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Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 55 records · Page 3Linked to original sources
PubMed2003

Protein kinase C expression in salivary gland acinar epithelial cells in non-obese diabetic mice, an experimental model for Sjögren's syndrome.

We planned to investigate the expression of protein kinase C (PKC) isoforms in acinar epithelial cells of salivary glands in the non-obese diabetic (NOD) mouse to find out if they develop changes of the PKC system like those seen in the human counterpart, i.e. in Sjögren's syndrome. Parotid, submandibular, and sublingual glands from NOD and control BALB/c mice were stained with a panel of monoclonal antibodies directed against conventional (alpha, beta, and gamma), novel (delta, epsilon, and theta), and atypical (lambda and iota) PKC isoforms using the streptavidin/HRP method. Similarly to human labial salivary glands, acinar epithelial cells of the healthy control BALB/c mice contained two of the conventional PKC isoforms, alpha and beta. Acinar and ductal epithelial cells also contained the atypical PKC isoforms lambda and iota. PKC isoforms gamma, delta, epsilon, and theta were not found. NOD mice which displayed focal sialadenitis contained the same conventional and atypical PKC isoforms. The acinar cells in NOD mice, in contrast to the Sjögren's syndrome patients, did not lack PKC alpha or beta. On the contrary, PKC alpha and beta staining was stronger than in the control BALB/c mice. The present results demonstrate that both conventional and atypical PKC isoforms participate in the salivary epithelial cell biology and that there are mouse strain-associated and/or disease state-associated changes in their expression. The lack of PKC alpha and beta isoforms found in Sjögren's syndrome was not reproduced in NOD mice, which discloses one more difference between the human disease and its NOD mouse model.

Animals↗
PubMed2003

0.85-PW, 33-fs Ti:sapphire laser.

We have successfully produced a laser pulse with a peak power of 0.85 PW for a pulse duration of 33 fs in a four-stage Ti:sapphire amplifier chain based on chirped-pulse amplification. To our knowledge this result represents the highest peak power pulses yet produced in any Ti:sapphire chirped-pulse amplification system.

Journal Article↗
PubMed2003

Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells.

The prostate gland of humans and other animals accumulates a level of zinc that is 3-10 times greater than that found in other tissues. Associated with this ability to accumulate zinc is a rapid zinc uptake process in human prostate cells, which we previously identified as the hZIP1 zinc transporter. We now provide additional evidence that hZIP1 is an important operational transporter that allows for the transport and accumulation of zinc. The studies reveal that hZIP1 (SLC39A1) but not hZIP2 (SLC39A2) is expressed in the zinc-accumulating human prostate cell lines, LNCaP and PC-3. Transfected PC-3 cells that overexpress hZIP1 exhibit increased uptake and accumulation of zinc. The V(max) for zinc uptake was increased with no change in K(m). Along with the increased intracellular accumulation of zinc, the overexpression of hZIP1 also results in the inhibition of growth of PC-3 cells. Down-regulation of hZIP1 by treatment of PC-3 cells with hZIP1 antisense oligonucleotide resulted in a decreased zinc uptake. Uptake of zinc from zinc chelated with citrate was as rapid as from free zinc ions; however, the cells did not take up zinc chelated with EDTA. The cellular uptake of zinc is not dependent upon an available pool of free Zn(2+) ions. Instead, the mechanism of transport appears to involve the transport of zinc from low molecular weight ligands that exist in circulation as relatively loosely bound complexes with zinc.

Carrier Proteins↗
PubMed2003

Physiological regulation and NO-dependent inhibition of migrating myoelectric complex in the rat small bowel by OXA.

Orexin A (OXA)-positive neurons are found in the lateral hypothalamic area and the enteric nervous system. The aim of this study was to investigate the mechanism of OXA action on small bowel motility. Electrodes were implanted in the serosa of the rat small intestine for recordings of myoelectric activity during infusion of saline or OXA in naive rats, vagotomized rats, rats pretreated with guanethidine (3 mg/kg) or N(omega)-nitro-L-arginine (L-NNA; 1 mg/kg). Naive rats were given a bolus of the orexin receptor-1 (OX1R) antagonist (SB-334867-A; 10 mg/kg), and the effect of both OXA and SB-334867-A on fasting motility was studied. Double-label immunocytochemistry with primary antibodies against OXA, neuronal nitric oxide synthase (nNOS), and OX1R was performed. OXA induced a dose-dependent prolongation of the cycle length of the migrating myoelectric complex (MMC) and, in the higher doses, replaced the activity fronts with an irregular spiking pattern. Vagotomy or pretreatment with guanethidine failed to prevent the response to OXA. The OXA-induced effect on the MMC cycle length was completely inhibited by pretreatment with L-NNA (P < 0.05), as did SB-334867-A. The OX1R antagonist shortened the MMC cycle length from 14.1 (12.0-23.5) to 11.0 (9.5-14.7) min (P < 0.05) during control and treatment periods, respectively. Colocalization of OXA and nNOS was observed in myenteric neurons of the duodenum and nerve fibers in the circular muscle. Our results indicate that OXA inhibition of the MMC involves the OX1R and that activation of a L-arginine/NO pathway possibly originating from OX1R/nNOS-containing neurons in the myenteric plexus may mediate this effect. Endogenous OXA may have a physiological role in regulating the MMC.

Animals↗
PubMed2003

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer.

The objective of this phase II and pharmacologic study was to explore the feasibility, toxicity and activity of adaptive intrapatient dose escalation of cisplatin in a dose-intensive weekly schedule using predefined levels of exposure, with the ultimate aim to improve the antitumour activity of the therapy in patients with nonsmall cell lung cancer (NSCLC). Platinum DNA-adduct levels in peripheral white blood cells during treatment were used as the primary parameter for adaptive dosing. If DNA-adduct levels were not available, the area under the concentration-time curve (AUC) of unbound platinum in plasma was used for dose adaptation. Target levels for DNA-adducts and AUC have been defined in a previously performed pharmacologic study. The feasibility of adaptive dosing was tested in 76 patients with stage IIIB and IV NSCLC, who were planned to receive 6 weekly courses of cisplatin at a starting dose of 70 mg m(-2), together with daily low oral dose of 50 mg VP16. In total, 37 patients (49%) who were given more than one course received a dose increase varying from 10 to 55%. The majority of patients reached the defined target levels by a dose increase during course two. Relevant grade 2 neurotoxicity was observed in eight (10%) patients and reversible ototoxicity grade 2 in 14 (18%) patients. The strategy of adaptive intrapatient dose adjustment of cisplatin is practically feasible in a research setting even when results for dose adaptation have to be reported within a short time-period of 1 week. The toxicity appeared to be manageable in this cohort of patients. In some patients, exposure after the standard dose was substantially lower than the defined target level and significant dose escalations of more than 50% had to be applied. The response rate (RR) was relatively high: overall 40% (29 out of 72 patients) partial remission (PR), in patients with stage IIIB the RR was 60% (15 out of 25 patients) and with stage IV 30% (14 out of 47 patients). Randomised studies are needed to determine whether the adaptive dosing strategy results in better efficacy than standard dosing.

Administration, Oral↗
PubMed2003

The missing link between thermodynamics and structure in F1-ATPase.

F(1)F(o)-ATP synthase is the enzyme responsible for most of the ATP synthesis in living systems. The catalytic domain F(1) of the F(1)F(o) complex, F(1)-ATPase, has the ability to hydrolyze ATP. A fundamental problem in the development of a detailed mechanism for this enzyme is that it has not been possible to determine experimentally the relation between the ligand binding affinities measured in solution and the different conformations of the catalytic beta subunits (beta(TP), beta(DP), beta(E)) observed in the crystal structures of the mitochondrial enzyme, MF(1). Using free energy difference simulations for the hydrolysis reaction ATP+H(2)O --> ADP+P(i) in the beta(TP) and beta(DP) sites and unisite hydrolysis data, we are able to identify beta(TP) as the "tight" (K(D) = 10(-12) M, MF(1)) binding site for ATP and beta(DP) as the "loose" site. An energy decomposition analysis demonstrates how certain residues, some of which have been shown to be important in catalysis, modulate the free energy of the hydrolysis reaction in the beta(TP) and beta(DP) sites, even though their structures are very similar. Combined with the recently published simulations of the rotation cycle of F(1)-ATPase, the present results make possible a consistent description of the binding change mechanism of F(1)-ATPase at an atomic level of detail.

Adenosine Diphosphate↗
PubMed2003

Regulation of macrophage activation.

IFN-gamma rapidly primes the macrophage via JAK1/2-STAT1 pathway so that it can subsequently undergo a slower classical type 1 activation upon exposure to T helper (Th)1 cytokines such as IFNgamma or other activators, including tumor necrosis factor and lipopolysaccharide, e.g. in intracellular killing of phagocytosed Mycobacterium tuberculosis. If instead it is driven by Th2 cytokines interleukin (IL)-4 and IL-13, it undergoes alternate type 2 activation, which enhances endocytotic antigen uptake and presentation, mast cell and eosinophil involvement and type 2 granuloma formation, e.g. in response to parasitic and extracellular pathogens. Particle-induced macrophage activation was shown to differ from classical and alternate activation, showing in DNA microarray experiments (complete linkage/ Euclidean distance metric analysis) upregulation of nonsecreted structural/signaling molecules and lack of secreted proinflammatory cyto- and chemokines. The switch-off (deactivation) of already activated macrophages is an active, controlled process in which IL-10 and corticosteroids play important roles and to which 15dPGJ2, PGA1/2 and vasoactive intestinal peptide often contribute.

Animals↗
PubMed2003

Electrophoretic deposition of porous hydroxyapatite scaffold.

Bioactive porous hydroxyapatite (HA) scaffold was fabricated using electrophoretic deposition (EPD) technique in the present work. Bulk HA scaffold was achieved by repeated deposition. The green scaffold was sintered at 1200 degrees C to 82% of the theoretical density. Scanning electron microscopy examination and mercury porosimetry measurement have shown that the porosity remains interconnected and a range of pore size from several microns to hundreds of microns was obtained. X-ray diffraction analysis was performed and confirmed that there is no HA decomposition during the sintering process. Mechanical characterization has also shown that the EPD scaffold possesses excellent properties. Cell culturing experiment was carried out and the result shows that the scaffold bioactivity is not only dependent on the interconnectivity of the pores, but also the pore size.

Biocompatible Materials↗
PubMed2003

Dynorphinergic GABA neurons are a target of both typical and atypical antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus and thalamic central medial nucleus.

Administration of typical and atypical antipsychotic drugs leads to activation of cells in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus, implicating important shared effects of these drugs. However, the exact cell types responding to antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus are unclear. We report here that, in a rat model, the results of studies using double immunofluorescence labeling with antibodies directed against markers specific to candidate cell types suggest that the cells responding to haloperidol and clozapine in all three sites are: 1) neurons, rather than astrocytes; 2) inhibitory GABA neurons, but not acetylcholinergic neurons; and 3) dynorphin-containing GABA neurons, but not M-enkephalin-containing GABA neurons. The present study provides pharmacological evidence, at the cellular level in vivo, that the shared effects of antipsychotic drugs, whether typical and atypical, is activation of dynorphinergic GABA neurons in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus. Alternative ways to modulate dynorphinergic GABA neuronal activity or its target receptors might present an important new avenue for the treatment of schizophrenia and other psychotic disorders.

Acetylcholine↗
PubMed2003

Colloidal characterization and electrophoretic deposition of hydroxyapatite on titanium substrate.

Hydroxyapatite (HA) powders were prepared by a modified chemical co-precipitation method and electrophoretically deposited onto a titanium tubular substrate. The zeta potential, electromobility and the particle size of the HA suspension was characterized at various pH values and the most stable and dispersed suspension condition was identified. Electrophoretic deposition of the HA particles on the titanium substrate was then carried out at this optimum suspension condition. Studies on deposition rate and examination on the microstructure of the sintered deposit were performed. The stoichiometry of the HA before and after sintering were also confirmed. The deposition experimental data obtained in the present work was also compared with theoretical model proposed in the literature. Lastly, the adhesion strength of the coating was also quantified using shear strength tests.

Journal Article↗
PubMed2003

High levels of extra-group paternity in a population of Australian magpies Gymnorhina tibicen: evidence from microsatellite analysis.

Breeding systems vary widely in birds, from monogamous pairs through to complex group systems where subordinates assist breeding individuals to rear young each season. The Australian magpie varies geographically both in plumage patterns and social organization. Some populations of both eastern and western plumage forms are plural breeders with group size varying from three to over 15 mature individuals. This study used variation at microsatellite loci to determine the level of extra-group paternity in a population of the western form near Perth in Western Australia. Extra-group paternity was the highest recorded for any bird species to date (82%) and indicates that few offspring within a territory are sired by the social partner of the female. In addition, the data indicated that nearly 10% of juveniles were not the genetic offspring of any female within their territory, suggesting some intraspecific brood parasitism. Taken together, these findings are remarkable considering the highly territorial nature of the species and the extent of territorial defence practised by all members of the group towards extra-group conspecifics during daylight hours.

Animals↗
PubMed2003

Assessing stages of change for fruit and vegetable intake in young adults: a combination of traditional staging algorithms and food-frequency questionnaires.

Adequate fruit and vegetable intake is strongly associated with a reduced risk for various chronic diseases. US national surveys show that 18- to-24-year-olds are not consuming enough of these foods. Theory-based nutrition interventions, e.g. stage-tailored education programs, are needed for promoting fruit and vegetable consumption in this age group. Accurate stage assignment is the basis for developing effective stage-tailored interventions. In the current study, three different methods were compared for assigning stages of change in fruit and vegetable intakes by young adults. Significant differences in food intake, decisional balance and self-efficacy were found between respondents with concordant responses to the traditional stage algorithm and the food-frequency questionnaire (FFQ) and those with discordant responses. The stage assignment method that combined the staging algorithm and FFQ identified a distinct stage, labeled 'non-reflective action', in addition to the traditional five stages of change. This stage lay between the preparation and action stages with regard to food intake and psychosocial variables. Implications of the findings were discussed for future intervention programs that attempt to promote fruit and vegetable intake.

Adult↗
PubMed2003

Salivary gland scintigraphy in Sjögren's syndrome and patients with sicca symptoms but without Sjögren's syndrome: the psychological profiles and predictors for salivary gland dysfunction.

OBJECTIVE: To characterise the psychological profiles of Sjögren's syndrome (SS) and patients with sicca symptoms but without SS; to find predictors for salivary gland function; to evaluate salivary scintigraphy as a method to differentiate between SS and patients with sicca symptoms but without SS. PATIENTS AND METHODS: Psychological tests (Medical Outcomes Study Short Form General Health Survey (SF-36), Jenkins Activity Survey, Toronto Alexithymia Scale, and Maastricht Questionnaire for vital exhaustion) were performed and assessment of the function of the salivary glands made in 26 patients with primary SS, 8 with secondary SS, and 9 with sicca symptoms but without SS. Data were analysed with BMDP new system version 1.0 statistical program. RESULTS: Psychological profiles were similar in all groups. Hb, RF, ANA, and SSA differentiated between the groups. Results of salivary scintigraphy were predicted to 51% by ANA, SSA, SSB, IgG, IgA, diagnosis, vitality, and role limitations due to emotional problems. No predictors were found for the resting salivary flow. Salivary scintigraphy was pathological in 21/26 (81%) and in 8/8 (100%) patients with secondary SS, but only in 2/9 (22%) patients with sicca symptoms without SS (p=0.002) (sensitivity 85.3%, specificity 77.8%). CONCLUSIONS: Patients with sicca symptoms but without SS have sickness behaviour similar to that of patients with SS. The results of salivary scintigraphy can be predicted by diagnosis and autoimmune findings; psychological characteristics added 20% to this predictive value. Distinction between SS and patients with sicca symptoms but without SS is difficult, but in addition to autoantibodies, salivary scintigraphy can be used for this purpose.

Antibodies, Antinuclear↗
PubMed2002

Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats.

Sulfonylureas are the most commonly used oral hypoglycemic agents. Their hypoglycemic actions are produced not only by stimulating insulin secretion but also by extrapancreatic mechanisms. Some groups have already demonstrated the extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver, fat and muscle. In this study, we showed in an in situ perfused hind limb preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone body and glucose utilization.

Animals↗