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Biomedical subjects

N Yamanaka

Publications and source records attributed to N Yamanaka.

At least 19 recordsLinked to original sources

Polychlorinated dibenzo-p-dioxins, -dibenzofurans, and biphenyls in domestic animal food stuff and their fat.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzo-p-dioxins (PCDFs) and dioxin-like coplanar PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) were measured in domestic animal related samples such as feed ingredient, mixed feed and animal fat from Japan. The mean concentration of total PCDDs, PCDFs and coplanar PCBs in fish oil was 17000pg g-1 lipid wt, which 9- to 30-fold greater than that from other animal originated ingredients. Mixed feed for chicken and chicken fat contained greater total PCDDs, PCDFs, coplanar PCBs concentrations (190 and 2100pg g-1 lipid wt) compared to those for pig (120 and 320pg g-1 lipid wt). WHO-TEQs were ranged 0.39-13, 0.15-0.22 and 0.73-2.8pg g-1 lipid wt for ingredients, mixed feeds and animal fats, respectively. Greater biomagnification factor was noticed for congeners 1,2,3,7,8-PeCDD, 1,2,3,6,7,8-HxCDD, 2,3,7,8-TCDF and 1,2,3,4,7,8-HxCDF in chicken and pig fat. Biomagnification factors for both mono- and non-ortho coplanar PCBs were greater in chicken fat compared to those in pig fat.

Adipose Tissue↗

A new computer-assisted method for measuring the tibio-femoral angle in patients with osteoarthritis of the knee.

OBJECTIVE: The purpose of this study was to evaluate the inter- and intraobserver variability in measuring the tibio-femoral angle using our new computer-assisted method, and to compare it with a conventional manual method. METHODS: Radiography of all patients of osteoarthritis of the knee in outpatient were performed with standing on both legs, and with conventional antero-posterior weight bearing view of the knee fully extended. Three examiners measured the tibio-femoral angle with the computerized method in 52 subjects with osteoarthritis (73 knees). The tibio-femoral angle was measured using a computer-assisted method in which the observer must visually determine and select eight points on the margins of the femur and tibia on a radiographic image displayed on a computer monitor. The inter- and intraobserver Intra-class correlation (ICC) was analyzed. RESULTS: The interobserver mean correlation of computer-assisted method was 0.970 with a mean difference of 0.38 degrees (S.D. 1.125 degrees). The intraobserver mean ICC of computer-assisted method was 0.973, with a mean difference of 0.16 degrees (S.D. 1.12 degrees). An analysis of the difference between conventional methods and our new system showed a mean ICC of 0.922, with an intersystem mean difference of 0.295 degrees (S.D. 1.82 degrees). CONCLUSION: Our computer-assisted method of measuring the tibio-femoral angle was simple, easy, and quick, and should be considered as an alternate method for measurement.

Adult↗

Detection of Cry1Ab protein in gastrointestinal contents but not visceral organs of genetically modified Bt11-fed calves.

The fate of insecticidal Cry1Ab protein was examined in the gastrointestinal (GI) contents and visceral organs of calves fed insect-resistant genetically modified maize Bt11. Twelve cross-breed (Japanese black x Holstein) calves were fed either Bt11 or non-genetically modified isoline maize for 90 d. Peripheral blood, rumen juice and feces were collected fortnightly, and GI contents and visceral organs were collected at slaughter at the end of the experiment. Samples were checked for Cry1Ab protein by immunological methods, and visceral organs were examined pathologically. Trace amounts of Cry1Ab protein were detected in the GI contents but not in the liver, spleen, kidney, muscle or mesenteric lymph nodes. No lesions were observed pathologically. Cry1Ab protein in the feces was degraded quickly at atmospheric temperature. These results suggested that only a trace amount of Cry1Ab protein survived passage through the GI tract but was not transferred to liver, spleen, kidney, lymph nodes or muscles.

Animals↗

HIV mucosal vaccine: nasal immunization with rBCG-V3J1 induces a long term V3J1 peptide-specific neutralizing immunity in Th1- and Th2-deficient conditions.

In the vaccine strategy against HIV, bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is considered to be one of potential vectors for mucosal delivery of vaccine Ag. We analyzed the induction of the Ag-specific Ab response by nasal immunization with recombinant BCG vector-based vaccine (rBCG-V3J1) that can secrete the V3 principal neutralizing epitope of HIV. Mice were nasally immunized with rBCG-V3J1 (10 microg) three times at weekly intervals. Four weeks after the initial immunization, high titers of V3J1-specific IgG Abs were seen in serum. These high levels of HIV-specific serum IgG responses were maintained for >12 mo following nasal immunization without any booster immunization. V3J1-specific IgG-producing cells were detected in mononuclear cells isolated from spleen, nasal cavity, and salivary gland of the nasally vaccinated mice. Nasal rBCG-V3J1 also induced high levels of prolonged HIV-specific serum IgG responses in Th1 (IFN-gamma(-/-))- or Th2 (IL-4(-/-))-immunodeficient mice. Further, IgG3 was highest among V3 peptide-specific IgG subclass Ab responses in these immunodeficient mice as well as in wild-type mice. In addition, this Ag-specific serum IgG Abs induced by nasal immunization with rBCG-V3J1 possessed the ability to neutralize clinical isolate of HIV in vitro. These results suggested that the nasal rBCG-V3J1 system might be used as a therapeutic vaccine in addition to a prophylaxis vaccine for the control of AIDS.

AIDS Vaccines↗

An informative linkage map of soybean reveals QTLs for flowering time, leaflet morphology and regions of segregation distortion.

A genetic linkage map covering a large region of the genome with informative markers is essential for plant genome analysis, including identification of quantitative trait loci (QTLs), map-based cloning, and construction of a physical map. We constructed a soybean genetic linkage map using 190 F2 plants derived from a single cross between the soybean varieties Misuzudaizu and Moshidou Gong 503, based on restriction-fragment-length polymorphisms (RFLPs) and simple-sequence-repeat polymorphisms (SSRPs). This linkage map has 503 markers, including 189 RFLP markers derived from expressed sequence tag (EST) clones, and consists of 20 major linkage groups that may correspond to the 20 pairs of soybean chromosomes, covering 2908.7 cM of the soybean genome in the Kosambi function. Using this linkage map, we identified 4 QTLs--FT1, FT2, FT3, and FT4--for flowering time, the QTLs for the 5 largest principal components determining leaflet shape, 6 QTLs for single leaflet area, and 18 regions of segregation distortion. All 503 analyzed markers identified were located on the map, and almost all phenotypic variations in flowering time were explained by the detected QTLs. These results indicate that this map covers a large region of the soybean genome.

Chromosome Mapping↗

Left hemihepatectomy with microsurgical reconstruction of the right-sided hepatic vasculature. A strategy for preserving hepatic function in patients with proximal bile duct cancer.

BACKGROUND: Right hemihepatectomy (RH) for proximal bile duct cancer occasionally results in liver failure. We report the feasibility of left hemihepatectomy (LH) with vascular reconstruction (VR) of the right-sided hilar vessels to preserve hepatic reserve. METHODS: Among 110 patients with proximal bile duct cancer (PBC) treated between January 1980 and December 1998, 11 patients underwent LH with VR of eight portal veins and nine hepatic arteries, and 14 underwent RH with VR of four portal veins and one hepatic artery. Microsurgical techniques were used in 80% (8/10) of the hepatic arterial reconstructions. RESULTS: Although operation time was significantly longer in the LH group, hospital mortality, blood loss and incidence of histologically cancer positive margin at the bilioenteric anastomotic site were similar in the two groups. Peak serum liver enzyme concentration was significantly higher in the LH group with longer inflow occlusion time, whereas peak serum total bilirubin concentration was significantly higher in the RH group, which had smaller liver remnant. No liver abscess occurred in any patients who underwent microvascular reconstructions. The cumulative survival of the LH group was worse than that of the RH group, in which the proportion of vascular invasion was lower, but not significantly. CONCLUSION: LH with right-sided microvascular reconstruction is technically possible and a feasible option when RH is likely to result in postoperative liver failure.

Bile Duct Neoplasms↗

The protective effect of hepatocyte growth-promoting factor (pHGF) against hydrogen peroxide-induced acute lung injury in rats.

To examine the protective effect of hepatocyte growth-promoting factor (pHGF) in hydrogen peroxide (H(2)O(2))-induced acute lung injury in rats, we observed the pathological changes in lung tissue by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and by light and electron microscopy. We also measured the serum levels of lipid peroxide (LPO). At 6 to 24 h after H(2)O(2) injection, the level of LPO was significantly higher in the H(2)O(2) group than in the H(2)O(2) + pHGF-treated group. This finding indicated that pHGF protected against cell membrane damage in H2O2-induced acute lung injury. Positive TUNEL signals were found in capillary endothelial cells, alveolar epithelial cells, and inflammatory cells. In the H(2)O(2) + pHGF-treated group, TUNEL-positive signals were reduced compared with those in the H(2)O(2) group. This finding indicated that pHGF acts to suppress apoptosis. In the H(2)O(2) group, severe pulmonary edema was seen 3 h after H(2)O(2) injection, and at 24 h, severe atelectasis was seen. In the H(2)O(2) + pHGF-treated group, pulmonary edema was scarcely seen and severe atelectasis was not found. This finding indicated that pHGF acts to suppress both severe pulmonary edema and atelectasis. In the H(2)O(2) group, the formation of subendothelial blebs and disruption of endothelial cells was observed. Edema and disruption were seen in type I epithelial cells. In type II lung epithelial cells, mitochondria were swollen and microvilli had disappeared. In the H(2)O(2) + pHGF-treated group, the formation of subendothelial blebs was seen, but no severe subendothelial blebs were observed. Disruption of capillary endothelial cells and type I epithelial cells was not evident, nor was there damage to type II lung epithelial cells. These findings indicated that pHGF protects the progression of H(2)O(2)-induced acute lung injury, and showed that pHGF acts to stabilize the cell membrane in capillary endothelial cells and lung epithelial cells.

Animals↗

Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats.

The development of nephrocalcinosis in rats fed a high phosphorus diet, and the effectiveness of the Chinese traditional medicine, Wulingsan, and its components (Poria, Alismatis Rhizoma, Atractylodis Rhizoma, Cinnamomi Ramus, Polyporus) in suppressing the development of calcinosis were studied. The rats were fed a high phosphorus diet (1.5% P) supplemented with Wulingsan or its individual components (0.5 g/kg body weight) as separate experimental groups for a 2-week period. Upon histological observation by light microscopy and electron microscopy, signs of nephrocalcinosis were observed in almost all areas of the kidney. Calculi, consisting mainly of needle-shaped crystals of hydroxyapatite, were observed in the proximal tubules, in the collecting ductal lumina, and in the mitochondria of the proximal tubular cells and the interstitial cells. X-ray microanalysis revealed that the calculi were composed of hydroxyapatite (Ca and P). In the group fed the diet supplemented with Wulingsan, the severity of calcinosis in the corticomedullary junction was only slight. In all groups fed individual components of Wulingsan, the severity of calcinosis was almost the same as that in the group fed the high phosphorus diet (1.5% P). Wulingsan suppressed the development of calcinosis in rats fed the high phosphorus diet supplemented with this Chinese medicine, whereas its individual components alone had no effect. The process of calcinosis and the mechanism responsible for the activity of this Chinese medicine in the suppression of calcinosis are discussed.

Animals↗

Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis.

Vascular endothelial growth factor (VEGF) regulates angiogenesis through endothelial cell proliferation and plays an important role in capillary repair in damaged glomeruli. We tested the hypothesis that VEGF might be beneficial in rats with severe glomerular injury in glomerulonephritis (GN) based on its angiogenic and vascular remodeling properties. Acute GN with severe glomerular destruction was induced in rats by injection of anti-Thy-1.1 antibody (day 0) and Habu-snake venom (day 1). Rats were intraperitoneally injected with recombinant human VEGF(165) (10 microg/100 g body wt/day) or vehicle from day 2 to day 9, and monitored changes in glomerular capillaries, development of glomerular inflammation, and progression to glomerular sclerosis after acute glomerular destruction in both groups. Rats that received anti-Thy-1.1 antibody and Habu-snake venom showed severe mesangiolysis and marked destruction of capillary network on day 2. VEGF was expressed on glomerular epithelial cells, proliferating mesangial cells, and some infiltrating leukocytes, and VEGF(165) protein levels increased in damaged glomeruli during day 5 to day 7. Normal, damaged, and regenerating glomerular endothelial cells expressed VEGF receptor flk-1. However, endothelial cell proliferation and capillary repair was rare in vehicle-treated rats with severe glomerular damage, which progressed to global sclerosis and chronic renal failure by week 8. In contrast, in the VEGF-treated group, VEGF(165) significantly enhanced endothelial cell proliferation and capillary repair in glomeruli by day 9 (proliferating endothelial cells: VEGF(165), 4.3 +/- 1.1; control, 2.2 +/- 0.9 cells on day 7, P < 0.001; and glomerular capillaries: VEGF(165), 24.6 +/- 4.8; control, 16.9 +/- 3.4 capillaries on day 7, P < 0.01). Thereafter, damaged glomeruli gradually recovered after development of capillary network by week 8, and significant improvement of renal function was evident in the VEGF-treated group during week 8 (creatinine: VEGF(165), 0.3 +/- 0.1; control, 2.6 +/- 0.9 mg/dl, P < 0.001; proteinuria: VEGF(165), 54 +/- 15; control, 318 +/- 60 mg/day, P < 0.001). We conclude that the beneficial effect of VEGF(165) in severe glomerular injury in GN emphasizes the importance of capillary repair in the resolution of GN, and may allow the design of new therapeutic strategies against severe GN.

Animals↗

Role of MMP-2 in alveolar epithelial cell repair after bleomycin administration in rabbits.

Matrix metalloproteinases (MMPs) have been implicated in the pathological processes of interstitial lung diseases. However, underlying mechanisms, particularly for activity levels and distribution of activated MMP-2 in the disease process, are yet to be elucidated. The present study investigated the immunolocalization of MMP-2, membrane type 1-matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase (TIMP)-2, p53, and Ki-67 in a rabbit model of bleomycin-induced pulmonary fibrosis. Gelatin zymography and in situ zymography were used to examine the activity and the localization of MMP-2. Furthermore, we performed Western blot and in situ hybridization for MT1-MMP, an activator for MMP-2. The total MMP-2 level estimated by gelatin zymography increased significantly at 3, 7, and 14 days after bleomycin administration, compared with controls. In the immunohistochemical study, immunoreaction for MMP-2 was strongest in alveolar epithelial cells among the cell populations. Swollen and/or elongated type II alveolar epithelial cells showed strong immunoreactions for MMP-2, MT1-MMP, and TIMP-2. After bleomycin administration, immunoreaction for p53 was observed in bronchiolar and alveolar epithelial cells. The proportion of p53-positive cells was high in epithelial cells from 1 to 14 days as MMP-2 levels were increased, suggesting that p53 may be responsible, at least in part, for the increase of MMP-2. The ratio of activated MMP-2 to total MMP-2 estimated by gelatin zymography increased significantly at 3, 7, 14, and 28 days after bleomycin treatment. In situ zymography revealed that type II alveolar epithelial cells degraded gelatin. An increased expression of MT1-MMP protein was observed by Western blot following administration of bleomycin. In situ hybridization demonstrated that type II alveolar epithelial cells gave intense signal for MT1-MMP mRNA. These results suggest that type II alveolar epithelial cells express MT1-MMP and activate MMP-2 on their cell surfaces, which may lead to the elongation and migration of alveolar epithelial cells in the repair process of bleomycin-induced pulmonary fibrosis.

Animals↗

Lower abdominal phlegmon due to spontaneous rupture of an ileal neobladder.

A case is presented of spontaneous rupture of an ileal orthotopic neobladder due to a large residual urine volume. The present case is the 13th such case reported; however, this case is the first to show lower abdominal phlegmon and in which the perforation site was detected using computed tomography scanning. The indications for neobladder should be considered with great care. If spontaneous rupture is suspected, an early diagnosis of the perforation site and a measure of the extravasation volume using computed tomography are necessary. Appropriate treatment should include laparotomy.

Abdomen↗

Bladder reconstruction with autotransplanted ileum in the dog: better functional results than standard enterocystoplasty.

OBJECTIVE: To compare, in a dog model, the properties of a reconstructed bladder (peristalsis, histological changes and absorption) using an autotransplanted ileal segment with standard enterocystoplasty. MATERIALS AND METHODS: Female beagle dogs were divided into two groups. In group 1 (autotransplantation, six dogs), a Heineke-Mikulicz-type pouch was constructed using autotransplanted terminal ileum. The artery and vein of the terminal ileum were anastomosed to the iliac artery and vein, respectively. The pouch was anastomosed to the bladder remnant immediately above the vesical triangle. In group 2 (control, five dogs) the same type of bladder reconstruction using terminal ileum was undertaken but with no vessel anastomosis. Bladder function in these two groups was then compared for peristalsis (by monitoring intravesical pressure), histological changes (by microscopy) and glucose reabsorption (by measuring the amount of glucose remaining in the reconstructed bladder). The mean (range) follow-up was 11 (7-18) months for group 1 and 9.2 (7-12) months for group 2; the recovery time before examination was 4.6 (2-7) months for group 1 and 4.0 (2-6) months for group 2. RESULTS: In group 1, there were no major complications in five dogs after the procedure and they survived for > 7 months; the autotransplant became necrotic in one dog where the arterial diameter was < 1 mm. In the control group, all five dogs survived for > or = 7 months after surgery. Intestinal peristalsis was inhibited in group 1 but not in group 2. The bladder was oval/spherical in group 1 and elongated in group 2, with a thinner epithelium and fewer goblet cells in the latter. Glucose reabsorption was greater in group 2 than in group 1. CONCLUSION: Bladder reconstruction using autotransplanted terminal ileum in dogs is technically feasible. For bowel peristalsis and reabsorption of glucose, autotransplanted ileum may have functional advantages over a standard enterocystoplasty.

Absorption↗

Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and its density as a predictor for the extent of prostate cancer.

OBJECTIVE: To determine whether serum levels of the prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND METHODS: Serum samples were obtained from 62 patients with clinically localized prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. The relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer, the mean PSA and PSA-ACT levels were significantly lower than in those with extraprostatic disease. Furthermore, there were significantly higher mean PSAD and ACTD levels in men with extraprostatic than with organ-confined disease. There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at each pathological stage, whereas there was no significant association between these variables and the Gleason score. Receiver-operating characteristic curve analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a larger area under the curve than PSA and PSAD, respectively, but these differences were not significant. Furthermore, PSA-ACT and ACTD provided significantly better sensitivity for detecting organ-confined disease than PSA and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD.

Aged↗

Engraftment of tonsillar mononuclear cells in human skin/SCID mouse chimera--validation of a novel xenogeneic transplantation model for autoimmune diseases.

Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical tonsillar focal infections, based on the marked clinical improvement of the skin lesions after tonsillectomy. Despite the accumulation of data showing the clinical efficacy of tonsillectomy for this skin lesion, fundamental etiological and pathophysiological issues have yet to be addressed. One primary obstacle hindering investigators has been the lack of an appropriate animal model for this human skin disorder. In the early stage of PPP, it has been reported that lymphocytes, predominantly CD4+ T lymphocytes, infiltrate the palmar and plantar skins. However, the origin and mechanism of infiltration by these lymphocytes is not clear and there are very few reports on whether tonsillar mononuclear cells react directly with the skin. We have been intrigued by the ability to engraft human cells onto severe combined immunodeficiency (SCID) mice, together with the opportunity for long-term graft survival and ability to adoptively transfer various human immunocompetent cells. In this review, we addressed the existing deficiencies in our understanding of the relationship between tonsils and PPP by using emerging transplantation technology involving SCID mice.

Animals↗

Apoptosis mediates decrease in cellularity during the regression of Arthus reaction in cornea.

BACKGROUND/AIMS: The Arthus type allergic reaction is characterised by inflammatory cell infiltration and marked neovascularisation in the cornea. During the healing stages, inflammatory cells and newly formed microvessels gradually disappear. The aim was to establish whether apoptosis affected the regression of inflammatory cells and newly formed microvessels, in order to define more clearly the cellular mechanisms involved in the pathobiology of corneal diseases. METHODS: Albino male rabbits were injected subcutaneously with 5 mg/ml bovine serum albumin (BSA) incorporated in Freund's complete adjuvant twice weekly. Under the anaesthesia, 30 microl of a 0.5 mg/ml BSA solution was injected into the central corneal stroma to induce an Arthus type allergic reaction. The injured corneas were collected at various time points ranging from 3 to 20 days. Apoptotic cells were identified by both light microscopy using in situ TdT-dUTP nick end labelling (TUNEL) method and electron microscopy. RESULTS: With increasing time after induction of the Arthus reaction, marked neovascularisation and infiltrated inflammatory cells such as polymorphonuclear cells (PMNs) and plasma cells were observed in the cornea. Thereafter, the inflammatory cells and newly formed microvessels gradually disappeared. Coincidently, the numbers of microvessel endothelial cells and infiltrated inflammatory cells undergoing apoptosis were increased. Apoptotic bodies were taken up by macrophages, PMNs, as well as myofibroblasts derived presumably from transformation of migrated keratocytes. CONCLUSIONS: These data demonstrate that regression of the cellular infiltrates and microvessel endothelial cells associated with the Arthus reaction in the cornea occurs via apoptosis. This finding adds insights into the cellular mechanisms regulating the pathobiology of corneal diseases.

Animals↗

Ileal neobladder for urinary bladder replacement following total pelvic exenteration for rectal carcinoma.

OBJECTIVE: The aim of this study was to determine the feasibility of using the ileal neobladder as a substitute for the urinary bladder following total pelvic exenteration for rectal carcinoma. PATIENTS AND METHODS: Between 1992 and 1998, we performed total pelvic exenteration with ileal neobladder in 5 men with rectal carcinoma. Four patients had primary tumors, and one had recurrent disease after low anterior resection for rectal carcinoma. Histological types were adenocarcinoma in 4 and squamous cell carcinoma in 1. Invaded organs were: the urinary bladder in 1, the urinary bladder and prostate in 2, the prostate and seminal vesicle in 1, and the prostate in 1. RESULTS: There was no operative death. In 1 patient, an ileal conduit was needed because of partial necrosis of the neobladder. Minor leakage on the dorsal wall of the neobladder occurred in 2 patients, which was successfully stopped with simple closure and a gluteus maximus fasciocutaneous flap, respectively. All except one patient with the ileal conduit could void via the urethra. Complete daytime urinary continence was achieved, but nocturnal continence was maintained with voiding once or twice per night. As the urodynamic state, the mean maximum flow rate was 20.9 ml/s (range 9.0-34.1), the mean average flow rate was 7.7 ml/s (range 3.0-11.0), and the mean voided volume was 285.5 ml (range 160-432). The mean length of follow-up was 47.8 months. One patient died of local recurrence 38 months postoperatively, and 1 died of pneumonia 10 months postoperatively. Both patients could void via the urethra until death. The other three patients are currently alive without any evidence of recurrence. CONCLUSIONS: Although total pelvic exenteration is a laborious surgical procedure, an ileal neobladder could be a good alternative to the urinary bladder enabling the patients to void via the urethra with urinary continence.

Adenocarcinoma↗

Tubulointerstitial injury of Thy-1 nephritis in uninephrectomized stroke-prone spontaneously hypertensive rats.

Thy-1 nephritis was induced in stroke-prone spontaneously hypertensive rats (SHR-SP) with unilateral nephrectomy (UNX) and normotensive same genetic strain Wistar-Kyoto (WKY) rats with UNX to evaluate whether the tubulointerstitial injury in Thy-1 nephritis is accelerated by long-term systemic and intraglomerular hypertension. SHR-SP that underwent UNX at twelve weeks of age were randomly assigned to receive monoclonal anti-thy 1.1 antibody (group SP), and normal saline (group SC). Age-matched normotensive WKY rats served as controls and were given the same dose of monoclonal anti-thy 1.1 antibody after UNX (group WK). In all groups, the blood pressure and renal function were assessed, and morphologic changes of tubulointerstitium were examined by using immunohistochemistry and light microscopy twelve weeks after Thy-1 nephritis induction (in groups SP and WK) and UNX alone (in group SC). In all groups, histological findings, the degree of monocyte/macrophage infiltration, interstitial expression of alpha-smooth muscle actin (alpha-SMA), which is a marker for myofibroblasts, and the degree of tubular cell proliferation were examined. In addition, assessments of blood pressure, serum creatinine and BUN levels, and the degree of proteinuria were made. In parallel to glomerular structural damage, interstitial fibrosis with predominant monocyte/macrophage influx, increased interstitial expression of alpha-SMA and tubular cell proliferation were observed in group SP. A significant increase in serum creatinine and proteinuria were also present in this group. In contrast, the changes observed in group SC were not so evident or extensive as in group SP. The level of proteinuria was lower than that in group SP. No evident tubulointerstitial changes were found in group WK. The results showed that tubulointerstitial injury was prominently progressed in the hypertensive model with Thy-1 nephritis. This suggests that sustained systemic and glomerular hypertension is not only ultimately responsible for the progression of immunologically mediated glomerular injury, but is also responsible for subsequent tubulointerstitial changes. Migration and proliferation of myofibroblasts and intense influx of monocytes/macrophages may contribute to the development of tubulointerstitial fibrosis.

Animals↗

High survival rate of 6 cases of pulmonary large cell neuroendocrine carcinoma formerly classified as small cell carcinoma.

UNLABELLED: In the revised WHO classification of lung cancer, published in 1999, large cell neuroendocrine carcinoma (LCNEC) was employed as a new histological entity. LCNEC is generally considered a high-grade malignant lung cancer, and appropriate treatment remains to be determined. Before its new classification, LCNEC had long been classified into several entities. Advancing the review of previous cases in Nippon Medical School Hospital, we noticed that some LCNEC patients were formally diagnosed as having small cell lung cancer (SCLC), and they showed long-term survival. MATERIAL AND METHODS: All histological specimens of surgically resected SCLC in Nippon Medical School Hospital were reclassified according to the 1999 WHO classification manual. Their neuroendocrine differentiations were confirmed by the use of immunostainings with chromogranin A and synaptophysin. RESULTS: Fourteen cases satisfied the qualifications for both histological and clinical reevaluation. Among them, 6 patients were reclassified as LCNEC, and their stage distribution was as follow: IA; 1, IB; 2, IIIA; 2, and IIIB; 1. Their survival term ranged from 33.8 to 78.0 months; 5 were still alive, and 1 (IIIB) died 57.6 months after surgery. DISCUSSION: According to this study, all the LCNEC patients who were treated as SCLC patients showed more favorable prognoses than patients described in published studies, even overall lung cancer. Therefore, it is suggested that multimodality therapy for SCLC may improve the prognoses of patients with LCNEC.

Aged↗