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PubMed2003

The pollination of Trimenia moorei (Trimeniaceae): floral volatiles, insect/wind pollen vectors and stigmatic self-incompatibility in a basal angiosperm.

Trimenia moorei (Oliv.) Philipson is an andromonoecious liane with >0.40 of the total flower buds maturing as bisexual flowers. Male and bisexual flowers are strongly scented with pollen, anther sacs and receptacle scars testing positively for volatile emissions. Scent analyses detect over 20 components. The major fatty acid derivative is 8-heptadecene, and 2-phenylethanol dominates the benzenoids. While hover-flies in the genera Melangyna and Triglyphus contact the stigma with their probosces, the stigma secretes no free-flowing, edible fluids. Copious pollen is the only edible reward consumed by hover-flies (Syprhidae), sawflies (Pergidae) and bees in the families Apidae, Colletidae and Halictidae. All these insects carried pollen of T. moorei on their heads, legs and thoraces and female bees in the genera Apis, Exoneura, Leioproctus and Lasioglossum stored pollen on their hind legs. Pollen traps also indicate that pollen is shed directly into the air, permitting wind pollination. When bisexual flower buds are bagged (isolated from insect foragers) on the liane then subjected to a series of hand-pollination experiments after perianth segments open, the structural analyses of pollen-carpel interactions indicate that T. moorei has a trichome-rich dry-type stigma with an early-acting self-incompatibility (SI) system. Bicellular pollen grains deposited on stigmas belonging to the same plant germinate but fail to penetrate intercellular spaces, while grains deposited following cross-pollination reach the ovule within 24 h. Fluorescence analyses of 76 carpels collected at random from unbagged (open-pollinated) flowers on five plants indicates that at least 64% of carpels are cross-pollinated in situ. Trimenia moorei is the first species within the ANITA group, and second within reilictual-basal angiosperm lineages, to exhibit stigmatic SI in combination with dry-type stigma and bicellular pollen, a condition once considered to be atypical for angiosperms as a whole but now known to be present in numerous taxa.

Animals↗
PubMed2003

Differential diagnosis of adrenal masses by chemical shift and dynamic gadolinium enhanced MR imaging.

Chemical shift MRI is widely used for identifying adenomas, but it is not a perfect method. We determined whether combined dynamic MRI methods can lead to improved diagnostic accuracy. Fifty-seven adrenal masses were examined by chemical shift and dynamic MR imaging using 2 MR systems. The masses included 38 adenomas and 19 non-adenomas. In chemical shift MRI studies, the signal intensity index (SI) was calculated, and the lesions classified into 5 types in the dynamic MRI studies. Of the 38 adenomas studied, 37 had an SI greater than 0. In the dynamic MRI, 34 of 38 adenomas showed a benign pattern (type 1). If the SI for the adenomas in the chemical shift MRI was considered to be greater than 0, the positive predictive value was 0.9, and the negative predictive value was 0.94 and kappa = 0.79. If type 1 was considered to indicate adenomas in the dynamic MRI, the corresponding values were 0.94, 0.81 and kappa = 0.77 respectively. The results obtained when the 2 methods were combined were 1, 0.95 and kappa = 0.96 respectively. The chemical shift MRI was found to be useful for identifying adenomas in most cases. If the adrenal mass had a low SI (0 < SI < 5), dynamic MRI was also found to be helpful for making a differential diagnosis.

Adenoma↗
PubMed1996

Myosin heavy chain profile of cat soleus following chronic reduced activity or inactivity.

To determine the role that normal neuromuscular activity plays in maintaining the myosin heavy chain (MHC) profile of adult cat soleus muscles, the spinal cords of 4 cats were transected (ST) and 8 cats were spinal isolated (SI) for 6 months. Nine nonoperated cats served as controls. Electrophoresis demonstrated that the soleus from control cats contained 98% type I, and 2% IIa MHCs. Both ST and SI resulted in decreased type I and increased IIa MHC, as well as de novo expression of IIb MHC. Immunohistochemistry with MHC-specific antibodies demonstrated that the soleus from control cats contained 99% type I, 1% IIa, and < 1% hybrid fibers (containing both type I and II MHCs). Following ST there were 67% type I, 17% IIa, 3% IIb, and 13% hybrid fibers. After SI, 48% of the fibers were type I, 11% were IIa, 1% were IIb, 25% were hybrid, and 15% contained embryonic MHC. Thus, normal levels of neuromuscular activity appear to be necessary for maintenance of the normal adult MHC profile in some fibers. Complete inactivation results in developmental MHC isoform expression in some fibers. Therefore, the dependence of a fiber on activity as a source of MHC modulation differs substantially among fibers even in a relatively homogeneous muscle.

Animals↗
PubMed2002

Pelotomaculum thermopropionicum gen. nov., sp. nov., an anaerobic, thermophilic, syntrophic propionate-oxidizing bacterium.

An anaerobic, thermophilic, syntrophic propionate-oxidizing bacterium, strain SI(T), isolated previously from granular sludge in a thermophilic upflow anaerobic sludge blanket (UASB) reactor, was characterized. The strain could grow fermentatively on pyruvate and fumarate in pure culture. The strain grew on propionate, ethanol, lactate, 1-butanol, 1-pentanol, 1,3-propanediol, 1-propanol and ethylene glycol in co-culture with the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus strain deltaH(T). The optimum temperature for growth was 55 degrees C and the pH optimum was 7.0. The G+C content of the DNA was 52.8 mol %. Strain SI(T) contained MK-7 and MK-7(H4) as the major quinones and contained iso-C15:0 as the major fatty acid. Based on 16S rDNA sequence analysis, strain SI(T) formed a novel lineage within the gram-positive, spore-forming, sulphate-reducing bacterial group Desulfotomaculum. However, the strain lacked the ability to conduct dissimilatory sulphate reduction. Instead, it could reduce fumarate to succinate with concomitant growth on several organic substances as electron donor. These phenotypic and genetic properties support the formation of a novel species of a new genus, for which the name Pelotomaculum thermopropionicum gen. nov., sp. nov. is proposed. The type strain is strain SI(T) (= DSM 13744T = JCM 10971T).

Base Composition↗
PubMed1990

Pyogenic sacroiliitis in a rural population.

We describe 10 cases of pyogenic sacroiliitis occurring in a rural population. Seven were male and 3 were female with a mean age of 22.4 years. None was a recent intravenous drug abuser. Five patients had a history of recent pelvic trauma. 99mTechnetium scintiscans revealed increased sacroiliac (SI) joint uptake in 8 of 8 cases. Blood cultures were positive in 60% of patients. Staphylococcus aureus was isolated in 7 cases from blood and/or SI aspirates and Hemophilus influenzae type B in one case. Nine of 10 patients recovered completely. One underwent arthrodesis for recurrent SI pain without evidence of relapse of infection. Median followup was 18 months.

Adolescent↗
PubMedDate not supplied

Dimensions of hostility in men, women, and boys: relationships to personality and cardiovascular responses to stress.

Ratings of Potential for Hostility and Hostile Style based on responses during the Type A Structured Interview (SI) are related to incidence of coronary heart disease morbidity and mortality. As there are very limited data on what precisely the SI ratings of hostility mean, the present study evaluated, in a sample of middle-aged men and women, and adolescent boys, a) the distributions of SI ratings of hostility according to gender and age group; b) their relationships to other hostility and personality scores; and c) their relationships to heightened cardiovascular responses to psychological stressors, which are thought to be a major mechanism linking behavior and coronary heart disease. Results showed that men are higher than women and boys in Potential for Hostility and Hostile Style ratings, which are, by and large, unrelated to standardized questionnaire measures of hostility and anger expression. Men (but not women or boys) who exhibited elevated systolic blood pressure during standardized laboratory stressors tended to be rated as high on Hostile Style. We conclude that SI Hostile Style ratings are measuring a unique aspect of personality, one with apparent importance for coronary heart disease and perhaps for men's cardiovascular responses during stress.

Adolescent↗
PubMed2000

Ca(2+) channels involved in the generation of the slow afterhyperpolarization in cultured rat hippocampal pyramidal neurons.

The advantages of using isolated cells have led us to develop short-term cultures of hippocampal pyramidal cells, which retain many of the properties of cells in acute preparations and in particular the ability to generate afterhyperpolarizations after a train of action potentials. Using perforated-patch recordings, both medium and slow afterhyperpolarization currents (mI(AHP) and sI(AHP), respectively) could be obtained from pyramidal cells that were cultured for 8-15 days. The sI(AHP) demonstrated the kinetics and pharmacologic characteristics reported for pyramidal cells in slices. In addition to confirming the insensitivity to 100 nM apamin and 1 mM TEA, we have shown that the sI(AHP) is also insensitive to 100 nM charybdotoxin but is inhibited by 100 microM D-tubocurarine. Concentrations of nifedipine (10 microM) and nimodipine (3 microM) that maximally inhibit L-type calcium channels reduced the sI(AHP) by 30 and 50%, respectively. However, higher concentrations of nimodipine (10 microM) abolished the sI(AHP), which can be partially explained by an effect on action potentials. Both nifedipine and nimodipine at maximal concentrations were found to reduce the HVA calcium current in freshly dissociated neurons to the same extent. The N-type calcium channel inhibitor, omega-conotoxin GVIA (100 nM), irreversibly inhibited the sI(AHP) by 37%. Together, omega-conotoxin (100 nM) and nifedipine (10 microM) inhibited the sI(AHP) by 70%. 10 microM ryanodine also reduced the sI(AHP) by 30%, suggesting a role for calcium-induced calcium release. It is concluded that activation of the sI(AHP) in cultured hippocampal pyramidal cells is mediated by a rise in intracellular calcium involving multiple pathways and not just entry via L-type calcium channels.

Action Potentials↗
PubMed1987

Personality, type A behavior, and coronary heart disease: the role of emotional expression.

The nature of the relation between personality factors and coronary heart disease (CHD, the nation's greatest killer) is one of the most important if controversial issues in the field of psychology and health. Although there is still a great deal of conceptual confusion, progress is being made in refining the key components of a predisposition to heart disease. In this article we examine the construct of a coronary-prone personality in the context of the relations among personality, emotional expression, and disease. Special consideration is given to mode of measurement of the Type A behavior pattern--Structural Interview (SI) versus Jenkins Activity Survey (JAS)--and to components and non-Type A correlates of the general coronary-prone construct. Fifty middle-aged men who had had a myocardial infarction were compared with 50 healthy controls in terms of relevant aspects of their psychological functioning. Results indicate that the SI is better than the JAS as a predictor of coronary heart disease (CHD) because of its attention to emotional expressive style. Traditional emphases on hurry sickness in coronary proneness are deemed wholly inadequate. Furthermore, the results indicate that depression, anxiety, or both may relate to CHD independently of and in addition to Type A behavior. Other aspects of personality and social support are also discussed in the context of improving the construct of coronary proneness.

Adaptation, Psychological↗
PubMed1984

Serological characterization of Streptococcus mutans serotype polysaccharide g and its different molecular weight forms.

The serotype polysaccharide g from Streptococcus mutans 6715 was found to cross-react with serotype polysaccharide a from S. mutans HS6 and serotype polysaccharide d from S. mutans B13. Double immunodiffusion experiments indicated that the serotype polysaccharide g consisted of the following: (i) the type-specific g site; (ii) a cross-reactive site g-a that was in common with polysaccharide a; (iii) a cross-reactive site g-d that was in common with polysaccharide d; and (iv) a cross-reactive site g-(a-d) that was in common with both polysaccharides a and d. Moreover, by a procedure involving several column chromatography steps, six polysaccharide-containing fractions showing reactivity with anti-g serum were found. By gel filtration, the molecular weight estimates of fractions LI, LII, LIII, SI, SII, and SIII were 2 X 10(6), 5 X 10(5), 6 X 10(4), 3 X 10(4), 1.4 X 10(4), and 1 X 10(4), respectively. Double immunodiffusion analysis indicated that LI, LII, and LIII contained the four antigenic sites of the putative polysaccharide g. LII also contained another additional immunodominant region, designated site x. The analysis also suggested that fraction SI lacked the type-specific site g, fraction SII lacked sites g and g-a, and fraction SIII lacked sites g, g-a, and g-d.

Antigens, Bacterial↗
PubMed2003

A personal thermoluminescence dosimeter using LiF:Mg,Cu,Na,Si detectors for photon fields.

A new personal thermoluminescence (TL) dosimeter for photon fields using LiF:Mg,Cu,Na,Si TL detector was developed by taking advantage of its dosimetric properties including energy dependencies. Solid pellet type LiF:Mg,Cu,Na,Si detector was developed and fabricated at Korea Atomic Energy Research Institute (KAERI) and has been studied on its dosimetric properties such as TL grow curve, dose response, energy response and reusability. Its dosimetric properties show the feasibility of application of LiF:Mg,Cu,Na,Si TL detector to personal dosimetry fields. A new dosimeter using LiF:Mg,Cu,Na,Si TL detector was designed and tested through irradiation experiments. This multi-element TL dosimeter allows the measurement of a personal dose equivalent Hp(d) in photon fields. Based on the experimental results of the proposed dosimeter, it was demonstrated that a personal TL dosimeter using sintered LiF:Mg,Cu,Na,Si TL detector is appropriate to estimate personal dose equivalent for wide range energy of photon fields.

Copper↗
PubMed2001

Synthesis of Ferrierite-Type Zeolite in the Presence of a Catalytic Amount of Pyrrolidine and Sodium Bis(2-ethyhlhexyl) Sulfosuccinate.

Synthesis of ferrierite (FER) type zeolite with varying Si to Al ratios in the presence of a catalytic amount of pyrrolidine and sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in aqueous media is reported. The surfactant moieties direct pyrrolidine molecules in a particular fashion, resulting in a sixfold decrease in the required amount of template as compared to conventional procedure, for FER crystallization. The product obtained was highly crystalline and pure. In the presence of AOT alone, ferrierite co-crystallized with the ZSM-5 phase, indicating AOT is not acting as a structure-directing agent and a small concentration of pyrrolidine ( approximately 2 wt%) template is essential for the ferrierite crystallization. A scanning electron micrograph showed uniformity in crystals (average 2-3 µm) consisting of broad plate type morphology. The crystal structure of FER (AOT/Py) maintains structural integrity until about 1000 degrees C. FER (AOT/Py) has been further characterized by employing XRD, XRF, IR, and TG/DTA techniques. Copyright 2001 Academic Press.

Journal Article↗
PubMed2005

[Internal fixation of sacroiliac joint disruption].

OBJECTIVE: Stabilization of the completely disrupted sacroiliac (SI) joint with two three-hole DC plates. INDICATIONS: Definitive treatment of the posterior pelvic ring in type C injuries (AO classification) with complete SI joint disruption, transiliac or transsacral fracture-dislocation of the SI joint with an insignificant, small fragment. Emergency stabilization of the SI joint following a laparotomy. CONTRAINDICATIONS: Poor general health of patient. Local soft-tissue damage. Rotationally unstable type B pelvic injuries. SURGICAL TECHNIQUE: Supine. Anterolateral approach to the iliac crest. Subperiosteal detachment of the iliac muscle. Debridement of the SI joint and reduction under direct vision. Stabilization of the SI joint with two three-hole DC plates inserted at an angle of 70-90 degrees. POSTOPERATIVE MANAGEMENT: Partial weight bearing on the injured side at 15 kg for 8-12 weeks with two forearm crutches. Implant removal 6-12 months after injury provided ankylosis has not occurred. RESULTS: In 27 patients with disruption of the SI joint consistent with a type C injury, the average displacement of the affected SI joint was 16 mm (8-30 mm). Complications relating to the osteosynthesis occurred as a deep infection in one patient, originating from a concomitant acetabular osteosynthesis. Iatrogenic nerve damage (lateral femoral cutaneous nerve) was present in two patients. 16 patients were followed up using radiologic techniques (pelvic, possibly inlet and outlet views, computed tomography). 13 SI joints healed in anatomic position. The malalignments observed were relatively slight (2-4 mm). There was no secondary implant failure. Almost all patients (n = 14) showed posttraumatic changes of the SI joint (osteophytes, arthrosis, ankylosis).

Adolescent↗
PubMedDate not supplied

Ethanol induced delayed cellular protection in mouse cardiac myocytes: role of inducible nitric oxide synthase.

This study has examined the hypotheses that, firstly, the ethanol induces delayed cellular protection in mouse cardiac myocytes against subsequent sustained simulated ischemia (SI). Secondly, the delayed cyto-protective effect induced by the ethanol depends more on time than the dose in mouse cardiac myocytes. Finally, ethanol-induced delayed cellular protection in mouse cardiac myocytes is mediated through inducible nitric oxide synthase (iNOS). Accordingly, we planned the following groups of BALB/c mouse cultured cardiac myocytes in our study: (a) SI, (b) 5 mM ethanol (ETOH)/15 min + SI, (c) 5 mM ETOH/30 min + SI, (d) 10 mM ETOH/15 min + SI, (e) 10 mM ETOH/30 min + SI, (f) 25 mM ETOH/15 min + SI, (g) 25 mM ETOH/30 min + SI, (h) 25 mM ETOH/60 min + SI, (i) 50 mM ETOH/15 min + SI, (j) 50 mM ETOH/30 min + SI, (k) 50 mM ETOH/60 min + SI, (l) 250 mM ETOH/15 min + SI and (m) 250 mM ETOH/30 min + SI. Another set of experiments we designed with iNOS-/- and its wild-type (iNOS+/+) mice cardiac myocytes as follows: SI, 5 mM ETOH/30 min + SI, 10 mM ETOH/30 min + SI, 25 mM ETOH/30 min + SI, 50 mM ETOH/30 min + SI and 250 mM ETOH/30 min + SI. Cellular injury was measured by the release of creatinine kinase (CK, U/l) into the medium. BALB/c mouse cardiac myocytes subjected to SI demonstrated significant increase in CK release as compared to the ethanol-treated cells. Ethanol-induced delayed cellular protection resulted in a significant (p < 0.001) attenuation in the cellular injury as indicated by reduction in the release of CK (U/l) from 9.25 +/- 0.52 to 5.16 +/- 0.44 (5 mM ETOH/30 min), from 7.50 +/- 0.43 (10 mM ETOH/15 min) to 4.16 +/- 0.64 (10 mM ETOH/30 min), from 5.91 +/- 0.41 (25 mM ETOH/15 min) to 2.50 +/- 0.58 (25 mM ETOH/30 min) and to 2.25 +/- 0.37 (25 mM ETOH/60 min), from 5.41 +/- 0.28 (50 mM ETOH/15 min) to 1.66 +/- 0.56(50 mM ETOH/30 min) and to 1.25 +/- 0.30 (50 mM ETOH/60 min), and from 5.25 +/- 0.21(250 mM ETOH/15 min) to 1.66 +/- 0.51(250 mM ETOH/30 min). Reduction in CK release from ethanol-treated iNOS-/-mouse cardiac myocytes was insignificant (p > 0.05) compared to non-treated wild-type (iNOS+/+) mouse cardiac myocytes subjected to SI alone. Our data suggest that ethanol induces delayed cellular protection in mouse cardiac myocytes against sustained simulated ischemia. Further, ethanol-induced delayed cellular protection depends more on time than the dose. Furthermore, ethanol-induced delayed cellular protection is dependent on iNOS.

Animals↗
PubMedDate not supplied

The insulin sensitivity, glucose sensitivity, and acute insulin response to glucose load in adolescent type 2 diabetes in Taiwanese.

BACKGROUND: Insulin sensitivity (SI), glucose sensitivity (SG), acute insulin response to glucose load (AIR), and obesity in adolescent type 2 diabetes patients (young diabetes, YDM) in Taiwan were studied. METHODS: Forty patients diagnosed at <22 years of age were enrolled and divided into non-obese (NOYDM, BMI < 27 kg/m(2)) and obese groups (OBYDM BMI > 27 kg/m(2)). Adult-onset type 2 diabetes patients (ADM) >40 years old (n = 41) and nondiabetic young adults (N) (n = 23) served as controls. Fasting plasma lipids, insulin, and glucose were measured. Homeostasis model assessment was calculated to estimate insulin sensitivity and beta-cell function. A frequent-sampled intravenous glucose tolerance test was performed to evaluate SI, SG, and AIR. RESULTS: SI and AIR were significantly lower in YDM and ADM than in N (0.92 +/- 0.13, 0.8 +/- 0.15 and 3.24 +/- 0.47 x 10(-4)/U/mL for SI; 40.3 +/- 20.3, 107.3 +/- 50.2, 1208 +/- 306.3 uU/min for AIR). SG of YDM and ADM were lower compared with N (0.014 +/- 0.00138, 0.0292 +/- 0.0058 vs 0.034 +/- 0.0086 min(-1) respectively). No difference was noted between YDM and ADM. SI and SG were not different in NOYDM and OBYDM. AIR was higher in OBYDM (83.6 +/- 34.3 vs -7.6 +/- 13.66 uU/min). CONCLUSIONS: YDM had defects in SI, SG, and AIR compared to N, which was similar to the pathophysiology of ADM. The results imply that YDM may be either a different subtype of diabetes or the same type of diabetes as ADM, with severe defects associated with earlier age of onset. OBYDM had higher AIR than NOYDM.

Adult↗
PubMed1994

Level of independence of motor unit properties from neuromuscular activity.

Neuromuscular activity was eliminated in the tibialis anterior muscle of adult cats for 6 months by spinal isolation (SI), i.e., complete spinal cord transections at T-12-13 and at L-7-S-1, plus bilateral dorsal rhizotomy between the two transection sites. One motor unit from each muscle was isolated using ventral root teasing procedures and physiologically tested. The fibers belonging to each motor unit were visualized in PAS-stained sections by the loss of glycogen following prolonged repetitive stimulation. Qualitatively, the normal enzymatic interrelationships among fibers identified by myosin heavy chain composition were unchanged by SI. Generally, each motor unit from SI cats were of a single myosin immunohistochemical type. The same physiological motor unit types that typify control muscles were found in SI cats. In SI compared to control cats, there was approximately a 10% increase in the number of muscle fibers expressing fast myosin. Mean fiber activity levels of ATPase and SDH for a given fiber type (based on MHC antibody reactions) decreased by approximately 10% and 25%, whereas GPD activity increased approximately 35%. It is concluded that differential levels or patterns of activity are not essential to maintain the range of histochemical and physiological motor unit types found in the tibialis anterior of normal adult cats.

Action Potentials↗
PubMed2000

New insights on the structure of the mouse silver locus and on the function of the silver protein.

The melanosomal proteins encoded by the silver locus play important roles in melanogenesis. The human locus yields two proteins, PMEL17 and GP100, by alternative mRNA splicing. The mouse si locus was reported to encode a Pmel17 protein, and later gp87, a GP100 homologue. When we re-examined the products of wild-type and silver-mutant mouse si loci, RT-PCR of wild-type RNA and genomic DNA sequence accounted for gp87 but excluded the occurrence of Pmel17. Analysis of cDNA from the silver (si/si) melanocyte line, melan-si, showed that the pathogenic mutation is a G to A substitution at nt 1808, which yields a premature stop codon and a predicted protein truncated in the C-terminus. This was confirmed by reaction of a specific anti-gp87 antiserum with si/si melanocyte extracts. To further explore gp87 function, we compared the DHICA oxidase activity of extracts from B16, melan-si (heterozygous for the brown mutation and homozygous for the silver mutation) and Cloudman S91 cells (homozygous for the brown mutation), since both TRP1 and gp87 are thought to be involved in DHICA oxidation/polymerization. Cloudman extracts do not oxidize significantly DHICA and its methyl ester, supporting the involvement of native mouse TRP1 in DHICA oxidation. Extracts from B16 and melan-si do not show significant differences for the oxidation of free acid and methylated dihydroxyindoles, indicating that the mechanism is not decarboxylative. Melan-si extracts are very efficient in catalyzing dihydroxyindole oxidation, in spite of being heterozygous for the TRP1 mutation, consistent with a stablin effect for the wild-type gp87 protein. On the other hand, aggregated and degraded forms of that mutant gp87 protein are found in the cytosolic fraction of melan-si, suggesting that misrouting and aberrant processing of the gp87 and tyrosinase may also be related to the high DHICA oxidase activity of these melanocytes.

Alternative Splicing↗
PubMed1999

Clinical outcomes of steroid-insensitive asthma.

BACKGROUND: Steroid insensitivity increasingly is being recognized in patients with severe, chronic asthma. Virtually no data exist regarding the clinical outcomes of steroid insensitive (SI) asthma despite clear expectations of poorer longitudinal course for this condition. METHODS: We obtained 2-year follow-up data from 34 pediatric patients who had been evaluated for steroid insensitivity at a national asthma referral center. Outcomes evaluated included current oral glucocorticoid (GC) dose; number of GC bursts, emergency room visits, and hospitalizations for asthma in the prior 12 months; Asthma Functional Severity; Pediatric Asthma Quality of Life; and Pediatric Asthma Caregiver's Quality of Life. RESULTS: At follow-up, patients with SI asthma and their caregiving parent both reported poorer quality of life (QOL) compared with those with steroid sensitive (SS) asthma (adolescent: 4.6 +/- 0.4 versus 5.6 +/- 0.3; P < .05; caregiver: 5.1 +/- 0.4 versus 6.2 +/- 0.2; P < .05). Steroid-insensitive patients showed no significant difference in GC dose, number of GC bursts, emergency room visits or hospitalizations, or Asthma Functional Severity compared with SS patients. CONCLUSIONS: Steroid insensitivity was associated with significantly poorer QOL at 2-year follow-up. Steroid insensitive patients did not show poorer clinical outcomes compared with SS patients as assessed by current steroid requirements and health care utilization. Overall, the observed pattern of results suggests that SI asthma may be a worse form of asthma because a more fixed pattern of lung obstruction has developed. Further longitudinal study of the clinical and cellular outcomes of SI asthma is needed to more fully characterize the types and magnitude of risks associated with SI status.

Adolescent↗
PubMed2005

Mechanism of proteasomal degradation of inositol trisphosphate receptors in CHO-K1 cells.

myo-Inositol 1,4,5-trisphosphate receptor (IP3R) degradation occurs in response to carbachol (Cch) stimulation of CHO-K1 cells. The response was mediated by endogenous muscarinic receptors and was blocked by atropine or proteasomal inhibitors. We have used these cells to identify the sites of ubiquitination on IP3Rs and study the role of Ca2+ and substrate recognition properties of the degradation system using exogenously expressed IP3R constructs. Employing caspase-3 for IP3R cleavage, we show that Cch promotes polyubiquitination in the N-terminal domain and monoubiquitination in the C-terminal domain. The addition of extracellular Ca2+ to Ca2+-depleted Chinese hamster ovary (CHO) cells initiates IP3R degradation provided Cch is present. This effect is inhibited by thapsigargin. The data suggest that both a sustained elevation of IP3 and a minimal content of Ca2+ in the endoplasmic reticulum lumen is required to initiate IP3R degradation. Transient transfection of IP3R constructs into CHO cells indicated the selective degradation of only the SI+ splice variant of the type I IP3R. This was also the splice form present endogenously in these cells. A pore-defective, nonfunctional SI+ IP3R mutant (D2550A) was also degraded in Cch-stimulated cells. The Cch-mediated response in CHO cells provides a convenient model system to further analyze the Ca2+ dependence and structural requirements of the IP3R proteasomal degradation pathway.

Alternative Splicing↗