PubMed Health⌕ Search

Biomedical subjects

M Pan

Publications and source records attributed to M Pan.

At least 19 recordsLinked to original sources
PubMed2003

Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts.

BACKGROUND: Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias caused by mutations in four differentiation-specific keratin genes. Two major clinical subtypes of PC have been generally recognized. Symmetrically thickened fingernails and toenails are the defining characteristic of PC type 2 (PC-2) with onset at infancy. Pilosebaceous cysts are the best hallmark of PC-2, but they usually occur at puberty. OBJECTIVES: To report a Chinese pedigree of PC-2 with unusually early onset sebaceous cysts and to explore the genetic mutation and its phenotype. METHODS: Exon 1 of keratin 17 was amplified by polymerase chain reaction (PCR) from genomic DNA from the three patients in the pedigree, the proband, his half-sister and his younger son, two unaffected members in the pedigree and 50 unrelated and unaffected people. PCR products were directly sequenced to detect the mutation. RESULTS: Direct sequencing of the PCR products revealed a heterozygous 275A-->G mutation in all three affected members. This mutation predicts the substitution of asparagine by serine in codon 92 (N92S) located in the 1A domain of keratin 17. CONCLUSIONS: Mutation in the 1A domain of keratin 17 underlies the affected members' phenotype, PC-2 with early onset sebaceous cysts and late-onset thickened fingernails and toenails. The onset of the cysts is very early in some people within this family and the age at onset of thickened fingernails and toenails is variable within the family, implying the existence of modifying factors.

Adolescent↗
PubMed2001

The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct degradative pathways.

We previously showed that Omega-3 fatty acids reduce secretion of apolipoprotein B (apoB) from cultured hepatocytes by stimulating post-translational degradation. In this report, we now characterize this process, particularly in regard to the two known processes that degrade newly synthesized apoB, endoplasmic reticulum (ER)-associated degradation and re-uptake from the cell surface. First, we found that Omega-3-induced degradation preferentially reduces the secretion of large, assembled apoB-lipoprotein particles, and apoB polypeptide length is not a determinant. Second, based on several experimental approaches, ER-associated degradation is not involved. Third, re-uptake, the only process known to destroy fully assembled nascent lipoproteins, was clearly active in primary hepatocytes, but Omega-3-induced degradation of apoB continued even when re-uptake was blocked. Cell fractionation showed that Omega-3 fatty acids induced a striking loss of apoB100 from the Golgi, while sparing apoB100 in the ER, indicating a post-ER process. To determine the signaling involved, we used wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, which blocked most, if not all, of the Omega-3 fatty acid effect. Therefore, nascent apoB is subject to ER-associated degradation, re-uptake, and a third distinct degradative pathway that appears to target lipoproteins after considerable assembly and involves a post-ER compartment and PI3K signaling. Physiologic, pathophysiologic, and pharmacologic regulation of net apoB secretion may involve alterations in any of these three degradative steps.

Androstadienes↗
PubMed2001

A role for calnexin in the assembly of the MHC class I loading complex in the endoplasmic reticulum.

Heterodimers of MHC class I glycoprotein and beta(2)-microglobulin (beta(2)m) bind short peptides in the endoplasmic reticulum (ER). Before peptide binding these molecules form part of a multisubunit loading complex that also contains the two subunits of the TAP, the transmembrane glycoprotein tapasin, the soluble chaperone calreticulin, and the thiol oxidoreductase ERp57. We have investigated the assembly of the loading complex and provide evidence that after TAP and tapasin associate with each other, the transmembrane chaperone calnexin and ERp57 bind to the TAP-tapasin complex to generate an intermediate. These interactions are independent of the N:-linked glycan of tapasin, but require its transmembrane and/or cytoplasmic domain. This intermediate complex binds MHC class I-beta(2)m dimers, an event accompanied by the loss of calnexin and the acquisition of calreticulin, generating the MHC class I loading complex. Peptide binding then induces the dissociation of MHC class I-beta(2)m dimers, which can be transported to the cell surface.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Sub-Angstrom high-resolution transmission electron microscopy at 300 keV.

Sub-Angstrom transmission electron microscopy has been achieved at the National Center for Electron Microscopy (NCEM) by a one-Angstrom microscope (OAM) project using software and enhanced hardware developed within a Brite-Euram project (Ultramicroscopy 64 (1996) 1). The NCEM OAM provides materials scientists with transmission electron microscopy at a resolution better than 1 A by using extensive image reconstruction to exploit the significantly higher information limit of an FEG-TEM over its Scherzer resolution limit. Reconstruction methods chosen used off-axis holograms and focal series of underfocused images. Measured values of coherence parameters predict an information limit of 0.78 A. Images from a [1 1 0] diamond test specimen show that sub-Angstrom resolution of 0.89 A has been achieved with the OAM using focal series reconstruction.

Journal Article↗
PubMed2001

In situ transmission electron microscopy studies and real-time digital imaging.

A newly designed CCD camera has been utilized for real-time and static image acquisitions. The performance of the camera is demonstrated for heating/cooling in-situ TEM experiments performed on a commercial high strength aluminium alloy using a double tilt heating holder. The real-time digital imaging capability of the new camera should facilitate the in-situ TEM that is now re-establishing itself as a strategic tool for materials characterization.

Journal Article↗
PubMed2001

Glutamine metabolism in sepsis and infection.

Severe infection causes marked derangements in the flow of glutamine among organs, and these changes are accompanied by significant alterations in regional cell membrane transport and intracellular glutamine metabolism. Skeletal muscle, the major repository of glutamine, exhibits a twofold increase in glutamine release during infection, which is associated with a significant increase in endogenous glutamine biosynthesis. Despite an increase in glutamine synthetase activity in skeletal muscle, the intracellular glutamine pool becomes depleted, indicating that release rates exceed rates of synthesis. Simultaneously, the circulating pool of glutamine does not increase, indicating accelerated uptake by other organs. The liver appears to be the major organ of glutamine uptake in severe infection; studies in endotoxemic rodents have shown net hepatic glutamine uptake to increase by as much as 8- to 10-fold. This increase is due partially to increases in liver blood flow, but also to a three- to fourfold increase in hepatocyte System N activity in the liver. Cytokines and glucocorticoids mediate the increased uptake of glutamine by the liver in septic states as well as other compounds. Sepsis does not appear to induce an increase in System N gene expression, indicating that the increase in hepatic glutamine transport observed during severe infection is probably regulated at the protein level. The bowel displays a decrease in glutamine utilization during sepsis, a response that may be related to the decrease in circulating insulin-like growth factor-1 (IGF-1) levels that is characteristic of sepsis. Recent studies suggest that IGF-1 has a direct effect on stimulating glutamine transport across the gut lumen and thus may represent a therapeutic avenue for improving gut nutrition during severe infection. The cells of the immune system (lymphocytes, macrophages) are also major glutamine consumers during inflammatory states in which cell proliferation is increased. Under these conditions, glutamine availability can become rate limiting for key cell functions, such as phagocytosis and antibody production.

Animals↗
PubMed2000

Genome sequence of Halobacterium species NRC-1.

We report the complete sequence of an extreme halophile, Halobacterium sp. NRC-1, harboring a dynamic 2,571,010-bp genome containing 91 insertion sequences representing 12 families and organized into a large chromosome and 2 related minichromosomes. The Halobacterium NRC-1 genome codes for 2,630 predicted proteins, 36% of which are unrelated to any previously reported. Analysis of the genome sequence shows the presence of pathways for uptake and utilization of amino acids, active sodium-proton antiporter and potassium uptake systems, sophisticated photosensory and signal transduction pathways, and DNA replication, transcription, and translation systems resembling more complex eukaryotic organisms. Whole proteome comparisons show the definite archaeal nature of this halophile with additional similarities to the Gram-positive Bacillus subtilis and other bacteria. The ease of culturing Halobacterium and the availability of methods for its genetic manipulation in the laboratory, including construction of gene knockouts and replacements, indicate this halophile can serve as an excellent model system among the archaea.

Biological Evolution↗
PubMed2000

Inhibition of translocation of nascent apolipoprotein B across the endoplasmic reticulum membrane is associated with selective inhibition of the synthesis of apolipoprotein B.

In HepG2 cells, inhibition of apolipoprotein B100 (apoB) translocation across the endoplasmic reticulum by an microsomal triglyceride transfer protein (MTP) inhibitor (CP-10447) in the presence of N-acetyl-leucinyl-norleucinal, a proteasomal inhibitor, results in accumulation of newly synthesized apoB in the translocation channel. Here we demonstrated that such accumulation led to a specific reduction of apoB synthesis. ApoB mRNA levels remained unchanged, but we observed reduced rates of elongation of nascent apoB in puromycin-synchronized cells pretreated with MTP inhibitor. This observation was consistent with a longer half-ribosome transit time for the synthesis of apoB in MTP-inhibited cells. Initiation of translation of apoB mRNA was not impaired by MTP inhibition. Overall, these findings suggest that translocation arrest of apoB in the endoplasmic reticulum channel can exert a selective and negative effect on the synthesis of apoB at the stage of elongation.

Apolipoproteins B↗
PubMed2000

Transcatheter occlusion of complex atrial septal defects.

Percutaneous device occlusion of secundum atrial septal defects (ASDs) is becoming an accepted alternative to surgical closure. This method allows us to evaluate patients with complex conditions for treatment. From a total of 70 patients with ASD evaluated for percutaneous closure, we selected for analysis 28 who had complex conditions. The mean age was 36+/-23 yr (range, 4-72). Six had heart failure, and of these six, three had atrial fibrillation. At cardiac catheterization, the pulmonary pressure was 47+/-24 mm Hg, and the QP/QS was 1.7+/-0.4; two patients had bidirectional shunt and systemic pulmonary pressure. Two patients received a buttoned device and 26 an Amplatzer septal occluder. The groups of patients with complex conditions were separated into the following groups. Group I (n = 4) underwent combined treatment of associated anomalies. Two patients had pulmonary stenosis, one had mitral stenosis, and one had an aortic root-left atrium fistula. They were treated in or during with the same procedure by combined transcatheter techniques (balloon valvuloplasty and fistula occlusion) before ASD occlusion. Group II (n = 9) had multiple defects (cribiform or two separate holes). They were treated with a single device in five instances and with two separate devices in four cases. Group III (n = 14) had large (32+/-3 mm) single defects. Nine of them underwent successful implantation using a device 33+/-3 mm in diameter; in the remaining five patients the device was removed because of instability. Group IV (n = 3) had residual defects after previous partial device occlusion. All three defects were successfully occluded with a second device. No movement or interference with the first device was observed. Group V (n = 6) had severe pulmonary hypertension (86+/-16 mm Hg). Immediately after ASD occlusion we observed significant relief in these patients (67+/-14 mm Hg; P<0.01). There were no major complications; all 23 patients with successful implants were discharged without symptoms 2-7 days later; one patient with atrial fibrillation recovered sinus rhythm. The follow-up (8+/-5 mo) Doppler echo study showed complete ASD occlusion in 22 patients and a peak pulmonary pressure of 30+/-14 mm Hg. We conclude that transcatheter occlusion of ASDs is an effective and safe treatment for patients with complex anatomic or physiopathologic conditions, as evaluated by short-term follow-up.

Adolescent↗
PubMed2000

Effects of deprivation of neonatal nerve growth factor on the expression of neurotrophin receptors and brain-derived neurotrophic factor by dental pulp afferents of the adult rat.

The dental pulp is richly innervated by peptidergic nociceptive neurones that are of special interest because of their central role in dental pain and because they have some features that are not typical of other somatic nociceptors. Here, (35)S-riboprobes were used to determine whether pulpal afferents of adult (2-month-old) rats express the nerve growth-factor (NGF) receptors, p75(NTR) and trkA, which are characteristic of peptidergic nociceptors, and additionally, whether these cells express receptors (trkB and trkC) for other members of the neurotrophin family. In order to begin characterizing the postnatal role of NGF in regulating these neurones, the susceptibility of pulpal afferents to antiserum-mediated early postnatal NGF depletion spanning the period of pulpal innervation development was also examined. In control animals, about 200 trigeminal ganglion cells were labelled after application of the retrograde tracer Fluoro-gold to the first maxillary molar. Among the labelled cells, 79% had positive hybridization signals for p75(NTR), 72% for trkA, 34% for trkB, 1% for trkC, and 77% for BDNF. Neonatal NGF depletion reduced the number of retrogradely labelled pulpal afferents by 33%, with numbers of smaller neurones being most strikingly subnormal. This reduction could be attributed to a partial depletion of the neurone population that expressed p75(NTR) and trkA. Consistent with reports that NGF-responsive neurones also express BDNF, NGF deprivation resulted in a reduction in the number of pulpal afferents that expressed BDNF to an extent similar to that seen for trkA. In contrast, anti-NGF exposure had little effect on the number of pulpal afferents that expressed trkB. These findings indicate that most pulpal afferents in the adult express the NGF receptors p75(NTR) and trkA, and thus have a continuing potential susceptibility to NGF-mediated regulation of functions such as neuropeptide and BDNF synthesis. However, only a subpopulation of this group of neurones requires NGF in order to develop connections to the pulp during the neonatal period. Few, if any, pulpal afferents express the high-affinity neurotrophin-3 (NT3) receptor trkC, although many have large cell bodies typical of NT3-responsive sensory neurones. A small subpopulation of pulpal afferents seems to express no neurotrophin receptors, yet it is unlikely that these cells belong to the class of small sensory cells known to bind isolectin IB4.

Age Factors↗
PubMed2000

Percutaneous balloon-expandable stents for sealing of acute aortic dissection.

Acute aortic dissection is a highly lethal disease. When dissection involves only the descending aorta and there are no ischemic complications, medical management may be the treatment of choice. However, a high risk of expansion or rupture of the dissection remains. When renal or limb ischemic complications do appear, surgery has been the only option, despite high mortality and morbidity. Percutaneous placement of stents for sealing an acute aortic dissection might be an alternative to surgical treatment. We treated 2 patients with acute type B aortic dissection by stent-fixation of the proximal and distal descending aorta. In both patients, there was evidence of persistent flap fixation at midterm follow-up.

Acute Disease↗
PubMed2000

[Multivariate analysis of prognostic factors in renal cell carcinoma].

OBJECTIVE: To assess the effect of prognostic factors on renal cell carcinoma (RCC). METHODS: 316 cases of RCC were reviewed retrospectively. Their survival rates were calculated by Kaplan-Meier method and statistical differences were determined by Log-rank test. Significant prognostic factors were evaluated by Cox's multivariate proportional hazard model. RESULTS: After 40.3 +/- 18.5 month follow-up, the overall 5-year survival rate was 62.3%. By multivariate analysis, nine factors were included in Cox's multivariate proportional hazard model. M was the most important prognostic factor in RCC (P = 0.0013), and the others in turn were T (P = 0.0182), age (P = 0.0347), performance status (P = 0.0423), N (P = 0.0471), lymphadenectomy (P = 0.0542), grade (P = 0.0775), serum albumin (P = 0.1536), and serum creatinine (P = 0.4543). CONCLUSIONS: The significant prognostic factors in RCC were T, N, and M. Age and performance status showed the effect on prognosis of RCC. Lymph-node dissection also revealed a meaningful effect on relative lower stage of RCC.

Adult↗
PubMed2000

[Evaluation of side-effects after 131I-therapy for differentiated thyroid carcinoma].

The purpose of this study was to evaluate the side-effects of differentiated thyroid carcinoma after treatment with 3.7-7.4 GBq of 131I. A total of 342 patients were treated with 131I from May, 1989 to January, 1999. The acute side-effects, the short-term and long-term side-effects were analyzed. The follow-up lasted 1-10 years with an average of 5.4 years. The results showed that thyroiditis occurred predominantly in the patients with a rate of 131I uptake > 30%, whereas sialoadenitis occurred more prevalently in the patients with a rate of 131I uptake < 30% (P < 0.001). The rates of nausea, vomiting, diarrhea and gastralgia were 12.2%, 5.2%, 3.5% and 2.7% respectively. There were no significant changes in the hemogram after treatment, compared against that before treatment. The overall rates of transient platelet abnormalities and leukopenia were 10.4% and 4.0% respectively, but the rates of the abnormalities in the patients with cumulative doses of 131I > 18.5 GBq were significantly higher than those in patients with cumulative doses of 131 I < 18.5 GBq. The lower rate of acute and short-term side-effects and the absence of long-term side-effects in this study indicate that 131I can be safely used to treat differentiated thyroid carcinoma.

Adenocarcinoma, Papillary↗
PubMed1999

Course and composition of the nerves that supply the mandibular teeth of the rat.

The rodent dentition has become an important model for investigations of interactions between dental tissues and peripheral neurons. Although experimental nerve injury has been widely used for such studies, there is uncertainty about the courses of nerve fibers supplying the mandibular teeth. In order to clarify this, we used a mixture of monoclonal antibodies against neurofilament proteins to enhance demonstration of nerve fibers so that small nerves could be readily traced in serial frozen sections of mandibles of Sprague Dawley rats ranging in age from embryonic day (E) 18 to postnatal day (P) 90. The 1st molar and anterior portion of the 2nd molar were innervated by small nerves that emerged as distinct branches of the IAN trunk at or near the mandibular foramen. In contrast, the nerve supply to the 3rd molar and posterior part of the 2nd molar was a branch of the lingual nerve that bypassed the mandibular canal altogether. The IAN trunk split into the mental nerve and a large branch to the incisor about 2 mm anterior to the mandibular foramen. Thick branches of the incisor nerve descended into the incisor socket to form a dense plexus of nerve fiber bundles extending along the length of the incisor periodontium. The sparse pulpal innervation of the incisor was provided by a few thin fascicles that emerged from the caudal portion of the periodontal plexus to enter the incisor apex. The dental branches of the IAN and lingual nerve seen in the adult were well established and readily identifiable at age E18 even though their targets were limited to the follicles of the developing teeth. These studies show that the trigeminal branches that supply the mandibular teeth can be identified at a wide range of ages as distinct nerves at a considerable distance proximal to their targets. This detailed information on the courses taken by the dental nerves can provide an anatomical basis for increased precision in characterization and perturbation of neural pathways from the molars and incisor.

Animals↗
PubMed1999

Simple and complex stent strategies for bifurcated coronary arterial stenosis involving the side branch origin.

Coronary lesions located in major bifurcations constitute a challenge for the use of stents. Although the occlusion of a side branch covered by a stent is infrequent, the maintenance of a patent, stenosis-free bifurcation may result in a complex procedure. Between September 1994 and April 1998, 70 patients were treated by stent implantation for coronary bifurcation stenosis. The side branch always had a diameter >2 mm. The pairs of treated arteries were: left anterior descending (LAD)/diagonal artery in 32 patients, circumflex/obtuse marginal in 26, right coronary/posterior descending artery in 5, and LAD/circumflex in 7. We applied 2 different techniques of stent implantation: (1) deployment of 1 stent in the parent vessel covering the takeoff of the side branch and subsequent angioplasty of the side branch across the metallic structure (group A, n = 47 patients), and (2) implantation of 1 stent at the ostium of the side branch and complete reconstruction of the entire bifurcation with additional implantation of 1 or 2 stents at the parent vessel (group B, n = 23 patients). There were no significant differences between groups at baseline variables. Procedural success was similar in both groups: 42 (89%) in group A versus 21 (91%) in group B. However, major cardiac events at 18 months follow-up were higher in group B (event-free probability 44% vs 75%, p <0.05). Selected patients with coronary stenosis at major bifurcations can be treated with an acceptable rate of primary and late success. Complex techniques providing radical stent reconstruction of the bifurcation seems to provide no advantages over the simpler stent jail followed by ostial side branch balloon dilation.

Aged↗