Basket-weave structure in the stratum corneum is an important factor for maintaining the physiological properties of human skin as studied using reconstructed human epidermis and tape stripping of human cheek skin.

BACKGROUND: The normal stratum corneum (SC) has an upper basket-weave (BW) pattern layer and a lower compact layer. The transition from compact to BW SC is well associated with a transition from diffuse to peripheral distributions of corneodesmosomes (CDs). The loss of transition from compact SC to BW SC appears to cause structural and barrier-function impairments. OBJECTIVES: To show the involvement of the BW SC in maintaining the physiological properties of the skin. METHODS: Reconstructed human epidermis (RHE) with a complete BW structure was created by treatment with prepared emulsion-A, an oil-in-water emulsion. The RHE tissues were subjected to histological analysis, and the distribution of CDs on the SC with or without BW SC was analysed by anti-desmoglein (Dsg)1 antibody immunofluorescence and ultrastructural and Western blotting analyses. Ultrastructural analysis of intercellular lipids was performed. The mechanical properties of the RHE were evaluated. RESULTS: Emulsion-A successfully generated the BW SC in the RHE in which the degradation of CDs was promoted. The intercellular space of the BW SC generated by emulsion-A was filled with multilamellar lipid sheets. The softness of the SC with a BW structure formed with emulsion-A was higher than that of the compact SC in RHE. The outermost SC Dsg1 degradation (formation of the BW SC as determined with Dsg1 pixels) was correlated with water-barrier functions and the SC softness of healthy human cheek, which varied widely. CONCLUSIONS: Emulsion-A successfully generated the BW SC in RHE for the first time. This method is suggested to be a useful tool for investigating the physiological significance of the BW SC in vitro. Determination of Dsg1 content in the SC obtained by tape stripping from human skin allows study of the effects of external stimulants, such as creams and ointments, including cosmetics, on the completeness of the BW SC in situ without biopsy. What's already known about this topic? The normal stratum corneum (SC) has two layers, an upper basket-weave (BW) pattern layer and a lower compact layer. Epidermal diseases such as ichthyosis vulgaris and X-linked ichthyosis have an incomplete or no BW SC and impaired SC barrier functions, in which corneodesmosome (CD) degradation in a peripheral distribution is impaired. The roles of the BW SC in the physiological properties of human skin have not been clearly elucidated. What does this study add? Reconstructed human epidermis (RHE) with a complete BW structure was generated for the first time by treatment with oil-in-water emulsion-A. The formation of the BW SC was associated with a decrease in Dsg1 content, which represents the CD number in the SC. The intercellular space of the BW SC generated by emulsion-A, but not compact SC, was filled with multilamellar lipid sheets. The softness of the SC with a BW structure formed by emulsion-A treatment was higher than that of the compact SC in RHE. What is the translational message? RHE with a complete BW SC generated by emulsion-A treatment is suggested to be a useful tool for investigating effects on the physiological functions of the BW SC, as in treatments with creams and ointments including cosmetics. Determination of desmoglein 1 content in the SC obtained by tape stripping from human skin can make it possible to study the effects of external stimulants, such as creams and ointments, including cosmetics, on the completeness of the BW SC in situ without biopsy.

Efficacy and safety of voriconazole in the treatment of chronic pulmonary aspergillosis: experience in Japan.

BACKGROUND: Though various clinical conditions of aspergillosis can occur, depending essentially on the host's immunological status, the focus of research in North American and European countries has mainly been on invasive pulmonary aspergillosis in immunocompromised patients. There are, however, also many problems to overcome in chronic forms of aspergillosis. One of those problems is that there are no codified treatment guidelines for chronic pulmonary aspergillosis (CPA). Especially in Japan, this issue is more serious, because there are more cases with CPA due to the many aged people with past history of tuberculosis. Several clinical cases and case series have reported the usefulness of the various antifungal agents that are available. The new triazole, voriconazole, in particular, seems to be effective in the treatment of CPA. The aim of the present study is to evaluate the efficacy and safety of voriconazole in the treatment of CPA in non-immunocompromised patients. PATIENTS AND METHODS: We conducted a prospective, open-label, non-comparative, multicenter study over a 2-year period. For inclusion in the study, patients with confirmed or probable CPA were recruited in 11 hospitals of the National Hospital Organization in Japan. Clinical, radiological, serological, and mycological data were collected at baseline and 12 weeks after treatment or at the end of treatment. RESULTS: Among 77 patients enrolled in the study, 71 patients (mean age 65.9 years, 56 males and 15 females) were eligible for the study. All of the eligible patients presented with underlying lung diseases, including sequelae of tuberculosis (n = 35), non-tuberculous mycobacterial lung disease (n = 8), chronic obstructive pulmonary disease (COPD) (n = 8), interstitial pneumonia (n = 7), cystic lung disease (n = 4), pneumothorax (n = 3), bronchial cancer (n = 1), and others (n = 5). Voriconazole was indicated in 48 cases (68 %) as the first-line treatment for CPA and 23 patients previously received other antifungal therapies. Based on a composite of clinical, radiologic, serological, and mycologic criteria, good response was seen in 43 patients (60.6 %), no response was observed in 19 patients (26.8 %), and 4 cases (5.6 %) got worse. Five patients (7.0 %) were unassessable for efficacy. The common adverse events were visual disturbances (17 patients, 23.9 %), abnormal liver function test results (12 patients, 16.9 %), adverse psychological effects (3 patients, 4.2 %), and others (10 patients, 14.0 %). Treatment with voriconazole had to be stopped in 2 cases (2.8 %) because of serious adverse events (abnormal liver function test results). There was no association between adverse effects and trough voriconazole levels in serum. CONCLUSIONS: In Japan, voriconazole provides effective therapy of CPA in non-immunocompromised patients with an acceptable level of toxicity.

Monoclonal antibody to acetylcholine receptor: cell line established from thymus of patient with Myasthenia gravis.

A human B cell line producing a monoclonal antibody to an antigenic determinant of acetylcholine receptors was established by cloning B cells that had been transformed in vitro by Epstein-Barr virus. The B cells were obtained from the thymus of a patient with myasthenia gravis. The antibody produced by the cell line precipitated acetylcholine receptors from denervated and innervated rat muscle and from human muscle, but did not show detectable response to the acetylcholine receptors from the electric organs of Narke japonica. The monoclonal antibody showed identical binding patterns in innervated and denervated rat muscles. Passive transfer of the monoclonal antibody into rats induced moderate muscle weakness and electromyographic changes characteristic of myasthenia gravis.

Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems.

Glycyrrhiza uralensis roots used in this study were produced using novel cultivation systems, including artificial hydroponics and artificial hydroponic-field hybrid cultivation. The equivalency between G. uralensis root extracts produced by hydroponics and/or hybrid cultivation and a commercial Glycyrrhiza crude drug were evaluated for both safety and efficacy, and there were no significant differences in terms of mutagenicity on the Ames tests. The levels of cadmium and mercury in both hydroponic roots and crude drugs were less than the limit of quantitation. Arsenic levels were lower in all hydroponic roots than in the crude drug, whereas mean lead levels in the crude drug were not significantly different from those in the hydroponically cultivated G. uralensis roots. Both hydroponic and hybrid-cultivated root extracts showed antiallergic activities against contact hypersensitivity that were similar to those of the crude drug extracts. These study results suggest that hydroponic and hybrid-cultivated roots are equivalent in safety and efficacy to those of commercial crude drugs. Further studies are necessary before the roots are applicable as replacements for the currently available commercial crude drugs produced from wild plant resources.

Association between commensal bacteria and opportunistic pathogens in the dental plaque of elderly individuals.

Opportunistic infections in the oral cavity of the elderly may increase the incidence of systemic disease. The objective of this study was to investigate the differences in the oral bacterial flora between dependent elderly (inpatients) and independent elderly (community-dwelling residents). After multiple variables were taken into account, inpatients had significantly lower detection rates than community-dwelling residents for alpha-streptococci (p < 0.001) and Neisseria (p 0.004), and higher detection rates for Pseudomonas aeruginosa (p 0.024), methicillin-resistant Staphylococcus aureus (MRSA) (p 0.011) and Actinomyces spp. (p 0.005). Among inpatients, the requirement for a high degree of care was related negatively to detection of alpha-streptococci, but was related significantly to detection of P. aeruginosa (p 0.018) or MRSA (p 0.004). Tube-fed inpatients had a significantly lower detection rate for alpha-streptococci (p 0.041) and a higher detection rate for P. aeruginosa (p 0.004) than those who did not require tube feeding. Inpatients with a history of antibiotic use had a significantly lower detection rate for alpha-streptococci (p 0.049) and a higher detection rate for MRSA (p 0.007) than those without a history of antibiotic use. The detection rates for P. aeruginosa or MRSA in inpatients without alpha-streptococci were higher than in inpatients with alpha-streptococci after controlling for age and gender (P. aeruginosa, p 0.006; MRSA, p 0.001). Overall, detection of alpha-streptococci had an inverse correlation with the detection of P. aeruginosa and MRSA in the oral cavity and is likely to be an indicator of pathogenic bacterial infection.

Post-operative infection by pathogenic micro-organisms in the oral cavity of patients with prostatic carcinoma.

The aim of this study was to analyse the change in the oral cavity microflora of 14 patients who had undergone a radical prostatectomy for prostatic carcinoma. The detection of micro-organisms in the oral cavity was compared before and after the surgical procedure. Post-operative infection, defined as those patients who had increased Candida species counts and/or pathogenic bacteria only at the post-operative examination, was observed in 10 patients. Six patients showed increased Candida species counts at the post-operative examination compared with the pre-operative examination. In five patients, pathogenic bacterial species were detected at the post-operative examination but not at the pre-operative examination. One patient had detectable pathogenic bacterial species only at the post-operative examination along with increased Candida species counts. Our findings suggest that pre-operative oral hygiene to remove bacterial and Candida species from patients who are scheduled for surgical procedures is important for satisfactory clinical outcomes.

Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma.

Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis.

Prevalence and clinical significance of supra- or infraclavicular drainage on preoperative lymphoscintigraphy in women with breast cancer.

OBJECTIVE: Preoperative sentinel lymph node (SLN) mapping by lymphoscintigraphy is helpful to evaluate extra-axillary SLNs over a wider range than the blue dye method. However, the clinical value of extra-axillary SLNs remains uncertain. The goal of this study was to determine the prevalence and clinical significance of supra- or infraclavicular drainage on preoperative lymphoscintigraphy in women with breast cancer. MATERIALS AND METHODS: We retrospectively reviewed the files of 942 consecutive breast cancer women who underwent preoperative lymphoscintigraphy for SLN biopsy at our institution between April 2004 and March 2015. RESULTS: Supra- or infraclavicular drainage was detected in 5/942 women (0.5%) on preoperative lymphoscintigraphy. An axillary hot spot was detected in all five women, and a positive axillary SLN was detected in four women. Breast tumor locations were the upper inner or outer quadrants in four women and the lower outer quadrant in one woman. The median follow-up period was 75 months (mean: 92; range: 26-111 months). Recurrence outside the axilla was found in three (60%) women. The woman with a negative SLN status did not undergo adjuvant chemotherapy, but developed extra-axillary lymph node recurrence 3 years after primary surgery. No patient died of metastatic breast cancer at the last follow-up. CONCLUSIONS: The detection of the supra- or infraclavicular SLNs on lymphoscintigraphy may provide additional staging information to tailor individual treatment regimens with regard to the potential risk of recurrence or metastasis of breast cancer.

The difference in congenital cholesteatoma CT findings based on the type of mass.

OBJECTIVE: A retrospective assessment of differences in congenital cholesteatoma CT findings with a focus on type of cholesteatoma mass. MATERIALS AND METHODS: The medical records and CT images of 14 patients with congenital cholesteatomas in the middle ear who underwent surgery at our institution between January 2009 and July 2014 were reviewed. Cholesteatomas were classified as closed type, open type, or mixed type based on intraoperative findings. The CT findings including cholesteatoma size, location, and shape were retrospectively reviewed. RESULTS: Eight patients had closed type cholesteatomas, four had mixed type, and two had open type. The mean size of all cholesteatomas was 5.1mm. None of the cholesteatoma types indicated a tendency towards a certain location. The round shape was observed more frequently in closed type cholesteatomas than in other types (closed: 5/8; mixed: 1/4; open: 0/2). Two large closed type cholseteatomas and two mixed type cholesteatomas exhibited a constricted shape. Both of the open type cholesteatomas displayed an irregular shape. CONCLUSION: Small closed type congenital cholesteatomas were typically observed as round shaped lesions, but large closed type cholesteatomas and other type cholesteatomas tended to display shapes other than round.

Two-step mechanism of myofibrillar protein degradation in acute plasmocid-induced muscle necrosis.

Acute muscle necrosis was induced in rats by intramuscular injection of plasmocid, a known myotoxic agent. A single injection of 5 mg/ml plasmocid produced massive fiber necrosis with extensive phagocytosis. Plasmocid administration led to a preferential decrease of alpha-actinin with preservation of other structural proteins within 3 h after injection, and large increases (2-7-fold) in the activities of acid hydrolases, cathepsins B and L, cathepsin D and alpha-galactosidase within 48 h after injection. The plasmocid-induced stimulation of alpha-actinin loss seen at 3 h, when no increases of acid hydrolases occurred, could be inhibited by a cysteine protease inhibitor, Ep-475 (E-64-c), and EGTA. On the other hand, increased lysosomal enzyme activity seemed to have a close correlation with the appearance of invading mononuclear cells, probably macrophages, and not muscle lysosomes. These observations suggest that a two step mechanism of protein degradation (nonlysosomal and lysosomal processes) possibly occurs in plasmocid-induced muscle degradation and macrophages can serve as a main endogenous reservoir of proteases in pathological states.

Time dependent impairment of vagally mediated inhibition of noradrenaline release in the dog heart.

The effects of right vagal nerve stimulation on changes in heart rate, mean coronary sinus blood flow, and noradrenaline overflow rate induced by right cardiac sympathetic nerve stimulation were investigated in anaesthetised decentralised, open chest dogs, when autonomic nerve fibres were stimulated tonically at a frequency of 4 or 5 Hz for 2.5 min. Sympathetic nerve stimulation produced a mean(SEM) increase in each of the variables (50(7.0)% in heart rate, 48(6.3)% in coronary sinus blood flow, and 87.0(12.3) ng.min-1 in noradrenaline overflow rate into coronary sinus blood at 30 s), and the increments remained almost constant during continued stimulation. Vagal nerve stimulation induced a decrease of 34(3.4)% in heart rate and of 22(4.5)% in coronary sinus blood flow and a slight reduction (-9(3.2) ng.min-1) in noradrenaline overflow rate at 30 s. Only the decrease in heart rate faded slightly with time. Combined stimulation of the sympathetic and parasympathetic nerves induced a decrease of 19(5.0)% in heart rate and 4(7.5)% in coronary sinus blood flow and an increase of 34.3(12.0) ng.min-1 in noradrenaline overflow rate at 30 s. The decrease in heart rate and coronary sinus blood flow faded, and noradrenaline overflow rate increased significantly to 86.4(17.3) ng.min-1 at 120 s. The temporal changes in heart rate, coronary sinus blood flow, and noradrenaline overflow rate caused by combined nerve stimulation were readily inhibited by treatment with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Agouti signaling protein inhibits melanogenesis and the response of human melanocytes to alpha-melanotropin.

In mouse follicular melanocytes, the switch between eumelanin and pheomelanin synthesis is regulated by the extension locus, which encodes the melanocortin-1 receptor (MC1R) and the agouti locus, which encodes a novel paracrine-signaling molecule that inhibits binding of melanocortins to the MC1R. Human melanocytes express the MC1R and respond to melanotropins with increased proliferation and eumelanogenesis, but a potential role for the human homolog of agouti-signaling protein, ASIP, in human pigmentation has not been investigated. Here we report that ASIP blocked the binding of alpha-melanocyte-stimulating hormone (alpha-MSH) to the MC1R and inhibited the effects of alpha-MSH on human melanocytes. Treatment of human melanocytes with 1 nM-10 nM recombinant mouse or human ASIP blocked the stimulatory effects of alpha-MSH on cAMP accumulation, tyrosinase activity, and cell proliferation. In the absence of exogenous alpha-MSH, ASIP inhibited basal levels of tyrosinase activity and cell proliferation and reduced the level of immunoreactive tyrosinase-related protein-1 (TRP-1) without significantly altering the level of immunoreactive tyrosinase. In addition, ASIP blocked the stimulatory effects of forskolin or dibutyryl cAMP, agents that act downstream from the MC1R, on tyrosinase activity and cell proliferation. These results demonstrate that the functional relationship between the agouti and MC1R gene products is similar in mice and humans and suggest a potential physiologic role for ASIP in regulation of human pigmentation.

Expression of human papillomavirus type 6b E2 gene product with DNA-binding activity in insect (Bombyx mori) cells using a baculovirus expression vector.

Human papillomavirus type 6b (HPV6b) has been shown to be a major etiologic agent of genital condylomas. The E2 gene, one of the early genes, has been shown to activate the enhancer element in trans in cells transformed with bovine papillomavirus type 1a (BPV1a) but the E2 gene product of any HPV has not been identified. The E2 gene of HPV6b was inserted into the polyhedrin gene of a Baculovirus, Bombyx mori nuclear polyhedrosis virus (BmNPV), 156 bp downstream from the translational start codon, and transferred into BmNPV by allelic replacement in a cotransfected Bombyx mori cell line, Bm-N. The predicted 46-kDa protein was produced by a recombinant virus in the infected Bm-N cells at a high level under the control of the polyhedrin promoter. We obtained the antibody against the putative E2-polyhedrin fusion protein by immunizing a rabbit with this protein. This protein reacted with the antibodies against polyhedrin and the fusion protein. This protein did specifically bind to the upstream regulatory region of the HPV6b and BPV1a genomes. This DNA binding activity was blocked by the antibody against this protein.

Delta waves in the EEGs of patients with intracerebral hemorrhage.

Localized polymorphic delta wave activity appears ipsilaterally in patients with intracerebral hematoma without a shift of midline structures, regardless of the location of hematoma. Appearance of delta wave slowing after thalamic bleeding is quite variable, however, and may produce localized slowing or unilateral diffuse polymorphic delta wave activity. Unilateral diffuse polymorphic delta wave activity is seen in patients with larger hematomas of 30 mL or more, which cause a shift of the midline structures. The shift of midline structures, including the hypothalamus and surrounding structures, is thought to be one of the main factors responsible for the production of unilateral responsible for the production of unilateral diffuse polymorphic delta wave slowing.

Quantification of segmental wall motion by length-based Fourier analysis.

A new method for evaluating segmental wall motion by length-based Fourier analysis is described. Fourier analysis is performed on a series of lengths from a center to edges of the ventricle, generating parameters of percent length shortening (%LS) and phase of the segment (length-based phase). The reproducibility of the result was good, since the algorithm was automatic except for the setting of the ventricular region as a mask image to exclude surrounding blood pools. This program can be applied for quantification of ventricular wall-motion abnormalities in gated blood-pool studies, and for analysis of the timing of ventricular contraction in gated blood-pool emission computed tomography to detect the site of an accessory conduction pathway in patients with Wolff-Parkinson-White syndrome.

Phase analysis in the Wolff-Parkinson-White syndrome with surgically proven accessory conduction pathways: concise communication.

Twenty-one patients with the Wolff-Parkinson-White (WPW) syndrome who underwent surgical division of the accessory conduction pathway (ACP) were studied by gated blood-pool scintigraphy. In each case, a functional image of the phase was generated, based on the fundamental frequency of the Fourier transform. The location of the ACP was confirmed by electrophysiologic study, epicardial mapping, and surgery. Phase analysis identified the side of preexcitation correctly in 16 out of 20 patients with WPW syndrome with a delta wave. All patients with right-cardiac type (N = 9) had initial contraction in the right ventricle (RV). In patients with left-cardiac type (N = 10), six had initial movement in the left ventricle (LV); but in the other four the ACPs in the anterior or lateral wall of the left ventricle (LV) could not be detected. In patients with multiple ACPs (N = 2), one right-cardiac type had initial contraction in the RV, while in the other (with an intermittent WPW syndrome) the ACP was not detected. These observations indicate that abnormal wall motion is associated with the conduction anomalies of the WPW syndrome. We conclude that phase analysis can correctly identify the side of initial contraction in the WPW syndrome before and after surgery. However, as a method of pre-operative study, it seems difficult to determine the precise site of the ACP by phase analysis alone.

Expression of the E2 open reading frame of papillomaviruses BPV1 and HPV6b in silkworm by a baculovirus vector.

To produce and characterize the nature of the E2 protein of papillomaviruses, we have developed a system to express the DNA sequence containing an open reading frame (ORF) as a fusion protein in cultured insect cells and silkworms. The DNA fragments of the E2 ORF predicted from the DNA sequence of bovine papillomavirus type 1 and human papillomavirus type 6b were linked to the N-terminal part of polyhedrin gene of the Baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) vector. Hybrid proteins composed of polyhedrin protein (52 amino acids) and the E2 proteins of BPV1 (410 amino acids) or HPV6b (346 amino acids) were efficiently produced in B. mori cells and silkworm larvae infected with recombinant viruses. The amount of E2 fusion proteins produced by recombinant viruses was comparable to that of polyhedrin produced by wild type BmNPV. The hybrid proteins were immunologically reactive to antiserum against polyhedrin.

Transforming growth factor beta1 increases the expressions of high molecular weight tropomyosin isoforms and vinculin and suppresses the transformed phenotypes in human lung carcinoma cells.

Exposure of the human lung carcinoma cell line, A549 cells, to transforming growth factor beta1 (TGFbeta1) resulted in an alteration in the morphology from epithelial-like to fibroblastic flat cells. Immunofluorescent study revealed that microfilament organization was partially restored in the TGFbeta1-treated cells. We also investigated the effects of TGFbeta1 on the transformed phenotypes including the anchorage-independent growth and invasive ability of A549 cells and found that the phenotypes were strikingly suppressed in TGFbeta1-treated A549 cells. Accompanying these changes, the levels of the expression of high molecular weight tropomyosin (TM) isoforms, especially TM1 and TM2, were significantly increased in the TGFbeta1-treated cells. The expression level of vinculin was also increased in these cells. These results suggest that the increased tropomyosin and vinculin syntheses may be involved in the suppression of the transformed phenotypes of A549 cells.

Quantification of two aromatic amine mutagens, PBTA-1 and PBTA-2, in the yodo river system.

The levels of two aromatic amine mutagens, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-am ino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino-4-[N-(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5-a mino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), were quantitatively analyzed in the Yodo River system in Japan. The river water samples were collected at nine sampling sites from the Yodo River system twice or three times between May and July in 1997. PBTA-1 and PBTA-2 in the river water samples were concentrated on blue rayon columns, partially purified by high-performance liquid chromatography (HPLC) on reverse-phase columns, then quantified by HPLC with an electrochemical detector. The amounts of PBTA-1 and PBTA-2 in the water samples were < 0.01-1.91 and < 0.01-2.25 ng/L, respectively. High levels of PBTA-1 and PBTA-2 were detected in the samples collected within 4 km downstream of two sewage plants, which are located along the banks of the Nishitakase River, a tributary of the Yodo River system, and these samples showed stronger mutagenicity in Salmonella typhimurium YG1024 with S9 mix than the other water samples. On the other hand, the river water samples from upstream of the sewage plant were weakly or not mutagenic and PBTA-1 and PBTA-2 were not detected. These results confirmed that a major source of PBTA-1 and PBTA-2 in the Yodo River system is effluent from the sewage plants and that discharged mutagens, including PBTA-1 and PBTA-2, are diluted and/or decomposed while moving down the Yodo River system.

Crescentic glomerulonephritis developing 3 months after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A 64-year-old woman underwent an ileocecal resection for ileus. The specimen revealed a diffuse large B cell lymphoma. The diagnosis was stage IIA non-Hodgkin's lymphoma. She received chemotherapy with the CHOP-etoposide regimen, resulting in partial remission. High-dose etoposide was used for PBSC mobilization before auto-PBSCT. Conditioning was ranimustine, carboplatin, etoposide and cyclophosphamide. Her renal function deteriorated gradually, starting 3 months post-PBSCT. Eight months post-transplant, serum creatine concentration was 7.1 mg/dl, and BUN was 59.2 mg/dl. Her hemoglobin concentration decreased to 5.3 g/dl, with no evidence of hemolysis. Renal biopsy revealed fibrous crescent formations in glomeruli, and mononuclear cell infiltration in interstitial spaces. Renal injury in this patient differs from BMT nephropathy, which is similar to hemolytic uremic syndrome, and represents another type of late renal injury after PBSCT.