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Biomedical subjects

P C Chen

Publications and source records attributed to P C Chen.

At least 19 recordsLinked to original sources

Theoretical study of the internal rotational barriers in nitrotoluenes, nitrophenols, and nitroanilines.

The molecular geometries and internal rotational barriers of the nitro group of 3-nitrotoluene (3-NT), 4-nitrotoluene (4-NT), 3-nitrophenol (3-NP), 4-nitrophenol (4-NP), 3-nitroaniline (3-NA), and 4-nitroaniline (4-NA) were calculated by five different types of density functional theory (DFT) methods with three different levels of basis sets. Analyses of the torsional angles of the nitro, methyl, amino, and hydroxyl groups indicate that 3-NP, and 4-NP are planar molecules, but 3-NT, 4-NT, 3-NA, and 4-NA are not planar molecules. Internal rotational barriers of the nitro group were calculated as the V2 barrier, and the NO2 torsional potentials for each molecule were given. The heights of the V2 barrier vary with the DFT methods, the basis sets, and the kinds and positions of substituents. The average values of the V2 barriers for 3-NT, 4-NT, 3-NP, 4-NP, 3-NA, and 4-NA are 6.44, 6.92, 6.64, 7.93, 6.38, and 9.13 kcal/mol, respectively. Torsional potentials of the OH and NH2 groups of nitrophenol and nitroaniline derivatives were also studied by a B3LYP/6-31G* approach. Except for the OH group in 2-NP, these derivatives have the V2 barrier.

Journal Article↗

Thymoma is associated with an increased risk of second malignancy.

BACKGROUND: An association between thymoma and second malignancy has been suggested but has not been validated. Whether the relation is due to treatment or to other thymoma-associated conditions is unclear. METHODS: The authors studied 192 consecutive patients with thymoma and compared the incidence of second malignancies with those of 206 patients who underwent thymectomy for nonthymomatous conditions and 1426 patients with nasopharyngeal carcinoma (NPC). Detailed clinicopathologic features of thymoma patients with second malignancies were described. RESULTS: Additional malignancies were detected in 15 of 192 patients (8%) during their clinical courses. The risk for those patients was significantly greater compared with the risk for patients with nonthymomatous conditions (adjusted odds ratio [OR], 3.81; 95% confidential intervals [95%CI], 1.05-13.81; P = 0.042) and patients with NPC (adjusted OR, 4.89; 95%CI, 2.26-10.53; P < 0.0001) after adjustment for age, gender, length of follow-up, myasthenia gravis, and radiation therapy. The occurrence of second malignancies did not correlate with histologic type or stage of thymoma, radiation therapy, or myasthenia gravis. CONCLUSIONS: Thymoma is associated with an increased risk of second malignancy. The association cannot be attributed to the effect of thymectomy or radiation therapy. Patients with thymoma, even if it is benign, should be followed regularly to facilitate the early detection of other malignancies.

Adult↗

Correlation of abnormal intracranial vessel velocity, measured by transcranial Doppler ultrasonography, with abnormal conjunctival vessel velocity, measured by computer-assisted intravital microscopy, in sickle cell disease.

The Stroke Prevention Trial has confirmed that utilization of transcranial Doppler ultrasonography (TCD), which examines blood flow in large intracranial vessels, can identify children with sickle cell disease (SCD) who are at high risk of developing a premature stroke. It is not known to what extent the vasculopathy in SCD involves small vessels and whether the abnormalities, if present, correlate with large-vessel vasculopathy. Eighteen children with SCD were examined with TCD to determine middle cerebral artery (MCA) velocity and computer-assisted intravital microscopy (CAIM) to determine bulbar conjunctival vessel velocity during the same visit for vasculopathy correlation. High MCA velocity (> or = 200 cm/sec) was found by TCD in 4 patients who also showed abnormal conjunctival velocity (< 0.2 mm/sec or intermittent trickle flow) by CAIM. Three patients had conditional (> or = 170 cm/sec and < 200 cm/sec) MCA velocity: 2 showed abnormal (trickle) and 1 showed normal conjunctival velocity (1.9 mm/sec). One patient with unmeasurable MCA velocity had abnormal (trickle) conjunctival velocity. Of the remaining 10 patients who had normal MCA velocity, 2 showed abnormal (0.05 mm/sec and 0.1 mm/sec) and 8 showed normal conjunctival velocities (1.1-2.4 mm/sec). The MCA velocities correlated significantly with bulbar conjunctival flow velocities (P < or =.008, Fisher exact test). A correlation exists between MCA (large-vessel) and conjunctival (small-vessel) flow velocities. CAIM is a noninvasive quantitative technique that might contribute to the identification of SCD patients at high risk of stroke. Small-vessel vasculopathy might be an important pathological indicator and should be further explored in a large-scale study. (Blood. 2001;97:3401-3404)

Adolescent↗

Multiple colonic ulcers caused by Churg-Strauss syndrome in a 15-year-old girl.

Churg-Strauss syndrome (CSS), or allergic granulomatous angiitis, is an uncommon vasculitic syndrome that is found mainly in middle-aged adults. We describe a 15-year-old girl with CSS, diagnosed by histological findings and characteristic clinical features. The patient experienced two episodes of catastrophic gastrointestinal vasculitis, resulting in resection of 150 cm of small intestine and right hemicolectomy. Colonoscopic examination showed multiple colonic ulcers with active bleeding. The clinical course of the patient was grave and refractory to the therapy of steroid and cytotoxic drugs. In the world literature only two patients with multiple colonic ulcers caused by CSS have been reported, and very rare cases of childhood-onset CSS have been published. We reviewed CSS in children and found that the prognosis was poorer than that in adults.

Adolescent↗

In vivo proton MR spectroscopy of chorea-ballismus in diabetes mellitus.

The most common cause of chorea-ballismus (CB) is a vascular lesion; it is also associated with nonketotic hyperglycaemia in diabetes mellitus (DM) and may be the first manifestation of this disorder. We describe the CT, MRI and proton MR spectroscopy (1H-MRS) of CB in eight patients. Six had hemichorea-hemiballismus (HC-HB) and two bilateral CB. Single-voxel (SV) 1H-MRS was performed using point-resolved spectroscopy (PRESS). Voxels were positioned in the basal ganglia of the patients and control subjects. PRESS was also used to obtain spectroscopic imaging (1H-MRSI) of the slice of interest in two patients. CT showed a slightly dense striatum in all the patients with CB, and T1-weighted images revealed high signal. The CB correlated well with the neuroimaging findings. SV 1H-MRS showed the mean (+/- SD) N-acetylaspartate (NAA)/ creatine (Cr) ratio to be 1.45 +/- 0.19 in HC-HB and 1.82 +/- 0.06 on the opposite normal side (P = 0.01). The choline (Cho)/ Cr ratio was 1.3 +/- 0.12 in HC-HB and 1.11 +/- 0.13 on the opposite normal side (P = 0.005). A lactate peak was seen in seven patients. The NAA/Cr ratio was 1.44 +/- 0.15 in bilateral CB and 1.74 +/- 0.16 in the controls (P = 0.017); the Cho/Cr ratios were 1.36 +/- 0.1 and 1.19 +/- 0.07 (P = 0.015). The low NAA/Cr suggests neuronal loss or damage and the high Cho/Cr probably indicates gliosis. The presence of lactate may suggest mild ischaemia due to acute vascular events during hyperglycaemia and underlying chronic focal cerebrovascular diseases in DM.

Aged↗

Correlations between theoretical and experimental determination of heat of formation of certain aliphatic nitro compounds.

Heats of formation of energetic materials were calculated by Dewar's AM1 and Stewart's PM3 methods. In order to compare the theoretical results with the experimental ones, some correlation models were proposed in this study. Correlations were evaluated by multivariable linear regression method, considering the number of nitro groups and the use of quadratic relations involving the number of carbon, hydrogen, nitrogen, and oxygen atoms. Results indicated very precise correlations. Based on these correlations, heats of formation of some aliphatic nitro compounds can be predicted at 95% predictive interval without experimental analysis.

Journal Article↗

Protein kinase C and changes in manganese superoxide dismutase gene expression in cultured glial cells.

1. To study the role of protein kinase C (PKC) in the increase in manganese superoxide dismutase (Mn-SOD) gene expression following transient hypoxia in glial cells, we examined the mRNA levels of Mn-SOD using northern blot analysis. 2. The Mn-SOD mRNA levels were markedly increased after exposure to nitrogen gas for 5 min. 3. Pretreatment with chelerythrine or GF109203x, inhibitors of PKC, attenuated the increase in Mn-SOD mRNA following hypoxia in a concentration-dependent manner. 4. Incubation with phorbol 12-myristate 13-acetate, the PKC activator, enhanced the increase in Mn-SOD gene expression in response to transient hypoxia. 5. The results suggest that hypoxia increases Mn-SOD gene expression in cultured glial cells mainly through activation of a PKC pathway.

Cell Hypoxia↗

Human chondrocyte apoptosis in response to mechanical injury.

OBJECTIVE: The effect of mechanical injury on chondrocyte viability and matrix degradation was studied. It was proposed that mechanical injury to human cartilage explants results in chondrocyte apoptosis with associated loss of glycosaminoglycans. DESIGN: Full thickness human cartilage explants, 5 mm in diameter were subjected to a single static mechanical stress of 14 MPa for 500 ms under radially unconfined compression. Glycosaminoglycan (GAG) release and percentage of cells undergoing apoptosis were measured at 96 h after injury. To establish the time course of apoptosis, explants were subjected to 30% strain and cultured for varying intervals up to 7 days after injury. A group of loaded explants were also treated with the broad spectrum caspase inhibitor z-Vad.fmk after injury. RESULTS: Internucleosomal DNA fragmentation as one indicator of apoptosis was observed in 34% (S.D.+/-11) of chondrocytes at 96 h in response to mechanical loading at 14 MPa, compared to 4% (S.D.+/-2) in the non-loaded explants. Evidence for cell death induction via apoptosis was also obtained by electron microscopy and caspase cleavage of cytokeratin. GAG release was also higher for the loaded explants, mean 1.9% (S.D.+/-0.14) of total GAG content, compared to control explants, mean 0.8% (S.D.+/-0.28). The percentage of apoptotic cells also correlated with the level of GAG release into the culture media. The percentage of apoptotic chondrocytes demonstrated a progressive increase from 6 h to 7 days post-injury. When loaded explants were cultured in z-Vad.fmk after injury, a 50% reduction in apoptosis rates was seen. CONCLUSIONS: These results demonstrate that mechanical injury induces chondrocyte apoptosis and release of GAG from the matrix. The time course suggests that a therapeutic window may exist where apoptosis could be inhibited. This potentially identifies a new approach to chondroprotection.

Adolescent↗

Impact of mechanical trauma on matrix and cells.

Posttraumatic arthritis is one of the most common causes of secondary osteoarthritis. The contribution of cell death to matrix degradation has not been characterized fully. The current study was designed to determine the effect of mechanical injury on chondrocyte viability and matrix degradation. Full-thickness bovine and human cartilage explants, 5 mm in diameter were subjected to mechanical loads representative of traumatic joint injury. Glycosaminoglycan release and percent apoptotic cells were measured. Unilateral patellas in eight anesthetized rabbits were subjected to an impact load. Rabbits were euthanized at 96 hours after injury and patellar cartilage was harvested for analysis. The effect of a pan-caspase inhibitor, z-VAD.fmk [benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone] in preventing chondrocyte apoptosis in human articular cartilage explants was determined. A significant increase in the number of apoptotic cells was observed in response to mechanical loading. The mean in vivo apoptotic rates were 1% in control rabbits and 15% in impacted patellas. Caspase inhibition reduced chondrocyte apoptosis from 34% to 25% after mechanical injury and was associated with reduction in glycosaminoglycan release. Mechanical injury induces chondrocyte apoptosis that is sensitive to pharmacologic inhibition. This identifies a new approach to limit traumatic cartilage injury and the subsequent development of secondary osteoarthritis.

Animals↗

Polyethylene wear and variations in knee kinematics.

A six-station knee wear simulator was used to test a posterior cruciate-retaining total knee arthroplasty design. Six implants each were tested in three groups; low intensity, high intensity, and malalignment using kinematic inputs from normal gait data, more severe loading conditions, and 3 degrees varus malalignment, respectively. For each group, gravimetric wear of the polyethylene inserts was measured for 5,000,000 cycles. Knee wear testing showed significantly different results for the three groups. Low intensity group inserts had mean wear rates of 3.1 (+/- 1.2) mg per million cycles. High intensity group inserts had significantly higher mean wear rates of 7.4 (+/- 2.7) mg per million cycles. Malalignment group inserts had the highest wear rates of 9.2 (+/- 3.3) mg per million cycles. The wear generated in the knee simulator seems to be dependent on the relative motions and loads at the articulating surface. The high intensity groups were subjected to motions that included reciprocating anteroposterior translations and a higher peak axial load than the low intensity group. This resulted in increasing the amount of wear. Varus malalignment also increased the total wear significantly. These results may explain some of the wide variations in wear seen in retrieved knee implants.

Biomechanical Phenomena↗

Polyethylene contact stresses, articular congruity, and knee alignment.

Increased conformity at the tibiofemoral articulation increases contact area and reduces contact stresses in total knee arthroplasty. Malalignment, however, can increase polyethylene contact stresses. The effect of knee alignment and articular conformity on contact stresses was evaluated in a finite element model. The polyethylene insert and femoral component were modeled in high- and low-conformity conditions. An axial tibial load of 3000 N was applied across the tibiofemoral articulation at different knee positions ranging from 0 degrees, to 90 degrees, flexion, 0 to 10 mm anteroposterior translation, 0 degrees to 10 degrees axial rotation, and coronal plane angulation (liftoff). Increased conformity significantly reduced contact stresses in neutral alignment (by 44% at 0 degrees flexion and 36% at 60 degrees and 90 degrees flexion). Liftoff significantly increased contact stresses in low- and high-conformity conditions, but to a lesser degree in the high-conformity condition. Malalignment in rotation was most detrimental especially with the high-conformity insert design. Overall, increasing articular conformity reduced stresses when the knee was well-aligned. However, malalignment in axial rotation was detrimental. Mobile-bearing knee designs with increased articular congruity may result in lower contact stresses, especially the rotating-bearing designs that theoretically minimize rotational malalignment.

Biomechanical Phenomena↗

Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin.

BACKGROUND: Glycohemoglobin (gHb), measured as hemoglobin (Hb) A(1c) or as total gHb, provides a common means for assessing long-term glycemic control in individuals with diabetes mellitus. Genetic variants and chemically modified derivatives of Hb can profoundly affect the accuracy of these measurements, although effects vary considerably among commercially available methods. The prevalence of genetic variants such as HbS, HbC, and HbE, and chemically modified derivatives such as carbamyl-Hb among patient populations undergoing testing is not insignificant. Clinical laboratories and sites responsible for point-of-care testing of gHb need to be aware of the interferences produced in assays by these Hbs. APPROACH: We conducted a review of the literature describing the effects of variant Hbs on gHb assay methods commonly used in clinical laboratories. CONTENT: This review summarizes the documented effects of both common and uncommon Hb variants and derivatives on the measurement of gHb. Where known, we discuss mechanisms of interference on specific assays and methodologies. We specifically address effects of commonly encountered Hbs, such as carbamyl-Hb, HbS, HbC, HbE, and HbF, on assays that use cation-exchange chromatography, immunoassays, or boronate affinity methods for measuring gHb. SUMMARY: A variety of patient- and laboratory-related factors can adversely affect the measurement of gHb in patients harboring Hb variants or derivatives. Identification of the variant or derivative Hb before or during testing may allow accurate measurement of gHb by the selection of a method unaffected by the given variant or derivative. However, laboratories should make available alternative, non-Hb-based methods for assessing long-term glycemic control in individuals with HbCC, HbSS, or HbSC disease, or with other underlying disorders where the concentration of gHb does not accurately reflect long-term glycemic control.

Boronic Acids↗

Environmental and developmental regulation of the wound-induced cell wall protein WI12 in the halophyte ice plant.

A wounded gene WI12 was used as a marker to examine the interaction between biotic stress (wounding) and abiotic stress (high salt) in the facultative halophyte ice plant (Mesembryanthemum crystallinum). The deduced WI12 amino acid sequence has 68% similarity to WUN1, a known potato (Solanum tuberosum) wound-induced protein. Wounding, methyl jasmonate, and pathogen infection induced local WI12 expression. Upon wounding, the expression of WI12 reached a maximum level after 3 h in 4-week-old juvenile leaves, whereas the maximum expression was after 24 h in 8-week-old adult leaves. The temporal expression of WI12 in salt-stressed juvenile leaves was similar to that of adult leaves. The result suggests that a salt-induced switch from C3 to Crassulacean acid metabolism has a great influence on the ice plant's response to wounding. The expression of WI12 and the accumulation of WI12 protein were constitutively found in phloem and in wounded mesophyll cells. At the reproductive stage, WI12 was constitutively found in petals and styles, and developmentally regulated in the placenta and developing seeds. The histochemical analysis showed that the appearance of WI12 is controlled by both environmental and developmental factors. Immunogold labeling showed WI12 preferentially accumulates in the cell wall, suggesting its role in the reinforcement of cell wall composition after wounding and during plant development.

Acetates↗