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Background: This work aimed to examine the predictive value for death of various clinical variables after long-term hemodialysis (HD)., Design, Setting, Participants, and Measurements: A total of 947 patients (597 men and 350 women, aged 21 to 93 yr) who were undergoing maintenance HD in Niigata, Japan, were stratified into two cohorts: Those with >10 yr of prior HD at study enrollment (n = 391) and those with < or =10 yr of previous therapy (n = 556). The survival of patients was examined for up to 40 mo (1999 to 2003) with the Cox proportional hazards model. Baseline clinical and dialysis data and serum biochemistries were used as independent variables. For adjustment for bias in patient selection, patient survival in either cohort was analyzed separately., Results: In patients with >10 yr of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality risk predictors, whereas for those with < or =10 yr of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were NS predictors in those with long-term HD., Conclusions: Providing adequate dosage of dialysis and achieving a better control of pulse pressure may further improve survival in selected patients who had undergone HD for >10 yr.

Injury to the spinal nerves of mice induces allodynia and hyperalgesia. Intrathecal injection of the progesterone/estrogen receptor antagonist ICI 182,780 produced antinociceptive effects. Co-administration of estrogen did not reduce but tended to enhance the antinociceptive effect of ICI 182,780. On the other hand, co-administration of progesterone dose-dependently reduced the antinociceptive effect of ICI 182,780, indicating that the antinociceptive effect is through antiprogesterone receptor activity of ICI 182,780. These results suggest that spinal progesterone receptors play an important role in neuropathic pain, and that controlling the activity of progesterone receptors may be of great importance in the treatment of neuropathic pain.

Background: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet., Methods: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene., Results: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype., Conclusions: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

Background: The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARalpha on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model., Methods: The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells., Results: Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats., Conclusion: BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis.

Background: Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown., Methods: We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated., Results: In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells., Conclusion: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.

We have established a novel preadipocyte cell line from mouse adult mature adipocytes. The mature adipocytes were isolated from fat tissues by taking only the floating population of mature fat cells. The isolated mature adipocytes were de-differentiated into fibroblast-like cells. The in vitro studies showed that the cells could re-differentiate into mature adipocytes after over 20 passages. The in vivo transplantation study also demonstrated that the cells had the full potential to differentiate into mature adipocytes, which has not been shown for the 3T3-L1 preadipocyte cell line derived from mouse embryo. We have further analyzed the expression profile of key fat regulatory genes such as the peroxisome proliferator-activated receptorgamma or CCAAT/enhancer-binding protein gene families. We conclude that our cell line could be used as a preferred alternative to 3T3-L1, potentially reflecting the characteristics of mature adipocytes more, since the cell line is actually derived from adult mature adipocytes.

Background: Amyloid light-chain (AL)-type amyloidosis is a plasma cell disorder with a poor prognosis for survival. Although prognostic factors, such as the number of organs involved and heart function or failure in respond to therapy have been clarified based on studies including a large series of patients, there are large interindividual differences in the prognosis of patients with primary AL-type renal amyloidosis., Methods: To clarify the prognostic factors of AL-type renal amyloidosis, we retrospectively investigated the clinical manifestations, histopathological data, and prognosis of 21 patients with amyloidosis, who had been diagnosed by renal biopsy., Results: Eleven patients died, at a mean observational time of 21.7 months after renal biopsy, whereas the mean observational time was 51.0 months for the 10 patients who survived. The creatinine clearance rate was significantly higher, and the serum creatinine concentration and the grade of interstitial damage were significantly lower in surviving patients (P < 0.05). The presence of amyloid fibrils in organs other than the kidney did not influence prognosis for survival. However, the intraventricular septum was thinner in surviving patients (P < 0.1). Thirteen patients had undergone melphalan-prednisolone therapy, but it did not affect prognosis for survival. Cox proportional hazard regression analysis revealed that the renal function at the time of diagnosis was a significant and independent prognostic factor for survival., Conclusions: Our study demonstrated that renal function at the time of biopsy and renal interstitial damage are the best predictors of survival in AL-type renal amyloidosis.

In the reoxidative refolding of Streptomyces griseus trypsin, which is a serine protease having three S-S bonds per molecule, a synthetic inhibitor immobilized on agarose beads was applied in order to avoid the digestion of non-renatured protease molecules by renatured ones. A semi-continuous refolding system was fabricated by packing such inhibitor-immobilized gels in a glass column and the optimal operating conditions were investigated. Taking account of the effective conditions surveyed in the system, a continuous refolding system was constructed and operated to achieve higher performance. By application of the continuous system, a marked increase in the recovery rate as well as high recovered activity could be accomplished, i.e., the recovery rate obtained was ca. 40 times higher than that in the semi-continuous system. This system was also revealed to be substantially advantageous since it includes not only effective refolding but also separation, purification and enrichment processes in one operation.

An aldehyde oxidase, which oxidizes various aliphatic and aromatic aldehydes using O(2) as an electron acceptor, was purified from the cell-free extracts of Pseudomonas sp. KY 4690, a soil isolate, to an electrophoretically homogeneous state. The purified enzyme had a molecular mass of 132 kDa and consisted of three non-identical subunits with molecular masses of 88, 39, and 18 kDa. The absorption spectrum of the purified enzyme showed characteristics of an enzyme belonging to the xanthine oxidase family. The enzyme contained 0.89 mol of flavin adenine dinucleotide, 1.0 mol of molybdenum, 3.6 mol of acid-labile sulfur, and 0.90 mol of 5'-CMP per mol of enzyme protein, on the basis of its molecular mass of 145 kDa. Molecular oxygen served as the sole electron acceptor. These results suggest that aldehyde oxidase from Pseudomonas sp. KY 4690 is a new member of the xanthine oxidase family and might contain 1 mol of molybdenum-molybdpterin-cytosine dinucleotide, 1 mol of flavin adenine dinucleotide, and 2 mol of [2Fe-2S] clusters per mol of enzyme protein. The enzyme showed high reaction rates toward various aliphatic and aromatic aldehydes and high thermostability.

An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi2=6.062, P=0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P=0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P=0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.

Background: Blockade of the renin-angiotensin system (RAS) is well documented to be renoprotective; however, not all patients with glomerulonephritis respond well to this therapy. The interindividual variation in response to the RAS blockade may be in part genetically determined, whereas the results have been controversial., Methods: We investigated whether the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker on renal prognosis is modified by the angiotensinogen gene (AGT) polymorphism in immunoglobulin A nephropathy (IgAN). In total, 259 patients with histologically proven IgAN were analyzed for clinical manifestations, renal survival, and their associations with AGT A(-20)C and M235T., Results: The renal prognosis of 110 patients, who received ACE inhibitors/angiotensin receptor blocker during their clinical course, was significantly better than those without ACE inhibitors/angiotensin receptor blockers despite higher blood pressures and heavier proteinuria. The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 1.0 g/day) of 3.346 (P = 0.0001), hypertension of 1.949 (P = 0.01), deteriorated renal function of 3.040 (P < 0.0001), no ACE inhibitor/angiotensin receptor blocker administration of 2.725 (P = 0.0004), and the T235 and C(-20) haplotype of 1.608 (P = 0.0322). Only in patients carrying at least one M235 and A(-20) haplotype did the administration of ACE inhibitors/angiotensin receptor blockers have no significant effect on the prognosis of renal function (Kaplan-Meier, log rank test, chi2 = 0.700; P = 0.4028), whereas it was significant in patients who had other haplotypes of AGT (chi2 = 11.805; P = 0.0006)., Conclusion: This study provides evidence that the M235T and A(-20)C genotype of AGT can influence the therapeutic efficacy of a RAS blockade on the renal survival in IgAN.

Background: Few reports have been published regarding peripheral lung adenocarcinomas that are 10 mm or less in diameter. This is considered to be the smallest tumor size detectable by present diagnostic modalities., Methods: Clinicopathologic studies were performed in 57 patients with peripheral lung adenocarcinomas of 10 mm or less in diameter. Outcomes were compared with two other groups that consisted of 32 patients with adenocarcinomas between 11 and 15 mm in diameter and 35 patients with adenocarcinomas between 16 and 20 mm in diameter. Tumors were curatively resected between 1992 and 2002., Results: The mean age was 61.7 years. The following three features were more frequent: female sex (78.9%), nonsmokers (77.2%), and cases with carcinoma detected by computed tomography despite negative chest radiography (96.5%). Negative lymphatic invasion (94.7%) was significantly higher. Three cases showed lymphatic invasion that was classified as types E or F, according to Noguchi's classification. There were no cases of lymph node metastasis, pleural involvement, or intrapulmonary metastasis. Well-differentiated type was in 93.0%. Types A and B, which are noninvasive alveolar replacement-type adenocarcinomas, were significantly dominant (86.0%). The 5-year postoperative survival rate was 97.3%, which was significantly better than in the other two groups (75.5%, 78.1%)., Conclusions: Histopathologic features of most peripheral lung adenocarcinomas of 10 mm or less in diameter were types A and B. Types A and B were considered fundamentally indicated for thoracoscopic wedge resections. However, the other types required the standard operation.

Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN.

A case of a patient with a intrathoracic chronic expanding hematoma presenting as a neoplasm is reported. A chronic encapsulated intrathoracic hematoma is rare condition and is clinically included in a category of chronic hemorrhagic empyemas as a type of chronic empyemas in Japan. The clinical picture of our case suggested a slowly growing tumor. Though needle biopsy was performed, only blood was aspirated. Intraoperative findings revealed a intrathoracic hematoma with a tough capsule. It adhered to the chest wall hardly. Histopathological investigations revealed that the capsule consisted of a collagenous outer layer and a newly vascularized inner layer with fibrosis. Hemosiderin deposits suggested recurrent bleeding from fragile vessels. The mechanisms of hematoma formation and its expanding nature are discussed. The hematoma appeared to have been enlarged by repeated exudation or bleeding from capillaries inside the capsule.

Objective: In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of pIgR in the patients with and without IgAN., Subjects and Methods: Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as A1 and A2 with and without Pvu II site, respectively., Results: The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was higher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, chi2 = 9.84, P = 0.0017, Odds ratio = 1.71). Moreover, the subjects with A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other renal diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (A1 and A2; 0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, chi2 = 12.44, P = 0.0004, Odds ratio = 3.01)., Conclusion: This is the first demonstration of the pIgR gene polymorphisms in IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN.

Background: Hyperlipoproteinemia is occasionally associated with severe glomerular injury caused by abnormal accumulation of lipid in glomeruli, which occurs in conditions such as lipoprotein glomerulopathy (LPG). This study investigates the cases of two siblings with homozygous apolipoprotein (apo) E2 who show unique histologic features, massive proteinuria, and dysbetalipoproteinemia., Methods: Histologic studies were performed using renal biopsy specimens. Plasma lipoproteins were extensively characterized. The exons of the apo E genes were sequenced to avoid missing any mutations., Results: Histologically, the siblings' condition resembled LPG by light microscopy studies. Electron microscopy studies revealed large lipoid deposits in the paramesangium, subendothelium, and subepithelium of the glomeruli, which were different from LPG in terms of not forming the layered structure resembling a fingerprint even in large lipoprotein thrombi, and mesangial foam cells. Immunohistochemically, the lipoid deposits contained apo E and apo B. These patients did not have either diabetic nephropathy or other known forms of glomerulonephritis. The sequence of exons of the apo E genes revealed homozygosity for apo E2 in both cases., Conclusion: The extensive lipoprotein deposition in glomeruli, which resembles LPG, can also occur in apo E2 homozygous individuals, but in a distinct fashion. Because the two cases were siblings, they may have other shared alleles, in addition to the apo E2 allele, that negatively affect processing of lipoproteins and lead to abnormal accumulation of lipoprotein deposits in glomeruli.

This study investigates the circadian blood pressure variation of non-diabetic chronic hemodialysis (HD) patients on both HD and non-HD days as well as the factors affecting diurnal BP variation. Forty-nine HD patients aged 61.8 +/- 12.9 years who were on daytime HD for 97 +/- 68 months were studied. No significant difference was found in every daytime and nighttime BP between the first (HD) and the second (non-HD) day. However, the ratio nighttime/daytime BP was significantly higher on the second day. Each BP diurnal variability pattern was classified as either Dipper (D: the ratio nighttime/daytime mean BP 0.8-0.9), non-dipper (0.9 < ND < 1.0), or inverted dipper (ID > 1.0). More than 75% of the cases were classified as ND (26 cases) or ID (11 cases). The ultrafiltration rate in D was significantly less than that in ND and ID. The difference of plasma renin activity between pre- and post-HD (dRen) was significantly higher in ID than in D and ND. The amount of dialysis (Kt/V) was found to be significantly correlated with nighttime BP fall. Ultrafiltration, dRen and Kt/V were independent factors for the abnormal BP diurnal variability. In conclusion, the decreased nocturnal BP fall seen in non-diabetic HD patients is associated with increased extracellular fluid even in the patients without overt overhydration, whereas relatively insufficient amount of dialysis (low Kt/V) may be another possible cause. The increased dRen observed only in ID patients may reflect occult cardiovascular damage or functional disturbances in aortic and carotid baroreflexes caused by arterial structural changes.

We report here the temperature-dependent unoccupied molecular orbitals (MO's) of C60 molecules adsorbed on a Si(001)-(2 x 1) surface measured using near edge x-ray absorption fine structure (NEXAFS). At 300 K, the NEXAFS spectrum reveals that the interaction between a 1.0 monolayer (ML) C60 film and a Si(001) surface is mainly the van der Waals force. After annealing the samples at 500 K, we observe an increment in the full-width at half-maximum of unoccupied MO's, which indicates the change of the interaction. Moreover, the lowest unoccupied molecular orbital (LUMO) shifts to the higher photon energy side and the intensity of the LUMO+1 relative to that of the LUMO+3 decreases in the NEXAFS spectrum. These results suggest that the strong interaction induced at 500 K has a covalent character, to which the LUMO+1 contributes.

Pulmonary aspergillosis and lung cancer rarely occur simultaneously. We report a 66-year-old man with a round shadow in the thin-wall cavity of the right upper lobe. Radiological findings and transbronchial biopsy revealed squamous cell carcinoma complicated by aspergilloma at the site. Right upper lobectomy suggested that early lung cancer arose from preexisting lung scars containing an aspergilloma.

Agene encoding olfactomedin-related glycoprotein was isolated from rat glomerulus despite its prior identification as a neuron-specific gene. The mRNA expression was remarkably intense in renal glomerulus and brain and faint in the lung and eye among rat systemic organs. Although the brain contained four mRNA variants (AMY, AMZ, BMY, and BMZ) transcribed from a single gene, the glomerulus, lung, and eye expressed only two variants (BMZ and BMY). The glycoprotein was intensely immunolocalized in glomerular podocytes and neurons by using an antibody against synthetic peptide of the M region, but weak in endothelial cells of the kidney and lung. Bronchiolar epithelial cells in the lung, and ciliary, corneal, and iris epithelial cells in the eye were also stained. Immunogold electron microscopy revealed selective localization of olfactomedin-related glycoprotein at the Golgi apparatus in podocytes. In glomerular culture, the staining was also intense at a juxtanuclear region in synaptopodin-positive epithelial cells of irregular shape (phenotypic feature of podocytes), whereas it was weak in synaptopodin-negative ones of cobblestone-like appearance (phenotypic feature of parietal epithelial cells of Bowman's capsule). Interestingly, Western blot analysis identified an intense band corresponding to BMZ isoform and another faint band corresponding to BMY isoform in the glomerulus, whereas the intensity of these two bands were nearly equal in the lung and eye. In the brain, four bands corresponding to four isoforms were observed apparently. Computer sequence analysis predicted coiled-coil structures in the secondary structure of the glycoprotein similar to those in Golgi autoantigens, suggesting significant roles in the unique functions of the Golgi apparatus in rat podocytes and neurons.

The many interactions of tRNA with the ribosome are fundamental to protein synthesis. During the peptidyl transferase reaction, the acceptor ends of the aminoacyl and peptidyl tRNAs must be in close proximity to allow peptide bond formation, and their respective anticodons must base pair simultaneously with adjacent trinucleotide codons on the mRNA. The two tRNAs in this state can be arranged in two nonequivalent general configurations called the R and S orientations, many versions of which have been proposed for the geometry of tRNAs in the ribosome. Here, we report the combined use of computational analysis and tethered hydroxyl-radical probing to constrain their arrangement. We used Fe(II) tethered to the 5' end of anticodon stem-loop analogs (ASLs) of tRNA and to the 5' end of deacylated tRNA(Phe) to generate hydroxyl radicals that probe proximal positions in the backbone of adjacent tRNAs in the 70S ribosome. We inferred probe-target distances from the resulting RNA strand cleavage intensities and used these to calculate the mutual arrangement of A-site and P-site tRNAs in the ribosome, using three different structure estimation algorithms. The two tRNAs are constrained to the S configuration with an angle of about 45 degrees between the respective planes of the molecules. The terminal phosphates of 3'CCA are separated by 23 A when using the tRNA crystal conformations, and the anticodon arms of the two tRNAs are sufficiently close to interact with adjacent codons in mRNA.

A family of water-selective channels, aquaporins (AQP), has been demonstrated in various organs and tissues. However, the localization and expression of the AQP family members in the gastrointestinal tract have not been entirely elucidated. This study aimed to demonstrate the expression and distribution of several types of the AQP family and to speculate on their role in water transport in the rat gastrointestinal tract. By RNase protection assay, expression of AQP1-5 and AQP8 was examined in various portions through the gastrointestinal tract. AQP1 and AQP3 mRNAs were diffusely expressed from esophagus to colon, and their expression was relatively intense in the small intestine and colon. In contrast, AQP4 mRNA was selectively expressed in the stomach and small intestine and AQP8 mRNA in the jejunum and colon. Immunohistochemistry and in situ hybridization demonstrated cellular localization of these AQP in these portions. AQP1 was localized on endothelial cells of lymphatic vessels in the submucosa and lamina propria throughout the gastrointestinal tract. AQP3 was detected on the circumferential plasma membranes of stratified squamous epithelial cells in the esophagus and basolateral membranes of cardiac gland epithelia in the lower stomach and of surface columnar epithelia in the colon. However, AQP3 was not apparently detected in the small intestine. AQP4 was present on the basolateral membrane of the parietal cells in the lower stomach and selectively in the basolateral membranes of deep intestinal gland cells in the small intestine. AQP8 mRNA expression was demonstrated in the absorptive columnar epithelial cells of the jejunum and colon by in situ hybridization. These findings may indicate that water crosses the epithelial layer through these water channels, suggesting a possible role of the transcellular route for water intake or outlet in the gastrointestinal tract.

Aquaporin (AQP) 5 gene was recently isolated from salivary gland and identified as a member of the AQP family. The mRNA expression and localization have been examined in several organs. The present study was focused on elucidation of AQP5 expression and localization in the eye, salivary gland, and lung in rat. RNase protection assay confirmed intense expression of AQP5 mRNA in these organs but negligible expression in other organs. To examine the mRNA expression sites in the eye, several portions were microdissected for total RNA isolation. AQP5 mRNA was enriched in cornea but not in other portions (retina, lens, iris/ciliary body, conjunctiva, or sclera). AQP5 was selectively localized on the surface of corneal epithelium in the eye by immunohistochemistry and immunoelectron microscopy using an affinity-purified anti-AQP5 antibody. AQP5 was also localized on apical membranes of acinar cells in the lacrimal gland and on the microvilli protruding into intracellular secretory canaliculi of the serous salivary gland. In the lung, apical membranes of type I pulmonary epithelial cells were also immunostained with the antibody. These findings suggest a role of AQP5 in water transport to prevent dehydration or to secrete watery products in these tissues.

We have successfully treated MRSA empyema after right pneumonectomy by the closed drainage and irrigation alone. The patient was a 70-year-old male who had received right pneumonectomy for p-III a squamous cell carcinoma originating in the right upper lobe bronchus. The operation wound was infected on the 6th postoperative day and became pleural fistula and finally MRSA empyema was developed on the 10th postoperative day. The chest drainage and irrigation of the infected pneumonectomy space with physiological saline containing antiseptic povidone iodine (Isodine) were performed 3 times a day for 14 days, however, the empyema was not cured completely. In addition, nausea and vomiting considered as the side effect of Isodine severely appeared. Therefore the antiseptic agent was exchanged to vancomycin hydrochloride from povidone iodine. Empyema space became sterile 4 days after the exchange and the drainage tube was removed 7 days after sterilization. Further empyema has not been developed for 8 months. We discussed the method and antiseptic agents in irrigation of empyema space.

We studied respiratory functions, extravascular lung water (EVLW) as measured by a thermodilution method using double Na indicators, and variations in polymorphonuclear leukocyte elastase (PMNE) during the acute phase following radical treatment of lung cancer, as well as to investigate clinical effect of ulinastatin. Using 16 patients with lung cancer who had undergone surgery of R 2 a or more, 10 patients without ulinastatin therapy were compared with six patients given 300,000 U/day of this drug by drip infusion from Day 0 and 4 of disease. It was found that EVLW value decreased most on Day 1, and gradually increased thereafter but did not return to the preoperative level. PMNE value increased from immediately after surgery and peaked on Day 3, but returned nearly to the preoperative level by Day 5. Although this was different from the variations in EVLW value, there was a correlation between these two parameters on Day 3 when PMNE peaked. Further, ulinastatin tended to inhibit PMNE and improve oxygenation index. Respiratory and circulatory parameters vary in complex manners during the acute phase following radical treatment of lung cancer, and could not be accurately evaluated by means of thermodilution using Na. PMNE is considered a contributing factor to pulmonary tissue disorders following radical treatment of lung cancer, and ulinastatin appeared to be effective in the postoperative management of patients undergoing radical treatment of lung cancer.

Intraoperative transfer of eight beta-lactam preparations to lung tissues was investigated by one-gram one-hour intravenous drip infusion immediately prior to operation. The Japanese drugs used were piperacillin, cefotiam, ceftizoxime, cefuzonam, latamoxef, flomoxef, cefotetan and cefbuperazone. The serum peak level was highest with cefotetan, 104.1 micrograms/ml, followed by cefbuperazone, latamoxef, ceftizoxime, cefotiam, piperacillin, flomoxef and cefuzonam, in decreasing order. Except for cefuzonam, there was a correlation between the serum peak level and the human serum protein binding rate (r = 0.89). There was a correlation (r = 0.98) between the Cmax of normal lung tissue (alveoli) level and the serum peak level (Cmax), but no correlation between the former and the human serum protein binding rate. The tumour level was lower than that in normal lung tissue (alveoli), but the tissue level at the obstructive pneumonia area was higher. The Cmax of bronchiolar tissue level was highest with cefuzonam, followed by latamoxef. There was no correlation between the Cmax of bronchiolar tissue level and the serum peak level, human serum protein binding rate or the Cmax of lung tissue (alveoli) level. It is therefore presumed that the drug level in tissue of the acute pneumonia area can be determined from the serum peak level of the respective drug. An appropriate drug for chemotherapy may be selected from beta-lactam preparations which are effective against main causative organisms in acute respiratory tract infections. Cefuzonam and latamoxef are especially useful for chemotherapy in patients with acute bronchiolitis.

Paraganglioma is a tumor arising from the extra-adrenal paraganglion system and is rarely observed in the mediastinum. The authors experienced a case of nonfunctioning paraganglioma of the upper posterior mediastinum. The patient was a 40-year-old female in whom abnormal shadows were noted in chest X-ray films taken in March, 1989. She was examined at our hospital with a diagnosis of mediastinal tumor in June of the same year. CT of the chest revealed a tumor in the upper posterior mediastinum and it was shown to be hypervascular by a DSA study. Urinary hormone levels were normal. The tumor was resected in May, 1990. The tumor, measuring 6.8 X 4.0 X 3.5 cm, was encapsulated, appeared dark red and had relatively clear borders. A histopathologic diagnosis of paraganglioma was made. The patient remains disease-free at present, 6 months after operation. Problems concerning diagnosis and treatment of mediastinal paraganglioma were evaluated with a review of cases reported in Japan.

Based on the results of a study on pulmonary tissue uptake of flomoxef (FMOX), a new antibiotic agent, in 45 patients undergoing thoracotomy, the following conclusions were drawn: 1. Immediately preoperative 1 hour-drug infusion of 1 g FMOX led to maximum serum concentration (averaging 42.4 micrograms/ml) 1 hour later, with a half-life of its beta phase of 1.26 hours. 2. Normal lung (alveolar) tissue concentration was Cmax 17.98 micrograms/g with its ratios to serum peak value being 31.8, 27.1, 22.2, 9.4, 5.9 and 5.0% at 1, 2, 3, 4, 5 and 6 hours later, respectively. 3. Bronchiolar tissue concentration was Cmax 31.91 micrograms/g, with its ratios to serum peak value being 27.8, 19.3 and 10.1% at 2, 3 and 4 hours later, respectively, indicating its good bronchiolar intra-tissue transition. The above results suggested the usefulness of FMOX for both the treatment of respiratory infections and the prevention of postoperative infections.

Bronchopleural fistula developing empyema after pulmonary resection is a fatal complication. But we have successfully treated this complication after right sleeve upper lobectomy. The patient was a 61-year-old male, who has a squamous cell carcinoma originating in the right upper lobe of the lung in the clinical stage of IIIa. Right sleeve upper lobectomy with pericardiotomy to reduce the tension of bronchial anastomosis and R2a lymph node dissection. The leakage of bronchial anastomosis was complicated on 5th postoperative day and developed aspiration pneumonia of right middle and lower lobe and empyema. Reoperation was done on 7POD and completion pneumonectomy, omentopexy and open window thoracotomy were performed. Then endotracheal tube had been inserted into the left main bronchus and he controlled under respirator. Six weeks after that fistula was cured. Empyema, which caused by methicillin resistant staphylococcus aureus, was cured by open drainage for 2 weeks and closed drainage and irrigation for 14 weeks. He discharged 16 weeks after reoperation.

Among patients with primary lung cancer who were admitted to the National Cancer Center Hospital from July 1987 to April 1988 for surgical treatments, 132 underwent preoperative transesophageal endoscopic ultrasound examination (EUS) on mediastinal lymph nodes. Of the 132 patients, 101 were pathologically evaluated and studied in this article. A GF-UM2 radial scanner with 7.5-MHz (Olympus Co Ltd) was used for image examination. The lymph nodes were diagnosed as positive for metastasis when they had thickened images, clear contours, and low echoing images of fusion or lobulation. The results obtained from 509 sites were as follows: sensitivity, 53.6 percent; specificity, 97.5 percent; positive predictive accuracy, 77.1 percent; negative predictive accuracy, 93.1 percent; and overall accuracy, 91.6 percent. The sensitivity rate was 80.6 percent excluding the result of the right superior mediastinal lymph nodes that were difficult to examine for anatomic reasons. Although EUS was considered to be an excellent method in diagnosing lymph node metastases, it had a blind angle in the field. More accurate diagnoses of mediastinal lymph node metastases could be achieved by using EUS and computed tomography (CT) together.

Remission rate of leukemia has been improved by development of recent antileukemic chemotherapy. But opportunistic infection in secondary immunodeficiency has increased. Especially pulmonary mycoses often occurs and its prognosis is poor. But if patient with leukemia complicates pulmonary mycoses, it should be cured as soon as possible and antileukemic chemotherapy should be continued. We successfully performed surgical treatment for 2 pulmonary aspergillosis, which were complicated in stage of remission induction of acute leukemia.

A 59-old woman visited to our hospital with complaint of uttering stenotic sound at expiratory stage. Her chest X-ray film showed a suspicious intratracheal tumor, which was arising from the left side of the tracheal wall and confirmed 4 cm from the vocal cord by bronchofiber scope. The biopsy specimens showed well differentiated papillary adenocarcinoma. The lesion was judged to be a intrathoracic thyroid carcinoma and to infiltrate the trachea. Her air way failed to be ensured with YAG-LASER. Therefore, a subemergency operation was done. The intrathoracic lesion had no sequence of the thyroid gland. Two occult thyroid carcinomas were intraoperatively discovered. She underwent total thyroidectomy and sleeve trachectomy whose anastomosis was wrapped up in an omental flap. The intraluminal part of the tumor histologically showed poorly differentiated carcinoma, in contrast to the extratracheal part of the tumor showing well differentiated carcinoma. She was treated with radioactive iodine due to her positive 131I scintigraphy. Nine months later, a very similar lesion newly developed at the left side of trachea and made same symptoms.

A 67-year-old woman who was diagnosed as a relative early primary tracheal adenoid cystic carcinoma by preoperative examination underwent surgical resection. The histopathological extension of this carcinoma into the tracheal wall was much greater than was suggested before operation and 6 tracheal rings was curatively resected circumferentially. Median sternotomy and transection of the left brachiocephalic vein facilitated access to the trachea. To resect the extensive segment of the trachea, the right pulmonary ligament and hilum were mobilized. Additionally Dedo's laryngeal release was performed to lessen the tension at the anastomosis. Then the flap of the pleura and adipose tissue with the right internal mammary artery and vein was wrapped around the anastomosis for revascularization and protection of brachiocephalic artery. The postoperative course was not eventful. The postoperative dysphagia by Dedo's laryngeal release was mild and resolved within 7 days after operation. And the postoperative mammary arteriography showed the vessels around the anastomosis. This wrapping procedure is easy and does not need a laparotomy. So we think it is beneficial for prevention against postoperative complications of tracheoplasty.

From our study on cefuzonam (CZON), a new antibiotic agent, with regard to pulmonary tissue uptake and use in prophylaxis of postoperative infections in 20 patients undergoing thoracotomy, we were able to reach the following conclusions: 1. Following intravenous infusion over 1 hour of 1 g of CZON immediate preoperatively, the mean serum concentration at 1 hour after commencement of the infusion reached at 41.5 micrograms/ml (serum peak value), then gradually decreased with a half-life in the beta-phase of 1.20 hours. 2. The mean CZON concentration in normal pulmonary tissue at 1 hour after commencement of the infusion was 12.7 micrograms/g with a half-life in the beta-phase of 1.28 hours. Although the number of cases examined was small at only 4, the mean pulmonary tissue level in obstructive pneumonitic lesions was 13.7 micrograms/g, and an average half-life in the beta-phase was 1.65 hours. 3. Mean bronchiolar CZON concentrations at 2, 4, and 6 hours after commencement of the infusion were 14.5, 3.1, and 2.8 micrograms/g, respectively, with a half-life in the beta-phase of 3.53 hours. 4. Among the patients undergone thoracotomy with use of CZON, no postoperative infections occurred nor severe adverse reaction was observed. CZON attained good transfer in the pulmonary tissues, particularly in the bronchiolar tissue, hence it appears useful as a prophylactic against postoperative infections in respiratory disease.

The pedicled omentum finds use in chest surgery for management of complicated problems and prevention of serious complications. Nine patients have been treated with the pedicled omentum. In four patients the goal was preventive, to avoid anastomotic leakage or infection, or to provide a source of neovascularity. In five patients the pedicled omentum was used to obtain healing in the presence of infection. Bronchial fistula, esophageal fistula with pyothorax or mediastinal infections treated successfully. This series demonstrates the efficacy of the pedicled omentum in management of chest problems.

From 1962 to 1987, 72 patients with primary colorectal cancer underwent surgical treatment for pulmonary metastases. The overall cumulative 5 year survival rate was 41.3%. But the cumulative 1 year survival rate of patients with incomplete resection was 20.0%. Reduction surgery should not be employed. Twenty-nine of 66 patients with complete resection have recurred. The most of first manifested recurrences were in the lung and within 18 months after thoracotomy. This tendency was remarkable in patients with multiple pulmonary metastases and all recurrences of them were within 18 months and 80% were multiple in bilateral lung. Almost all multiple pulmonary metastases seemed to be only one manifestation of generalized metastatic disease. So indication of surgical treatment for them should be cautious. Type of pulmonary resection had no influence on post-thoracotomy survival rate. But in patients with partial resection, 7 recurrences at surgical margin and one recurrence on regional lymph nodes were doubted. Four metastatic lesions less than 3cm in maximum diameter had metastases to the regional lymph nodes. To resect more curatively, lobectomy and systemic lymphadenectomy should be recommended as the standard operation for pulmonary metastases of colorectal cancer.