PubMed1994

Ventromedial hypothalamus mediates stress-induced hypocalcemia via the gastric vagus in rats.

A hypothalamo-vagal mechanism of immobilization (IMB) stress-induced hypocalcemia was investigated in rats. Bilateral lesions in the ventromedial nucleus of the hypothalamus (VMH), but not those of the lateral hypothalamic area (LHA) or the paraventricular nucleus (PVN), eliminated the calcium-lowering effect of IMB. None of these lesions, however, affected the basal levels of the blood calcium. An electrical stimulation of the VMH induced a significant decrease in the blood calcium level (0.07 mM fall) 60 min after stimulation. The hypocalcemic response was eliminated by a vagotomy of the gastric branches but not by that of the thyroid/parathyroid branches. These results suggest that the VMH mediates IMB-induced hypocalcemia through its influence on the gastric vagus.

Animals↗
PubMed1994

Highly cooperative and hysteretic response of the skeletal muscle ryanodine receptor to changes in proton concentrations.

Ryanodine receptors are key molecules in excitation-contraction coupling of skeletal muscle. They form the pore of the calcium release channel, which is regulated by Ca and ATP. Multiple proton titration sites are involved in controlling the different open states of the channel, as indicated by the following: i) the channel had a biphasic response to changes in proton concentrations around neutral pH; ii) the activities of the channel were inhibited by acidic pHs in a highly cooperative manner; and iii) the channel exhibited pronounced hysteresis to changes in pH. Four distinct conductance states can be identified in the single ryanodine-activated calcium release channel. The distribution of the multiple conductance states depends on the level of [Ca], ATP, and pH in the recording solution. The data are consistent with the multimeric structure of the skeletal muscle ryanodine receptor.

Adenosine Triphosphate↗
PubMed1994

Pharmacokinetic-dynamic relationship of cisplatin in vitro: simulation of an i.v. bolus and 3 h and 20 h infusion.

The profiles of an i.v. bolus and 3 h and 20 h infusion of cisplatin (CDDP) were simulated in vitro by using a culture of the IGROV1 human ovarian cancer cell line. Disappearance of pharmacologically active unbound CDDP was accomplished by adding human albumin to the medium. Total and unbound CDDP and CDDP-DNA adduct levels were quantitated by atomic absorption spectroscopy (AAS), and tumour cell survival was measured by the clonogenic assay. The design of the experiment resulted in non-significant differences in the magnitude of the area under the concentration-time curve (AUC) of unbound CDDP between the three dose-input functions (AUC i.v. bolus, 6.34 +/- 0.36; 3 h infusion, 6.35 +/- 0.59; and 20 h infusion, 6.76 +/- 0.40 micrograms h ml-1). Also, the differences between the area under the CDDP-DNA adduct-time curves (AUA) of the three dose-input functions were not significant. The initial rate of decline of the CDDP-DNA adduct-time curve was significantly higher for the i.v. bolus and 3 h infusion than for the 20 h infusion. There was a log-linear relationship between the AUC of unbound CDDP and cell survival. These relationships were not significantly different between the three dose-input functions. Variation in the rate of input of CDDP leads to differences in the shape of the AUC and AUA without significant effects on cell survival.

Adenocarcinoma↗
PubMed1994

Trinitrophenol reactive T-cell hybridomas recognize antigens that require antigen processing.

Protein antigens must be taken up, processed, and displayed on the surface of antigen-presenting cells in association with major histocompatibility complex molecules before they can be recognized by T cells. Whether recognition of the haptens used to study allergic contact hypersensitivity in murine models similarly requires processing has not been determined. We analyzed whether presentation of trinitrophenol to trinitrophenol reactive T-cell hybridomas requires antigen processing by studying the effects of inhibitors of antigen processing and presentation on the ability of a syngeneic B-cell tumor (A20) to present trinitrophenol to a series of interleukin-2 producing, trinitrophenol specific, major histocompatibility complex class II-restricted T-cell hybridomas. The ability of trinitrophenol modified A20 cells to stimulate the hybridomas was completely inhibited by monoclonal, anti-trinitrophenol, or anti-Ia antibodies and was significantly reduced by paraformaldehyde fixation immediately after trinitrophenol modification. Trinitrophenol-modified A20 cultured at 37 degrees C for 2 h prior to fixation was significantly more effective at stimulating the hybridomas than trinitrophenol-modified A20 fixed immediately. The ability of A20 to present trinitrophenol was inhibited by chloroquine. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of trinitrophenol modified lymph node dendritic cells to stimulate the trinitrophenol specific hybridomas. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of A20 cells to present ovalbumin to ovalbumin-specific hybridomas as they had on the ability of trinitrophenol modified A20 cells to present trinitrophenol to the trinitrophenol specific hybridomas. One of seven T-cell hybridomas responded to trinitrophenol modified ovalbumin but not other trinitrophenol modified proteins. These results suggest that, at least in part, T cells in the contact hypersensitivity response to trinitrophenol recognize antigens that require processing and that trinitrophenol modified proteins can be recognized.

Albumins↗
PubMed1994

Long-term care facility policies on life-sustaining treatments and advance directives in Canada.

OBJECTIVE: To describe the prevalence and content of long-term care facility policies regarding the use of life-sustaining treatments (cardiopulmonary resuscitation (CPR), artificial hydration and nutrition, dialysis, antibiotics for life-threatening infections, transfer to acute care hospital) and advance directives in Canada. DESIGN: Cross-sectional mailed survey. SETTING: Canadian long-term care facilities with 25 beds or more listed in the 1991-92 Directory of Long Term Care Centres in Canada. Institutions listed as, "general hospitals," "psychiatric hospitals," "children's treatment centres," "group homes," or as purely residential facilities were excluded. PARTICIPANTS: Chief Executive Officers or their designates. MAIN OUTCOME MEASURES: Respondents' self-reports regarding the existence of life-sustaining treatment or advance directive policies and content analysis of the policies themselves. RESULTS: Of 1472 long-term care facilities, 1021 (69%) responded. Of these, 344 (34%) institutions had 397 policies regarding the use of life-sustaining treatments or advance directives. Three hundred twenty facilities (31%) had 349 do-not-resuscitate (DNR) policies (40% on CPR alone and 60% on CPR plus other life-sustaining treatments). Seventeen institutions (2%) each had one policy addressing life-sustaining treatments other than CPR, and 31 institutions (3%) each had one policy addressing advance directives. Of the 397 policies, 171 (43%) required routine discussion with all patients, 156 (39%) mentioned futility, 331 (83%) indicated that the competent patient had the right to make a decision about life-sustaining treatment, 265 (67%) indicated that the family of the incompetent patient had this right, 27 policies (7%) mentioned conflict resolution, 378 (95%) had an explicit requirement for recording the decision, 10 (3%) required explicit communication of the decision to the competent patient, 10 (3%) required such communication to the family of the incompetent patient, 260 (66%) required updating of the decision, and 213 (54%) mentioned rescinding or changing the decision. CONCLUSIONS: Only one-third of Canadian long-term care facilities have do-not-resuscitate policies, and even fewer have policies on advance directives or life-sustaining treatments other than CPR. The policies themselves could be improved by encouraging routine advance discussions, scrutinizing the use of the futility standard, stipulating procedures for conflict resolution, and explicitly requiring communication of the decision to competent patients or substitute decision makers of incompetent patients.

Advance Directives↗
PubMed1994

Linkage of stress-induced hypocalcemia, gastric lesions, and emotional behavior in Wistar-Kyoto rats.

The effects of water-restraint stress on blood calcium levels and gastric pathology and their behavioral relevance were examined in Wistar-Kyoto (WKY) and Wistar rats. The stress induced more severe hypocalcemia (0.32 mM decrease) and gastric lesions (34.6 mm in mean length) in WKY rats than in Wistar rats (0.19 mM and 17.7 mm, respectively). The magnitude of hypocalcemia correlated positively with that of gastric lesions in both strains (WKY, r = 0.59; Wistar, r = 0.69). In the forced-swimming test, WKY rats exhibited a longer immobility time (6.53 min) and a shorter struggling time (0.54 min) than Wistar rats (3.33 and 1.90 min, respectively). The severity of hypocalcemia and gastric lesions correlated positively (r = 0.59 and 0.69, respectively) with the length of immobility time in the WKY rats, while it correlated negatively (r = -0.70 and -0.61, respectively) with the length of struggling time in the Wistar rats. These results suggest that stress-induced hypocalcemia and gastric lesions are closely related and are also influenced by behavioral responsiveness in a strain-dependent manner.

Animals↗
PubMed1994

Hypothalamic linkage in stress-induced hypocalcemia, gastric damage, and emotional behavior in rats.

The effects of hypothalamic lesions on stress-induced hypocalcemia, gastric damage, and swim test-evoked behavior were examined in rats. Bilateral lesions of the ventromedial nucleus in the hypothalamus (VMH) eliminated water-restraint stress-induced hypocalcemia and attenuated any gastric damage compared with those in the sham-operated rats. In contrast, lesions in the paraventricular nucleus (PVN) exacerbated both the stress-induced hypocalcemia and gastric lesions in comparison with those in the control rats. In a forced-swimming test, the VMH-lesioned rats showed a significantly shorter time of immobility as well as a longer duration of struggling than the control rats, respectively, while the PVN-lesioned animals spent a longer time in immobility and a shorter period struggling than the control rats. These results suggest that the VMH has an accelerative action in stress-induced hypocalcemia, gastric lesions, and behavioral despair, while the PVN has an opposite effect.

Animals↗
PubMed1994

Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND AND PURPOSE: We tested the hypothesis that body mass, waist-to-hip circumference ratio, physical inactivity, diabetes, hyperglycemia, and fasting insulin are each positively associated with asymptomatic carotid artery wall thickness. METHODS: Average intimal-medial carotid wall thickness (an indicator of atherosclerosis) was measured noninvasively by B-mode ultrasonography in cross-sectional samples of 45- to 64-year-old adults, both blacks and whites, free of symptomatic cardiovascular disease, in four US communities. RESULTS: Sample mean carotid wall thickness was approximately 0.7 mm in women (n = 7956) and 0.8 mm in men (n = 6474). Body mass, waist-to-hip ratio, work physical activity, diabetes, and fasting insulin were associated (P < .05) with carotid wall thickness in the hypothesized direction. Adjusted for age, race, smoking, body mass index, artery depth, and Atherosclerosis Risk in Communities field center, mean wall thickness was greater by 0.02 mm in women and 0.03 mm in men for a 0.07-unit (one SD) larger waist-to-hip ratio. Adjusted mean wall thickness was about 0.07 mm thicker in participants with diabetes mellitus and 0.02 mm thicker in participants with hyperglycemia (fasting glucose 6.4 to 7.7 mmol/L) than in subjects with fasting glucose < 6.4 mmol/L. Adjusted mean wall thickness increased by about 0.02 mm with an increase of 100 mmol/L in fasting serum insulin. CONCLUSIONS: Abdominal adiposity, physical inactivity, and abnormal glucose metabolism are associated positively with carotid intimal-medial wall thickness, suggesting these factors contribute to atherogenesis.

Aging↗
PubMed1994

In situ ischemia and hypoxia enhance alveolar macrophage tissue factor expression.

Alveolar and interstitial fibrin deposition is a prominent pathologic feature in many acute lung injury syndromes. Previous studies have suggested that ischemic lung preservation has a stimulatory effect on donor alveolar macrophages (Mphis) during transplantation. An animal model of lung preservation was developed to examine the hypothesis that ischemia enhances Mphi procoagulant activity (PCA) as a potential mechanism contributing to lung reperfusion injury. Histologic examination of ischemic lungs reperfused ex vivo revealed evidence of alveolar fibrin deposition. Mphis lavaged from lungs stored for at least 8 h at 21 degrees C exhibited increased PCA. The use of factor-deficient human plasma characterized this Mphi procoagulant as tissue factor (TF). Since increased PCA correlated with decreased airspace pO2 at the end of preservation, the effect of various O2 concentrations on PCA induction in vivo and in vitro was examined. Lung inflation during ischemia with decreasing O2 concentrations confirmed that hypoxia was associated with a rise in Mphi PCA in situ. However, in vitro exposure of Mphis to hypoxia did not increase Mphi PCA, suggesting that hypoxia alone was not responsible for induction of this procoagulant effect. Northern blot analysis demonstrated an increase in TF mRNA levels from in situ but not in vitro Mphis, thereby confirming transcriptional TF induction in this group. In addition, enhanced PCA was observed when Mphis were suspended in the bronchoalveolar lavage supernatant from the ischemic lungs stored at 21 degrees C. This suggests that in situ lung ischemia and hypoxia may produce soluble factors that either directly or indirectly stimulate Mphi TF expression. These factors may contribute to Mphi-mediated ischemic lung injury.

Animals↗
PubMed1994

Fisher's method of scoring in statistical image reconstruction: comparison of Jacobi and Gauss-Seidel iterative schemes.

Many algorithms for medical image reconstruction adopt versions of the expectation-maximization (EM) algorithm. In this approach, parameter estimates are obtained which maximize a complete data likelihood or penalized likelihood, in each iteration. Implicitly (and sometimes explicitly) penalized algorithms require smoothing of the current reconstruction in the image domain as part of their iteration scheme. In this paper, we discuss alternatives to EM which adapt Fisher's method of scoring (FS) and other methods for direct maximization of the incomplete data likelihood. Jacobi and Gauss-Seidel methods for non-linear optimization provide efficient algorithms applying FS in tomography. One approach uses smoothed projection data in its iterations. We investigate the convergence of Jacobi and Gauss-Seidel algorithms with clinical tomographic projection data.

Algorithms↗