Pentaketides relating to aspinonene and dihydroaspyrone from a marine-derived fungus, Aspergillus ostianus

Three new pentaketides, aspinotriols A ( 1) and B ( 3) and aspinonediol ( 5), were isolated together with two known compounds, aspinonene ( 7) and dihydroaspyrone ( 9), from the marine fungus Aspergillus ostianus strain 01F313, which was collected in Pohnpei and cultured with bromine-modified artificial seawater. The structures of the new compounds were determined by spectroscopic analyses including 1D and 2D NMR. Although 1 and 3 are diastereomers, they show nearly superimposable (1)H and (13)C NMR spectra. The absolute configurations of compounds 1, 3, 5, and 9 were elucidated by the modified Mosher's method.     

Case of immune complex crescentic glomerulonephritis with consistently high titers of MPO-ANCA for 6 years

A male patient, now 65 years old, experienced fever, hemoptysis, and respiratory failure about six years ago. Soon thereafter, he developed rapid progressive renal dysfunction with pulmonary hemorrhage and positive findings for MPO-ANCA. We commenced methylprednisolone pulse (MP) therapy followed by oral prednisolone (PSL) and intravenous cyclophosphamide (CY) for the treatment of ANCA-associated microscopic polyangiitis (MPA). Therapeutic efficacy was obtained comparatively rapidly. Light microscopic findings of a percutaneous renal biopsy demonstrated focal necrotizing and crescentic glomerulonephritis. Immunofluorescent microscopy indicated diffuse deposition of IgG and C3 along the periphery of the tufts and in the mesangium. On the basis of these findings, the condition was diagnosed as immune complex crescentic glomerulonephritis associated with MPO-ANCA. MPO-ANCA titers were high (714 EU) at onset and remained high (250-450 EU) over the ensuing 6 years with oral administration of PSL 5 mg. Though his condition remitted completely, his MPO-ANCA titers recently increased to above 600 EU once more. We conducted a follow-up renal biopsy to ascertain if the fluctuation of MPO-ANCA titers reflected an early stage of relapse. Light microscopic findings of the biopsied tissue revealed no signs of necrosis or crescentic formation of the glomeruli. Immunofluorescent microscopic findings were negative. The elevated MPO-ANCA titers were not valuable for the early prediction of relapse in our case, and the immune complex may have played an important role. When judging relapse and remission in ANCA-associated glomerulonephritis, it is important to evaluate the overall clinical findings and histopathological findings in addition to the serial ANCA titers.     

Long-Term Characteristics of 5-Year Survivors After Liver Resection for Colorectal Metastases

Background We investigated factors affecting 5-year survival in patients undergoing hepatic resection for colorectal cancer metastases, including events long after initial hepatectomy. Although retrospective studies have demonstrated survival benefit of hepatectomy for metastatic colorectal cancer, few have included sufficient 5-year survivors to identify survival-related factors throughout the clinical course. Methods We divided 156 patients with hepatectomy for colorectal cancer metastases into 5-year survivors (n = 64) and patients dying before 5 years after hepatectomy (n = 92). Clinicopathologic data were compared retrospectively with respect to long-term outcome. Results By multivariate analysis, large liver tumors (adjusted relative risk, 2.029; P = .011), short tumor doubling time (1.809; P = .026), and origin from poorly differentiated primary adenocarcinoma (12.632; P = .001) compromised survival, whereas initial treatment-related variables did not. Although no difference was seen in initial treatment-related variables between 5-year survivors with recurrence after hepatectomy and patients dying before 5 years, repeat surgery was used more frequently in survivors (P < .001), typically with adjuvant chemotherapy. Conclusions Reoperations for each recurrence of metastases, followed by additional chemotherapy, frequently resulted in long survival.     

C4d Immunohistochemistry in glomerulonephritis with different antibodies

Background The presence of C4d in the kidney is generally detected particularly for the diagnosis of antibody-mediated rejection in renal transplants. In frozen sections of immunofluorescence (IF) staining with anti-C4d monoclonal antibodies (mAbs), we noted intrinsic C4d deposition even in normal glomeruli though their pathogenic or an intrinsic role is unkown. An anti-C4d polyclonal antibody (C4dpAb), which is suitable for paraffin immunoperoxidase (IP) staining, is less used than mAbs, and it has demonstrated that intrinsic C4d is not evident. To establish a stable and reproducible procedure for C4d detection with the C4dpAb and to determine the staining characteristics of it, the present study aimed to test whether the method was comparable with IF with a mAb. Methods We compared the C4dpAb with the mAb in adjacent sections of human diseased kidneys, and then compared IP with IF of C4dpAb. Two ways of antigen retrieval was examined for IP. Results On comparing the two antibodies for glomerular staining with IF, we found that the pattern and intensity (C4dpAb showed intrinsic C4d with IF) were similar. In addition, C4dpAb staining with IP and IF demonstrated that the intrinsic staining in the normal glomerulus was mostly undetectable by IP, whereas IF showed distinct staining. Likewise, C4d deposition with IP in some cases was apparently weaker than that on IF, suggesting that this deposition is not intrinsic but indicates pathogenic complement activation. Conclusions The advantage of the C4dpAb for immunohistochemistry is of value for reconsidering the role of C4d in glomerular diseases.     

A phase II study of a THP-COP regimen for the treatment of elderly patients aged 70 years or older with diffuse large B-cell lymphoma

Pirarubicin (tetrahydropyranyl adriamycin: THP) is an anthracycline drug that reportedly has fewer cardiotoxic effects than doxorubicin. A phase II study was conducted in order to determine the efficacy of a treatment regimen incorporating THP, namely THP-COP in the treatment of elderly patients aged 70 years or older with diffuse large B-cell lymphoma (DLBCL). The treatment regimens for Group A (aged 70-79 years, n = 45) and Group B (aged 80 years or older, n = 16) consisted of cyclophosphamide, THP, vincristine, and prednisolone, repeated six times, every 3 weeks. The complete remission rate was 72.1%. The 5-year survival rate was 38.1%. For elderly patients with favourable prognostic factors, the 5-year survival rate was significantly better at 77.9% compared with 15.6% for patients with poor prognostic factors (p < 0.01). Death associated with the treatment regimen was not observed. We conclude that the THP-COP treatment regimen has fewer side effects and is very effective in the treatment of DLBCL in elderly patients, especially those with favourable prognostic factors. The present findings indicate the necessity of future studies investigating a combination therapy comprised of rituximab and THP-COP for the treatment of elderly patients with CD20-positive DLBCL.     

A Case of Cat Cry Syndrome Associated with Cleft Lip

Cat cry syndrome (cri-du-chat syndrome) is an extremely rare condition characterized by a high shrill cry during infancy, resulting from either the deletion of the short arm of chromosome 5 or unbalanced translocation inherited from a parent. We report the case of a 1-year-old girl with cat cry syndrome associated with cleft lip. The patient showed a ventricular septal defect, cleft lip, growth and mental retardation, micrognathia, ptosis of the eyelids, hypertelorism, epicanthal folds, and a preauricular tag on the right side. A chromosomal study revealed the terminal deletion of chromosome 5 (46, XX, del(p14.2)ish del(5)). Repair of the cleft lip was carried out concurrently with resection of the preauricular tag, and the patient's postoperative course was uneventful.     

A case of pancreatic serous cystadenoma with obstructive jaundice

A 62‐year‐old man with precordial pain and fever consulted a local practitioner. Blood tests revealed jaundice. Acute cholecystitis was diagnosed on ultrasonographic examination, and percutaneous transluminal gall‐bladder drainage was performed. The patient was referred to the Department of Surgery for operation. Imaging studies performed via a drain disclosed compression and stenosis of the lower portion of the common bile duct. A computed tomographic scan showed a multilocular nodule‐like low‐density area measuring 2.0 × 2.0 cm in diameter at the head of the pancreas. Endoscopic retrograde cholangiopancreatography disclosed compression and stenosis of the main pancreatic duct at the head of the pancreas. Angiographic examination revealed encasement of the intrapancreatic branch of the posterior pancreatic arcade, located in the same area as the compression stenosis of the bile duct. The results of imaging studies suggested cancer of the head of the pancreas, and a pancreatoduodenectomy was performed. The resected specimen included a mass measuring 3.5 × 2.7 × 1.7 cm, which was located at the head of the pancreas. On examination of a cut section, the mass was found to consist of small multilocular cysts. The cysts invaded the intrapancreatic bile duct. The histopathological diagnosis was serous cystadenoma.     

Inhibition of human platelet aggregation by -amino acid oxidase purified from Naja naja kaouthia venom

-Amino acid oxidase (LAO) widely exists in snake venoms. Purification of LAO from the Naja naja kaouthia (monocellate cobra) venom has been reported (Tan and Swaminathan, 1992), but its structural characterization and physiological function remained to be determined. The function of snake venom LAOs in hemostasis, especially their effect on platelet aggregation, has been controversial. We determined the N-terminal amino acid sequence of the N. n. kaouthia LAO named K–LAO to be DDRRSPLEECFQQNDYEEFLEIAKNGLKKTxNPKHVXxV (38 residues). The protein data base search revealed that the enzyme had high similarities with other snake venom LAOs. Further, platelet aggregation studies revealed that K–LAO functionally did not induce platelet aggregation in a platelet-rich plasma system, but that it inhibited platelet aggregation induced by agonists such as ADP, collagen and ristocetin in a dose-dependent manner. K–LAO diminished platelet aggregation more intensely under low than high shear stress. This inhibitory activity of K–LAO on either ristocetin-induced or shear-induced platelet aggregation was quenched by addition of catalase. These results indicate that K–LAO functions as an inhibitor to platelet aggregation through the formation of hydrogen peroxide. The enzyme may contribute to the development of a severe hematological disorder due to cobra envenomation.     

Effect of NaClO treatment on bonding to root canal dentin using a new evaluation method.

The purposes of this study were to investigate the reliability and efficiency of a new evaluation method for resin bonding to root canal dentin, which measures both marginal adaptation and shear bond strength simultaneously, and to determine the effects of root canal irrigants on resin bonding. A wet bonding system (Single Bond) and a self-etching primer system (Clearfil Mega Bond) were employed; NaClO was used as a root canal irrigant. No gaps or changes in bond strength were observed despite the NaClO treatment when the wet bonding system was employed, while the gap formation ratio increased, and bond strength decreased with longer NaClO treatment time when the self-etching primer system was employed. These findings suggested that this new experimental method was effective for evaluating resin systems to the root canal wall dentin which is affected by irrigation with NaClO.     

Streptococcal Pyrogenic Exotoxin F (SpeF) Causes Permeabilization of Lung Blood Vessels

Acute respiration distress syndrome (ARDS) is a typical complication in toxic shock-like syndrome (TSLS) caused by Streptococcus pyogenes. An isolated perfused rat lung model was used to identify the causative agent of ARDS in TSLS in this study. Some crude preparations separated from the culture supernatants of S. pyogenes isolates caused rapid increases in the weight of perfused lungs, indicating vascular permeabilization. Six samples from M type 1 and 3 isolates from TSLS and pharyngitis patients showed strong permeabilization activity, whereas preparations from isolates of other M types (although the number of isolates examined was limited) were negative. The active substance was purified to a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis using various columns, and the N-terminal amino acid sequence was determined. The resultant sequence of eight amino acids was identical to SpeF (mitogenic factor). Moreover, the vascular permeabilization activity of the purified band was abolished with anti-SpeF antiserum prepared by immunizing with the purified SpeF. This activity was also neutralized by the antiserum prepared by immunizing with a synthetic peptide derived from the published SpeF sequence. These results suggested that streptococcal SpeF is a major cause of permeabilization of lung blood vessels and sufficient for the pathogenesis of ARDS under the conditions of TSLS caused by S. pyogenes.