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Background: Pulmonary resection after induction therapy is associated with high rates of pulmonary morbidity and mortality. However, the impact of induction therapy on the pulmonary toxicity and associated pulmonary complications has not been fully investigated in the setting of lung cancer surgery., Methods: We assessed the 66 consecutive patients who underwent a pulmonary resection after induction therapy, 48 of whom received chemoradiotherapy and 18, chemotherapy alone. Results of pulmonary function before and after induction therapy were compared, and logistic regression analyses utilized to explore the risk factors of pulmonary morbidity., Results: After induction therapy, forced expiratory volume in 1 second (FEV1) was increased significantly (from 2.28 +/- 0.61 L to 2.40 +/- 0.62 L; p < 0.05); however, percent vital capacity (%VC) and FEV1/FVC did not change significantly. The diffusing capacity of lung for carbon monoxide (D(LCO)) was decreased significantly by 21% (from 90.3% +/- 18.3% to 71.1% +/- 12.5%; p < 0.0005). Patients with respiratory complication showed lower predicted postoperative %FEV1 (49.5% +/- 11.1% versus 57.2% +/- 14.2%; p = 0.031) and predicted postoperative %Dlco (41.9% +/- 8.0% versus 55.4% +/- 10.1%; p < 0.0001) results than those without complications. Univariate and multivariate analyses revealed that predicted postoperative %D(LCO) alone was an independent factor to predict postoperative pulmonary morbidity., Conclusions: For patients who undergo a pulmonary resection after induction therapy, predicted postoperative %D(LCO) is more important to predict pulmonary morbidity rather than static pulmonary function (predicted postoperative %VC or %FEV1). The decrease in D(LCO) is thought to reflect a limited gas exchange reserve, caused by the potential toxicity of chemotherapy or chemoradiotherapy. We believe that the impact of diffusion limitation after induction therapy should to be emphasized to decrease the pulmonary morbidity.

Background: The autoimmune regulator (AIRE) gene influences thymic self-tolerance induction. In autoimmune polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first. Autoimmunity and chronic candidiasis can associate with thymomas as well. Patients with these tumours frequently also have high titre immunoglobulin G autoantibodies neutralising type I interferon (IFN)-alpha and IFN-omega, which are secreted signalling proteins of the cytokine superfamily involved in both innate and adaptive immunity., Methods and Findings: We tested for serum autoantibodies to type I IFNs and other immunoregulatory cytokines using specific binding and neutralisation assays. Unexpectedly, in 60/60 Finnish and 16/16 Norwegian APS1 patients with both AIRE alleles mutated, we found high titre neutralising immunoglobulin G autoantibodies to most IFN-alpha subtypes and especially IFN-omega (60% homologous to IFN-alpha)-mostly in the earliest samples. We found lower titres against IFN-beta (30% homologous to IFN-alpha) in 23% of patients; two-thirds of these (from Finland only) also had low titres against the distantly related "type III IFN" (IFN-lambda1; alias interleukin-29). However, autoantibodies to the unrelated type II IFN, IFN-gamma, and other immunoregulatory cytokines, such as interleukin-10 and interleukin-12, were much rarer and did not neutralise. Neutralising titres against type I IFNs averaged even higher in patients with APS1 than in patients with thymomas. Anti-type I IFN autoantibodies preceded overt candidiasis (and several of the autoimmune disorders) in the informative patients, and persisted for decades thereafter. They were undetectable in unaffected heterozygous relatives of APS1 probands (except for low titres against IFN-lambda1), in APS2 patients, and in isolated cases of the endocrine diseases most typical of APS1, so they appear to be APS1-specific. Looking for potentially autoimmunising cell types, we found numerous IFN-alpha(+) antigen-presenting cells-plus strong evidence of local IFN secretion-in the normal thymic medulla (where AIRE expression is strongest), and also in normal germinal centres, where it could perpetuate these autoantibody responses once initiated. IFN-alpha2 and IFN-alpha8 transcripts were also more abundant in antigen-presenting cells cultured from an APS1 patient's blood than from age-matched healthy controls., Conclusions: These apparently spontaneous autoantibody responses to IFNs, particularly IFN-alpha and IFN-omega, segregate like a recessive trait; their high "penetrance" is especially remarkable for such a variable condition. Their apparent restriction to APS1 patients implies practical value in the clinic, e.g., in diagnosing unusual or prodromal AIRE-mutant patients with only single components of APS1, and possibly in prognosis if they prove to predict its onset. These autoantibody responses also raise numerous questions, e.g., about the rarity of other infections in APS1. Moreover, there must also be clues to autoimmunising mechanisms/cell types in the hierarchy of preferences for IFN-omega, IFN-alpha8, IFN-alpha2, and IFN-beta and IFN-lambda1.

Objectives: We conducted a retrospective study of the clinical impact of a concomitant diagnostic and therapeutic procedure for patients with histologically unproven pulmonary nodules., Methods: Between January 2001 and December 2003, we performed 150 consecutive surgical biopsy procedures for histologically indeterminate pulmonary nodules. We compared the clinical impact of the concomitant diagnostic wedge resection followed by lobectomy (U group, n=50) with that of a scheduled standard lobectomy in those with preoperatively proven clinical stage I lung cancer during the same period (C group, n=60)., Results: There were no significant differences in dichotomous variables, whereas we found significant differences in tumor size, operative time and blood loss between the 2 groups. Complication developed in 9 in the U group and 3 in the C group (p=0.030). Hospital mortality was 2% in the U group and 0% in the C group (p=0.11)., Conclusion: Morbidity and mortality following a concomitant diagnostic and therapeutic procedure in patients with preoperatively undiagnosed lung cancer was acceptable, however, staged operations should be indicated for patients with considerable co-morbidity.

Sialidosis and galactosialidosis are lysosomal storage diseases caused by the genetic defects of lysosomal sialidase (neuraminidase-1; NEU1) and lysosomal protective protein/cathepsin A (PPCA), respectively, associated with a NEU1 deficiency, excessive accumulation of sialylglycoconjugates, and development of progressive neurosomatic manifestations; in addition, the latter disorder is accompanied by simultaneous deficiencies of beta-galactosidase and cathepsin A. We demonstrated that a few soluble N-glycosylated proteins carrying sialyloligosaccharides sensitive to glycopeptidase F (GPF) can be specifically detected in cultured fibroblasts from sialidosis and galactosialidosis cases by blotting with a Maackia amurensis (MAM) lectin. We also examined the therapeutic effects of normal gene transfer and enzyme replacement by evaluating the decreases in sialylglycoconjugates accumulated in fibroblasts with these NEU1 deficiencies. The specific N-glycosylated proteins detected on MAM lectin blotting as well as the granular lysosomal fluorescence due to an avidin-FITC/biotinylated MAM lectin conjugate in sialidosis and galactosialidosis fibroblasts disappeared in parallel with the restoration of the intracellular NEU1 activity after transfection of the recombinant NEU1 fused to HA tag sequence and the wild-type PPCA cDNA as well as administration of the recombinant PPCA precursor protein. The detection method for the abnormal sialylglycoproteins in cultured cells involving MAM lectin was demonstrated to be useful not only for biochemical and diagnostic analyses of NEU1 deficiencies but also for therapeutic evaluation of these conditions.

Higher plants respond to environmental stresses by a sequence of reactions which include the reduction of growth by affecting cell division. It has been shown that calcium ions plays a role as a second messenger in mediating various defence responses under environmental stresses. In this study, the role of calcium ions on cell cycle progression under abiotic stresses has been examined in tobacco BY-2 suspension culture cells. Using synchronized BY-2 cells expressing the endogenous calcium sensor aequorin as experimental system, we could show that oxidative and hypoosmotic stress both induce an increase of intracellular calcium and cause a delay of the cell cycle. The inhibitory effect of these abiotic stress stimuli on cell cycle progression could be mimicked by increasing the intracellular calcium concentration via application of an external electrical field. Likewise, depletion of calcium ions in the culture medium suppressed the effect of the stimuli tested. These results demonstrate that calcium signalling is involved in the regulation of cell cycle progression in response to abiotic stress.

Plants are always exposed to the menace of oxidative stress and protect themselves by activating a variety of defense responses. However, molecular mechanisms for oxidative stress-induced gene expression are largely unknown. We here studied the roles of the oxidative stress-responsive putative voltage-dependent Ca(2+) permeable channels, NtTPC1A and NtTPC1B, and cell cycle in H(2)O(2)-induced expression of antioxidant enzymes, glutathione peroxidase (GPX) and ascorbate peroxidase (APX), in tobacco BY-2 cells. H(2)O(2)-induced [Ca(2+)](cyt) rise and expression of GPX and APX were inhibited by the cosuppression of NtTPC1A/B as well as Al ion, a specific blocker for NtTPC1s, and enhanced by overexpression of AtTPC1, suggesting that NtTPC1s are the major Ca(2+)-permeable channels activated by H(2)O(2) and that Ca(2+) influx via NtTPC1s is involved in induction of H(2)O(2)-triggered gene expression. Oxidative stress-induced signal transduction mechanisms were highly dependent on the phases of the cell cycle; H(2)O(2)-induced [Ca(2+)](cyt) rise and expression of GPX and APX as well as the level of NtTPC1s transcripts correlated with each other and were maximal at G1 phase. In contrast, the cell cycle-dependence of hypoosmotic shock-induced [Ca(2+)](cyt) rise that is known to be independent of NtTPC1s was almost reverse and maximal at S phase. These results suggest that the cell cycle-dependent regulation of oxidative stress-induced [Ca(2+)](cyt) rise and expression of NtTPC1s contribute to the cell cycle dependence of H(2)O(2)-induced expression of peroxidases. Various Ca(2+)-mediated signal transduction pathways are differentially regulated by the cell cycle.

Castleman's disease is a rare lymphoproliferative disorder of unknown etiology. To our knowledge, Castleman's disease arising from the accessory spleen has not been reported in the literature. We report the case of localized Castleman's disease arising from the accessory spleen in a 34-year-old woman and discuss the characteristic findings of ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging.

The origin recognition complex (ORC) protein plays a critical role in DNA replication through binding to sites (origins) where replication commences. The protein is composed of six subunits (ORC1 to 6) in animals and yeasts. Our knowledge of the ORC protein in plants is, however, much less complete. We have performed cDNA cloning and characterization of ORC subunits in rice (Oryza sativa L. cv. Nipponbare) in order to facilitate study of plant DNA replication mechanisms. Our previous report provided a description of a gene, ORC1 (OsORC1), that encodes one of the protein subunits. The present report extends this initial analysis to include the genes that encode four other rice ORC subunits, OsORC2, 3, 4 and 5. Northern hybridization analyses demonstrated the presence of abundant transcripts for all OsORC subunits in shoot apical meristems (SAM) and cultured cells, but not in mature leaves. Interestingly, only OsORC5 showed high levels of expression in organs in which cell proliferation is not active, such as flag leaves, the ears and the non-tip roots. The pattern of expression of OsORC2 also differed from other OsORC subunits. When cell proliferation was temporarily halted for 6-10 days by removal of sucrose from the growth medium, expression of OsORC1, OsORC3, OsORC4 and OsORC5 was substantially reduced. However, the level of expression of OsORC2 remained constant. We suggest from these results that expression of OsORC1, 3, 4 and 5 are correlated with cell proliferation, but the expression of OsORC2 is not.

Background: A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event., Materials and Methods: Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis., Results: The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas., Conclusions: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.

Purpose: Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells., Patients and Methods: Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis., Results: GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n = 6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression., Conclusions: Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.

The molecular links between the cell cycle and defense responses in plants are largely unknown. Using synchronized tobacco BY-2 cells, we analyzed the cell cycle dependence of elicitor-induced defense responses. In synchronized cultured apoaequorin-expressing cells, the increase in cytosolic free Ca2+ induced by a proteinaceous elicitor, cryptogein, was greatly suppressed during the G2 and M phases in comparison with G1 or S phases. Treatment with cryptogein during the G1 or S phases also induced biphasic (rapid/transient and slow/prolonged) responses in activation of mitogen-activated protein kinases (MAPKs) and production of reactive oxygen species (ROS). In contrast, elicitor treatment during the G2 or M phases induced only a rapid and transient phase of MAPK activation and ROS production. Their slow and prolonged phases as well as expression of defense-related genes, cell cycle arrest and cell death were induced only after the cell cycle progressed to the G1 phase; removal of the elicitor before the start of the G1 phase inhibited these responses. These results suggest that although cryptogein recognition occurred at all phases of the cell cycle, the recognition during the S or G1 phases, but not at the G2 or M phases, induces the prolonged activation of MAPKs and the prolonged production of ROS, followed by cell cycle arrest, accumulation of defense-related gene transcripts and cell death. Elicitor signal transduction depends on the cell cycle and is regulated differently at each phase.

The molecular links between cell cycle control and the regulation of programmed cell death are largely unknown in plants. Here we studied the relationship between the cell cycle and elicitor-induced cell death using synchronized tobacco BY-2 cells. Flow cytometry and fluorescence microscopy of nuclear DNA, and RNA gel-blot analyses of cell cycle-related genes revealed that the proteinaceous elicitor cryptogein induced cell cycle arrest at the G1 or G2 phase before the induction of cell death. Furthermore, the patterns of cell death induction and defence-related genes were different in different phases of the cell cycle. Constitutive treatment with cryptogein induced cell cycle arrest and cell death at the G1 or G2 phase. With transient treatment for 2 h, cell cycle arrest and cell death were only induced by treatment with the elicitor during the S or G1 phase. By contrast, the elicitor-induced production of reactive oxygen species was observed during all phases of the cell cycle. These results indicate that although recognition of the elicitor signal is cell cycle-independent, the induction of cell cycle arrest and cell death depends on the phase of the cell cycle.

Inhibitory effects of extracts from peels of Citrus natsudaidai (natsumikan) encapsulated in hybrid liposomes (HL) composed of L-alpha-dimyristoylphosphatidylcholine and polyoxyethylene (20) sorbitan monolaurate on the growth of tumor cells were examined. The extracts with lower polar solvents inhibited the growth of B-16 mouse melanoma and human lung carcinoma cells, although the extracts with higher polar solvents showed no antitumor activity. In particular, the inhibitory effects of extracts with lower polar solvents encapsulated in HL were enhanced as compared with those of free extracts. Fluorescence microscopic analysis indicated that the HL including petroleum ether extracts induced apoptosis in B-16 mouse melanoma cells. On the other hand, the viability of normal human fibroblast cells was even less affected by the extracts of natsumikan. These results suggest that hydrophobic antitumor agents should be present in peels of natsumikan.

Ca(2+) is the pivotal second messenger for induction of defense responses induced by treatment of pathogen-derived elicitor or microbial infection in plants. However, molecular bases for elicitor-induced generation of Ca(2+) signals (Ca(2+) transients) are largely unknown. We here identified cDNAs for putative voltage-dependent Ca(2+)-permeable channels, NtTPC1A and NtTPC1B, that are homologous to TPC1 (two pore channel) from suspension-cultured tobacco BY-2 cells. NtTPC1s complemented the growth of a Saccharomyces cerevisiae mutant defective in CCH1, a putative Ca(2+) channel, in a low Ca(2+) medium, suggesting that both products permeate Ca(2+) through the plasma membrane. Cosuppression of NtTPC1s in apoaequorin-expressing BY-2 cells resulted in inhibition of rise in cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) in response to sucrose and a fungal elicitor cryptogein, while it did not affect hypoosmotic shock-induced [Ca(2+)](cyt) increase. Cosuppression of NtTPC1s also caused suppression of cryptogein-induced programmed cell death and defense-related gene expression. These results suggest that NtTPC1s are involved in Ca(2+) mobilization induced by the cryptogein and sucrose, and have crucial roles in cryptogein-induced signal transduction pathway.

Human neuroblastoma GOTO cell lines were established that stably express recombinant human lysosomal protective protein/cathepsin A (PPCA) cDNA by transfection. Intracellular cathepsin A (acid serine carboxypeptidase) activity increased four-fold compared with in those of the parent and mock-transfected cell lines. The immunoreactive 54 kDa precursor/zymogen and mature 32/20 kDa two-chain forms were produced in the cells. The amount of the latter form expressed in the GOTO cells was significantly larger than those in the PPCA-overexpressing CHO cell lines previously established. The intracellular proteins showed a typical lysosomal granular distribution and the glycosylated 54 kDa precursor was secreted into the culture medium without the addition of an alkalizing agent. The PPCA-overexpressing cell lines also retained the ability to differentiate bi-directionally as well as the parent cells; into neuronal cells on induction by dibutyryl cAMP in serum-free medium and into Schwannian cells on induction by bromodeoxyuridine. During the course of differentiation into neuronal and Schwannian cells, the intracellular cathepsin A activity further increased two and five times, respectively, which was associated with an increase in the expression of the 32/20 kDa two-chain form. The glycosylated precursor proteins were taken up via the mannose 6-phosphate receptors, and the cathepsin A, alpha-neuraminidase and beta-galactosidase (beta-Gal) activities deficient in the fibroblasts derived from a patient with PPCA deficiency (galactosialidosis) were restored. These results suggest that the bi-directional differentiation of GOTO cell lines stably expressing the recombinant human PPCA gene could be a model system for analyzing the functions of PPCA in peripheral neuronal cells and Schwannian cells as well as the recombinant PPCA could be a useful source for enzyme replacement therapy (ERT) for galactosialidosis patients.

The actions of peptidase inhibitors derived from Streptomycete on human cathepsin A (hCath A), yeast carboxypeptidase Y (CPY), and wheat carboxypeptidase II (CPW) were analyzed comparatively. Lactacystin and omuralide (clasto-lactacystin beta-lactone), well-known cytoplasmic proteasome inhibitors, both had a potent and non-competitive inhibitory effect on these homologous serine carboxypeptidases, although they inhibited CPW and hCath A more effectively than CPY in vitro. Ebelactone B exhibited a mixed non-competitive inhibitory effect and selectivity for CPY. Piperastatin A showed competitive inhibition of CPY and hCath A but had little effect on CPW. In contrast, chymostatin inhibited CPW efficiently, while it had less effect on hCath A and CPY. In cell culture system, lactacystin was the most potent as to inactivation of the intralysosomal recombinant hCath A activity expressed in a genetically engineered fibroblastic cell line with galactosialidosis (hCath A deficiency). These results suggest that the specific inhibitory effects of lactacystin and its derivatives on hCath A might be applicable to elucidate the pathophysiological roles in the human deficinecy.

We found a novel inhibitor specific to eukaryotic DNA polymerase epsilon(pol epsilon) from plant cultured cells, Nicotina tabacum L. The compound (compound 1) was a dipeptide alcohol, L-homoserylaminoethanol. The 50% inhibition of pol epsilon activity by the compound was 43.6 microg/mL, and it had almost no effect on the activities of the other eukaryotic DNA polymerases such as alpha, beta, gamma and delta, prokaryotic DNA polymerases, nor DNA metabolic enzymes such as human telomerase, human immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase, human DNA topoisomerase I and II, T4 polynucleotide kinase and bovine deoxyribonuclease I. Kinetic studies showed that inhibition of pol epsilon by the compound was non-competitive with respect to both template-primer DNA and nucleotide substrate. We succeeded in chemically synthesizing the stereoisomers, L-homoserylaminoethanol and D-homoserylaminoethanol, and found both were effective to the same extent. The IC(50) values of L- and D-homoserylaminoethanols for pol epsilon were 42.0 and 41.5 microg/mL, respectively. This represents the second discovery of a pol epsilon-specific inhibitor, and the first report on a water-soluble peptide-like compound as the inhibitor, which is required in biochemical studies of pol epsilon.

Ion fluxes and the production of reactive oxygen species (ROS) are early events that follow elicitor treatment or microbial infection. However, molecular mechanisms for these responses as well as their relationship have been controversial and still largely unknown. We here simultaneously monitored the temporal sequence of initial events at the plasma membrane in suspension-cultured tobacco cells (cell line BY-2) in response to a purified proteinaceous elicitor, cryptogein, which induced hypersensitive cell death. The elicitor induced transient rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) showing two distinct peaks, followed by biphasic (rapid/transient and slow/prolonged) Cl(-) efflux and H(+) influx. Pharmacological analyses suggested that the two phases of the [Ca(2+)](cyt) response correspond to Ca(2+) influx through the plasma membrane and an inositol 1,4,5-trisphophate-mediated release of Ca(2+) from intracellular Ca(2+) stores, respectively, and the [Ca(2+)](cyt) transients and the Cl(-) efflux were mutually dependent events regulated by protein phosphorylation. The elicitor also induced production of ROS including (*)O(2)(-) and H(2)O(2), which initiated after the [Ca(2+)](cyt) rise and required Ca(2+) influx, Cl(-) efflux and protein phosphorylation. An inhibitor of NADPH oxidase, diphenylene iodonium, completely inhibited the elicitor-induced production of (*)O(2)(-) and H(2)O(2), but did not affect the [Ca(2+)](cyt) transients. These results suggest that cryptogein-induced plasma membrane Ca(2+) influx is independent of ROS, and NADPH oxidase dependent ROS production is regulated by these series of ion fluxes.

Background and Purpose: Thymectomy is generally accepted as the major option of treatment for myasthenia gravis. To elucidate the biological role of thymectomy in the treatment of myasthenia gravis, the immunologic characteristics of the thymus was studied in association with the postoperative kinetics of the anti-acetylcholine receptor antibody titer., Materials and Methods: Thirty-four patients with nonthymomatous myasthenia gravis who had positive anti-acetylcholine receptor antibody titer and undergoing extended thymectomy were subjected to the study. Reduction of anti-acetylcholine receptor antibody titer was evaluated in terms of the proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy to that before the operation. The numbers of B lymphocytes (CD19(+) cells) and the germinal center B lymphocytes (CD19(+)CD38(high) cells) present in 1 g of the thymic tissue were calculated by flow cytometry., Results: The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy ranged from 27.5% to 150%. The numbers of B lymphocytes and the germinal center B lymphocytes in 1 g of the thymic tissue ranged from 0.19 x 10(6)/g to 162.8 x 10(6)/g and from 0.09 x 10(6)/g to 33.4 x 10(6)/g, respectively. The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy had a significant inverted correlation with the number of B lymphocytes (P =.002) as well as that of the germinal center B lymphocytes (P =.007)., Conclusion: Effectiveness of thymectomy was dependent on predominance of B lymphocytes and the germinal center B lymphocytes in the thymus, suggesting that one of the biological roles of thymectomy in the treatment of myasthenia gravis is removing the thymus-associated germinal centers.

Unlabelled: The objective of our study is to determine whether 67Ga SPECT can supplement CT and/or MRI diagnostic information by visual comparison of the two separate data sets in patients with head and neck tumors., Methods: A total of 50 patients with head and neck tumors (benign: 19, malignant: 31) were entered in the study. Three board-certified radiologists who had practical experience in interpreting both head and neck CT/MRI and 67Ga SPECT images, participated as readers. All of the CT and/or MR images of each patient were shown to each reader first, who after they had finished interpreting them were shown the 67Ga SPECT images. They were asked to score each image on a 7-point scale for the likelihood of the presence or absence of malignancy. Histological or cytological evaluation was done in all cases, and the radiologic studies were correlated with these findings., Results: Improvement of all three readers' performance was from 70.7% to 83.3% in the mean accuracy and from 0.790 to 0.921 in the mean Az value (p = 0.033, 0.163, 0.105 in the Az values) after they were shown the 67Ga SPECT images., Conclusions: 67Ga SPECT should substantially increase confidence in the diagnosis of head and neck tumors when CT and/or MRI do not permit differentiation between benign and malignant disease.

Unlabelled: Using precision-cut liver slices (20-25 mg wet weight) from male Wistar rats, we examined whether clinically relevant propofol concentrations have hepatoprotective or -toxic effects during hypoxia/reoxygenation. Slices were preincubated for 2 h in sealed roller vials (three slices per vial) containing Waymouth's medium (37 degrees C; 95% oxygen/5% CO(2)). Then, propofol or Intralipid was added to create four different groups (control, Intralipid, small-concentration propofol [0.5-1.5 micro g/mL], and large-concentration propofol [2.0-6.0 micro g/mL]). Thereafter, each group was incubated for 4 h under 95% oxygen/5% CO(2) (no hypoxia) or for 2 h under 100% nitrogen plus 2 h under 95% oxygen/5% CO(2) (hypoxia/reoxygenation). Slice viability and hypoxia/reoxygenation injury were assessed at 2, 3, and 4 h after incubation began by using the slice intracellular K(+) concentration, energy status (adenosine triphosphate content, total adenine nucleotides content, and energy charge), and liver enzyme leakage (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). Propofol and Intralipid caused a significant delay in energy charge recovery in comparison with the control. There were no significant differences between the propofol groups and the other two groups in intracellular K(+) content or liver enzyme leakage. Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury., Implications: Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury.

Process extension is a most marked and characteristic neuronal feature that is observed during the development, regeneration and plasticity of nervous system tissues. Neuro-p24, a novel membranous protein with a molecular weight of 24 kDa, is specifically localized in neurons, particularly in the neurites. Based on its molecular structure and distribution pattern in the brain we proposed that Neuro-p24 plays a role in neurite extension. In the present study we have made several findings that support this hypothesis; first, Neuro-p24 was abundant in motor axonal fibers, neurites of dorsal root ganglia neurons and apical dendrites of cerebral cortex neurons when their extension or arborization was proceeding very actively. Secondly, when COS-7 epithelial cells were transfected with either wild-type or deletion-mutated Neuro-p24 cDNAs, ectopic expression of wild-type cDNA caused morphological alterations resulting in a neuron-like appearance. These observations firmly support our proposal and indicate that Neuro-p24 plays an important role in the nervous tissue.

CD45 molecules are known to appear as various isoforms generated by alternative splicing of variable exons 4, 5, and 6, but the detailed profile of CD45 isoform expression during thymocyte development has not been revealed. We examined the CD45 isoforms expressed in the various human thymocytes' subsets defined by CD3, CD4, and CD8 expressions using RT-PCR and 4-color flow cytometry. RT-PCR study revealed that RABC, RAB, RBC, RB, and R0 isoforms were expressed in thymocytes while any of RAC, RA, or RC isoforms were not detected. RABC, RAB and RBC isoforms were expressed at CD3(-)CD4(-)CD8(-) and CD3(+)CD4(+)CD8(-) stages, but were barely detectable at CD3(-)CD4(+)CD8(+) stage. RB isoform was consistently expressed at a relatively high level at all stages. R0 isoform was expressed at a low level at CD3(-)CD4(-)CD8(-) and CD3(-)CD4(+)CD8(-) stages but upregulated at CD3(+)CD4(+)CD8(+) and CD3(+)CD4(+)CD8(-) stages. In combination with the results obtained by 4-color flow cytometric study, CD45 isoform expression on human thymocytes were determined to be RABC(+)RAB(+/-)RBC(+)RB(+)R0(+/-) at CD3(-)CD4(-)CD8(-) stage, RABC(-)RAB(-)RBC(-)RB(+)R0(+) at CD3(-)CD4(+)CD8(-) and CD3(-)CD4(+)CD8(+) stages, RABC(+/-)RAB(+)RBC(+)RB(++)R0(++) at CD3(+)CD4(+)CD8(+) stage, and RABC(+)RAB(+)RBC(+)RB(++)R0(+) at CD3(+)CD4(+)CD8(-) stage. Bcl-2 expression was upregulated between CD3(-)CD4(+)CD8(+)CD45R0(+) and CD3(+)CD4(+)CD8(+)CD45R0(+) stages. Expression of CD45R0 epitope was upregulated between CD3(-)CD4(+)CD8(+)CD69(-) and CD3(+)CD4(+)CD8(+)CD69(+) stages while CD45RA epitope expression was unchanged. Thus, when thymocytes are positively selected, CD45R0 isoform expression seems to be upregulated while CD45RABC isoform expression stays at a very low level. In summary, various isoforms of CD45 were shown to be tightly regulated during thymocyte development and through the selection process.

We herein describe the MRI findings in a patient clinically diagnosed with primary Sjögren's syndrome (SjS) initially manifested by retrobulbar optic neuritis. A 63-year-old woman suddenly had left ocular pain and progressive visual disturbance. MR T2-weighted images revealed hyperintensity in the left optic nerve, with swelling. Contrast-enhanced T1-weighted images showed no abnormal enhancement. Follow-up MRI 6 months after admission revealed no significant changes in the affected optic nerve. To our knowledge, optic neuritis as a complication of SjS has been reported in ten patients [1, 2, 3, 4, 5, 6] and MRI findings in only one of them [6]. We thought MR images were useful for visualizing optic nerve involvement in SjS and observing its course.

Purpose: Sevoflurane and isoflurane have been reported to exert protective effects against ischemia-reperfusion injury (IRI) in various organs. To compare the effect of sevoflurane anesthesia on liver IRI with that of isoflurane anesthesia, we performed the present study in pigs., Methods: Nineteen pigs were assigned to either the sevoflurane ( n = 9) or the isoflurane group ( n = 10). Hepatic warm ischemia was produced by 30-min hepatic artery and portal vein clamping beginning 90 min after the start of the inhalation anesthesia; this was followed by a 240-min reperfusion. To extend our evaluation, we evaluated the degree of IRI using various parameters (plasma alpha-glutathione-S-transferase [alpha-GST], lipid peroxide, and lactate concentrations), in addition to the conventionally used liver damage markers., Results: The lactate level was significantly higher under isoflurane than under sevoflurane at 120 min after reperfusion (4.0 +/- 0.4 mmol.l(-1) vs 2.5 +/- 0.3 mmol.l(-1); P < 0.05). How-ever, this difference had disappeared after 240 min of reperfusion. No significant differences between the two groups were observed in values for alpha-GST, lipid peroxides, aspartate aminotransferase, alanine aminotransferase, or lactic dehydrogenase., Conclusion: The extent of the hepatic IRI seen under sevoflurane anesthesia in pigs did not differ significantly from that seen under isoflurane, as judged from measurements of a number of parameters over a 240-min reperfusion period.

Background: Anterior mediastinal masses derive from a variety of diseases. Thymomas have been shown to commonly hold CD4(+)CD8(+) double-positive (DP) lymphocytes, and identification of this subset by two-color flow cytometric study was suggested to help diagnosis of thymoma. Several other thymic diseases, however, possibly hold CD4(+)CD8(+) DP lymphocytes. In this study, we utilized the three-color flow cytometric method for further examination of the phenotypes of lymphocytes in the thymic diseases., Materials and Methods: One hundred eight specimens (77 primary and 10 metastatic thymomas, 10 thymic carcinomas, 2 thymic carcinoids, 4 malignant lymphomas, 2 seminomas, an inflammatory pseudotumor, and 2 nonneoplastic thymic hyperplasias) were subjected to the study. The expressions of CD3, CD4, and CD8 on tumor-associated lymphocytes were evaluated by three-color flow cytometric study., Results: The proportion of the CD4(+)CD8(+) DP subset was more than 30% in all 78 lymphocyte-rich thymomas, in 2 malignant lymphomas, and in both thymic hyperplasias. CD3 expression of the CD4(+)CD8(+) DP subset ranged from a negative to a high level in thymomas and thymic hyperplasias, while it was restricted to a particular level in CD4(+)CD8(+) DP-type malignant lymphomas. The proportion of CD3(+) cells in the CD4(+)CD8(-) single-positive subset was consistently less than 90% in the lymphocyte-rich thymomas, while it was more than 90% in the thymic hyperplasias., Conclusion: Although identification of the CD4(+)CD8(+) DP subset in the tumor-associated lymphocytes does not necessarily indicate thymoma, a further characterization of thymic neoplasms possessing the CD4(+)CD8(+) DP subset was enabled by three-color flow cytometric study, suggesting the utility of this method as an ancillary tool for differential diagnosis of these diseases.

A 38-year-old female with systemic lupus erythematosus (SLE), myasthenia gravis (MG), and pemphigus foliaceous (PF) was scheduled to undergo total hysterectomy and lymphadenectomy. Preanesthetic examination revealed anemia, a prolonged activated partial thromboplastin time, and a reduced percent vital capacity. Antiphospholipid antibody was not positive. After treating the bullous lesions of PF and the muscle weakness due to MG (noted on admission for surgery) with oral prednisolone, the patient was scheduled for surgery. To avoid the use of a muscle relaxant and the potential complications of the airway manipulation involved in using a laryngeal mask or endotracheal tube, since the patient had MG and PF, a regional anesthetic technique was selected. This involved continuous epidural anesthesia, achieved using 1% or 2% mepivacaine, with sedation by a combination of propofol infusion (3 mg.kg-1.hr-1) and nitrous oxide (60% in oxygen). The patient breathed spontaneously under the mask throughout the 3.5-hr operation. The intraoperative surgical and anesthetic course was uneventful. After a benign postoperative course, the patient was discharged on the 16th postoperative day.

The Dyggve-Melchior-Clausen syndrome (DMCS) is a rare autosomal recessive skeletal dysplasia characterized by short-trunk dwarfism and mental retardation. A 49-year-old male with DMCS underwent resection arthroplasty for contracture of the right hip joint under general anesthesia using thiamylal, nitrous oxide, sevoflurane, and vecuronium. Although he was assumed to have difficult airway due to short neck, macroglossia, and disturbance of neck flexion, tracheal intubation was not difficult. No complications including malignant hyperthermia were observed during the 95 min of the operation.

We examined the clinical and functional significance of histologic classification of thymic epithelial neoplasms proposed by the World Health Organization (WHO), based on an analysis of 146 consecutive tumors derived from 141 patients and 47 normal thymuses derived from children ranging in age from 1 to 9 years. Invasive tumors were seen in 12.5%, 38.6%, 40.0%, 69.4%, 80.0%, and 100% of type A, AB, B1, B2, B3, and C primary tumors, respectively. All of six recurrent or metastatic lesions were type B2 tumors. Myasthenia gravis was associated in 0%, 6.8%, 40.0%, 55.6%, 10.0%, and 0% in patients with type A, AB, B1, B2, B3, and C tumors, respectively. The average number (x10(6)) of tumor-associated CD4+CD8+ cells present in 1 g of tumor tissue was 1.5, 391.1, 1041.7, 333.9, 24.5, and 0.2 in type A, AB, B1, B2, B3, and C, respectively, and it was 1168.2 in the normal thymuses. Thus, type B1 tumor retained the function to induce CD4+CD8+ double-positive cells at a level comparable to that of the normal thymic cortical epithelial cells, followed by type AB and type B2 tumors. Type A and B3 tumors had this function at a barely detectable level, and type C tumor was nonfunctional. WHO histologic classification was shown to reflect the clinical features and the T-cell-inducing function of thymic epithelial tumors.

Thymoma is known to contain CD4+CD8+ T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4+ T cell development in thymoma and that IFN-gamma-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-gamma-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-gamma in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3+ cells in the CD4+CD8- subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-gamma. These results indicate that impaired up-regulation of HLA-DR in response to IFN-gamma results from insufficient induction of CIITA, but not from the signal from IFN-gamma receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4+ T cell development in thymoma.

A 27-year-old woman (38 week pregnant) was admitted to an obstetric hospital with an acute severe abdominal pain. At that time, the fetal heart sound was not audible. The diagnosis of placental abruption was made and she underwent an emergency cesarean section (C/S) under general anesthesia. She had anemia which became worse in the first few hours after C/S, requiring blood transfusion. ST depression was also present in the ECG during this period. Subsequently, we found an increase in myocin light chain, but not in troponin-T. On the 2nd postoperative day, pulmonary edema appeared and DIC was suspected. We treated her with nitrates, diuretics, protease inhibitors and oxygen by mask. She was discharged on 14th postoperative day with no other complications. Cardiac echogram showed no abnormalities, but a borderline change was seen in her exercise ECG. Depression of the ST segment has been reported in C/S patients, but this does not indicate myocardial ischemia (MI) nor treatment is necessary in most cases. In our case, the diagnosis was not conclusive, but in view of the risks associated with MI, patients with placental abruption should be managed strictly as if they have MI.

A 33-year-old male presented with involuntary and inappropriate laughter. Neuroimaging revealed a meningioma ventrolateral to the pons and midbrain, attached to the medial middle tentorium on the left side. The pathological laughter ceased immediately after subtotal removal of the tumor. Pathological laughter may be an early focal sign of a mass compressing ventrolateral brainstem.

A human thymoma is a neoplasm derived from the thymic epithelial cell, and is well known for its association with autoimmune diseases, especially myasthenia gravis. The neoplastic epithelial cells of thymoma clearly retain thymic epithelial functions, but the development of T cells in thymoma is somewhat impaired. In this study, we quantified by flow cytometry the in vitro expression of MHC molecules on neoplastic epithelial cells precultured with IFN-gamma. While MHC class I expression was comparable with that on normal thymic epithelial cells, the level of MHC class II molecules on neoplastic epithelial cells was lower than in controls, and also varied greatly from case to case. Additionally, there was a significant positive correlation between the expression level of MHC class II and the proportion of mature CD3+ cells in the CD4+CD8- subset. Thus, accumulation of CD3-CD4+CD8- cells in thymoma may result from impaired expression of the MHC class II molecules, suggesting that the function of the neoplastic epithelial cells might determine the maturation and the positively selected repertoire of T cells in thymomas.

A 70-year-old male with renal cell carcinoma extending into the retrohepatic inferior vena cava was scheduled for radical nephrectomy with vena caval resection under general anesthesia. He had received partial gastrectomy for gastric cancer twelve years before. Computed tomography and inferior vena cavography confirmed that the vena cava was almost completely occluded and that a collateral venous network was well established. It was considered that the surgical approach to the retrohepatic cavals area was technically very difficult, and that there was a high possibility of a pulmonary embolus during the surgical manipulation. To prevent a pulmonary embolus and get good control of the vena cava above the tumor and below the hepatic vein, we decided to use a partial cardiopulmonary bypass (CPB) until the vena cava was clamping above the tumor. Anesthesia was induced with propofol and fentanyl, and maintained with fentanyl and isoflurane-N2O-O2. In the partial CPB blood from the hepatic vein was drained from the inferior vena cava cannula through right atrium, oxygenated by microporus membrane oxygenator, and returned to the left femoral artery. Cannulation to drain the venous circulation entering the vena cava below the tumor was abandoned because the extensive collateral venous network ultimately drains into the superior vena cava. The partial CPB time was 90 min, and the bladder temperature during the CPB was 35-36 degrees C. During the 7.3 hr procedure, the pulmonary embolus did not occur and the total blood loss was 5515 ml. The patient made an uncomplicated recovery and was discharged 30 days after the operation. This newly reported partial-CPB method may be safe and effective for the management under anesthesia of other patients.

Human thymoma is derived from thymic epithelial cells and often associated with a large number of cortical thymocytes. Since thymic epithelial cells play key roles in T-cell development in the normal thymus, we hypothesized that the neoplastic epithelial cells of thymoma may support T-cell differentiation. We attempted to reconstitute the T-cell development in vitro by using neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on a proportion of CD4-CD8- cells in thymoma. These CD34+CD4-CD8- cells also expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. The CD34+CD4-CD8- cells purified from a normal thymus also differentiated to CD4+CD8+ cells in an allogeneic co-culture with the neoplastic epithelial cells of thymoma. In addition, a pleural dissemination from thymoma contained a large amount of cortical thymocytes. These results suggest that the neoplastic epithelial cells retain the function of thymic epithelium and can support T-cell development in thymomas.

A 33-year-old male was scheduled for tonsillectomy and pharyngoplasty due to sleep apnea syndrome. The intubation was uneventful following induction with thiamylal and vecuronium. Anesthesia was maintained with O2-N2O-sevoflurane. No complications were observed during the 90 min operation. After the termination of the anesthesia, a hyperadrenergic state was observed: arterial pressure and heart rate rose to 230/135 mmHg and 135 bpm, respectively. Immediately after extubation, he developed dyspnea with tracheal tag and stridor, and became cyanotic despite the use of a simple oxygen mask and assisted ventilation. Laryngospasm was suspected. The patient was reintubated and suctioned; pink, frothy sputum was not obtained. Arterial blood gases 5 minutes after reintubation revealed a pH of 7.24, Pao2 86 mmHg (FIo2 1.0), and Paco2 54 mmHg. Chest X-ray 30 minutes after reintubation revealed bilateral diffuse alveolar infiltration. The diagnosis was interstitial pulmonary edema. The patient was ventilated mechanically by applying a positive end-expiratory pressure of 5cm H2O, and furosemide and dopamine were administered intravenously. The patient was extubated the next day, and discharged from hospital ten days later. We considered that the lung edema was induced by the severe negative pressure generated by inspirating against a closed upper airway, as well as by the hyperadrenergic state and severe hypoxemia observed during and after extubation.

Thymoma is a thymic epithelial tumor which often contains a large number of immature T cells. Although the metastatic lesions are also associated with abundant lymphocytes, their characteristics have not been assessed in detail. In this study, the phenotype was analyzed and compared with those in their primary lesions. Nine metastatic thymomas were obtained from seven patients. In the metastatic lesions, CD1a+ cells and CD4(+)CD8(+) cells accounted for 77.7 +/- 10.6 and 52.3 +/- 15.8% of all the lymphocytes, respectively. In five primary lesions and their metastatic lesions, CD3(-)CD4(+)CD8(-) cells accounted for 23.9 +/- 16.9 and 45.2 +/- 15. 5% of the CD4(+)CD8(-) cells, respectively. CD69 was expressed on 70. 9 +/- 9.5 and 53.1 +/- 11.8% of the CD4(+)CD8(-) cells, respectively. These results indicate that the metastatic lesions of thymoma are associated with abundant immature T cells which are phenotypically less mature than those in their primary lesions., (Copyright 1998 Academic Press.)

In patients with bilateral vocal cord paralysis, several therapeutic techniques have been proposed to improve laryngeal obstruction. Since 1990, we have performed Ejnell's operation on six patients, one male and five females, suffering from bilateral vocal cord paralysis. Tracheostomy had been performed in four patients prior to their consultation. Five patients underwent a breathing capacity examination before and after the operation. Four of the patients showed improvement in breathing capacity and the tracheostoma was closed in those four patients. There was little aspiration problem during the postoperative follow-up period. Our experience suggests that Ejnell's operation is technically simple and should be useful in the treatment of bilateral vocal cord paralysis.

Objectives: To quantitatively evaluate the effect of vocal fold lengthening on pliability of the mucosa measured along the superior-inferior axis and to examine the relation of the location of mucosal upheaval (MU) during phonation to the changes in pliability pattern of the mucosa when the vocal fold was lengthened., Design: Investigation of mechanical characteristics of the vocal fold in relation to the MU during phonation., Materials: Five excised canine larynges., Interventions: Vibrations with and without vocal fold lengthening were recorded from the tracheal side via high-speed photography or video recording combined with stroboscopic illumination. Tattooed marks on the lower surface of the vocal fold were used to locate the MU. Pliability was defined as the maximal distance elevated in response to a constant focal negative pressure., Results: Pliability decreased significantly (P=.05) when the vocal fold was lengthened. The point of minimal pliability and MU without vocal fold lengthening were located slightly above the area where the muscular layer approached the epithelial layer. They were located closer to the free edge of the vocal fold when it was lengthened than when it was not. Discrepancy of their locations when the vocal fold was lengthened was suggested., Conclusions: The MU occurs around the point of minimal pliability when the vocal fold is not lengthened, whereas the MU occurs slightly more laterally than the point of minimal pliability when the vocal fold is lengthened. Although further study is necessary to explain this discrepancy, the presence of the sparse deep layer of the lamina propria seems to be essential in the generation of the mucosal wave.

The movement characteristics of mucosal waves of the vocal fold are important components in normal phonation. Quantitative studies of the mucosal wave have used stroboscopic techniques from a supraglottic view. The current study measured displacement of mucosal epithelium during experimental phonation by using high-speed photography from an infraglottic view. Effects of thyroarytenoid contraction, increased mean airflow rate, and variation of vocal fold length were examined in canine larynges. Top and bottom vocal fold "lip" amplitude, fundamental frequency, and phase difference were the dependent variables examined. Thyroarytenoid contraction increased the amplitude of the top and bottom lips, decreased the fundamental frequency, and increased the phase difference. Increase in airflow through the glottis decreased the top lip amplitude and phase difference and appeared to increase the fundamental frequency and to decrease the bottom lip amplitude. Vocal fold lengthening decreased the bottom lip amplitude and increased the fundamental frequency and appeared to decrease the top lip amplitude and phase difference.

Subglottic stenosis as a complication of Wegener's granulomatosis (WG) is a relatively rare lesion and is difficult to treat surgically once stenosis becomes sufficiently severe to cause inspiratory dyspnea. Thus, it is important to diagnose WG in its early stages to prevent troublesome subglottic stenosis from developing by initiating immunosuppressive therapy. The authors report on a 30-year-old woman suffering from subglottic stenosis of sudden onset due to protracted WG limited to the head and neck region. She had had exudative otitis media for 13 years and saddle nose and nasal crusting for five years. Repeated biopsies of the nasal mucosa and enzyme-linked immunosorbent assays for cytoplasmic patterns of antineutrophil cytoplasmic autoantibody (cANCA) had failed to establish the diagnosis. However, further histologic examination of the nasal mucosa showed vasculitis, and indirect immunofluorescence detected the presence of cANCA. Thus, the diagnosis of WG was confirmed 13 years after the appearance of the initial symptoms in the ear. The patient was given prednisolone (60 mg/day for five days), which greatly relieved the subglottic stenosis. The prednisolone dosage was then tapered to 5 mg/day.

We investigated the effects of two different concentrations of sevoflurane, 0.4 minimum alveolar anesthetic concentration (MAC) and 1.0 MAC, on insulin secretion before, during, and after sevoflurane anesthesia using three successive intravenous glucose tolerance tests (IVGTT) in pigs with indwelling catheters. We also investigated changes in the levels of plasma glucose, catecholamines (epinephrine [E], norepinephrine [NE]), and cortisol (Cor). The pigs were grouped as awake, 0.4 MAC, or 1.0 MAC. Sevoflurane decreased the ratio of insulin/glucose (INS/GLU) in the basal condition (P < 0.05 awake versus 1.0 MAC) and during IVGTT (P < 0.01 awake versus 1.0 MAC and 0.4 MAC). These decreases were quickly reversible (control levels were regained within 2 h of the end of anesthesia), were probably dose-related, appeared not to be mediated by E, NE, or Cor. In addition, the INS/GLU ratio 2.5-4 h after the end of anesthesia was significantly higher in the anesthetized groups than in the awake group. We conclude that sevoflurane anesthesia has a rapidly reversible inhibitory effect on basal and glucose-stimulated insulin secretion, as do other inhaled anesthetics, and might induce insulin resistance.

We report here cloning of the cDNA of a novel membrane protein, termed p24, which, of the eight mouse tissues tested, was found only in brain where it is localized exclusively in neurons. The cDNA encodes 196 amino acids with a molecular weight of approximately 24000. P24 contains two putative membrane spanning domains and a sequence in the hydrophilic tail homologous to the microtubule-binding domain of microtubule-associated proteins, such as TAU and MAP-2. We prepared antibodies to p24 and demonstrated that the protein is rich in nerve fibers of the cerebral cortex, anterior cerebral nuclei and hypothalamus. When neuroblastoma Neuro 2a cells were treated with retinoic acid to induce differentiation, p24 mRNA increased but the p24 protein was not detected. The protein expressed from the p24 cDNA in non-neuronal Cos-7 cells was 24 kDa in size and were localized only in lysosomes. These findings indicate that p24 is a neuron-specific membrane protein localized in intracellular organelles of highly differentiated neural cells and suggest that it may play a role in the neural organelle transport system.

Stiffness of the vocal fold is a significant factor in determining mucosal wave propagation and in the control of the fundamental frequency of phonation. We measured pliability of the vocal fold mucosa in an in vivo canine model as an index of stiffness while the histological layer-by-layer structure of the vocal fold was not disrupted. The point 1 mm below the free edge showed a maximal pliability that gradually diminished toward the tracheal side and reached a minimum. When the thyroarytenoid (TA) muscle contracted, pliability of the mucosa was significantly increased (P < 0.001). Mucosal pliability of the excised larynx was significantly increased compared with that in vivo (P < 0.001). The point of minimal pliability in the absence of TA muscle contraction did not shift after excision of the larynx, while TA muscle contraction caused a downward shift of the point of minimal pliability. Mucosal pliability can thus be used to quantitatively assess the effects of TA muscle contraction on stiffness of the vocal fold mucosa.

The mucosal upheaval where the mucosal wave starts and propagates upward appears on the lower surface of the canine vocal fold during vibration. We investigated the vibratory behavior of the in vivo human vocal fold viewed from the tracheal side. Subjects consisted of 14 men and 6 women who had undergone tracheostomy for various head and neck diseases; their ages ranged from 22 to 70 years, with a mean of 53.9 years. The inferior aspect of the vocal fold during phonation was observed with the aid of a rigid oblique-view endoscope inserted through a tracheostoma (inferior glottoscopy). Each subject was asked to sustain the vowel /a/ at a comfortable pitch and loudness (easy phonation) and then at a higher pitch. Inferior glottoscopy could be performed during easy phonation in 19 subjects and during high-pitched phonation in 10 subjects. During easy phonation, the mucosal upheaval appeared on the lower surface of the vocal fold between the anterior commissure and the vocal process in all 19 subjects. During high-pitched phonation, the vocal fold became longer, and the subglottic vault surrounded by the bilateral mucosal upheavals became narrower compared with those during easy phonation. Use of a dilated blood vessel as a landmark in one subject showed the location of the mucosal upheaval on the vocal fold mucosa to actually shift medially toward the oral side during high-pitched phonation. Despite structural differences between the human and canine vocal folds, the infraglottic aspect of the vocal fold vibration observed in the living human larynx was quite similar to that observed in the excised canine larynx.

A 3-year-old boy presented with an unusual consciousness disturbance accompanied by involuntary movement disorder after radical surgical removal of a huge hypothalamic glioma. Postoperative computed tomography and magnetic resonance imaging revealed a lesion in the bilateral basal ganglia. Marked neurological improvement was obtained by treatment with dopamine agonists, suggesting that the disruption of the dopaminergic pathway via the hypothalamus was the cause of these neurological symptoms.