Perfluoroalkyl substances in waters along the Grand Canal, China.

The Grand Canal, also known as the Beijing-Hangzhou Grand Canal, is a UNESCO World Heritage Site and the longest canal in the world. It is an important trunk line of the South-to-North Water Diversion Project in China. The contamination status and spatial distributions of perfluoroalky substances (PFASs) in waters of the Grand Canal were investigated. The total concentrations of PFASs (∑PFASs) range from 7.8 ng/L to 218.0 ng/L, with high ∑PFASs occurring in the southern part of the Grand Canal which is located in a highly urbanized and economically developed region. The dominance of PFOA showed a decreasing trend toward north while shorter chain homologue proportions increased in the northern part of the Canal which mainly traverses underdeveloped and rural areas in Eastern China. Positive correlations were observed between ∑PFASs and the population density as well as GDP per capita. Intersection with large rivers may affect the contamination levels and composition of PFASs in the water of the Grand Canal near the intersection sites.

Particle size specific distribution of perfluoro alkyl substances in atmospheric particulate matter in Asian cities.

Seasonal and local characteristics of perfluorinated alkylated substances (PFASs) were examined using size-segregated particles including an ultrafine range. The examination included sampling and analysis of ambient particles collected at four sites located in different environments in three different countries, Japan (Kanazawa and Okinawa), Hong Kong and India. To minimize the evaporation artefacts derived from PFASs during the sampling, an air sampler that permitted particles smaller than 0.1 µm (PM0.1) to be separated at a moderate pressure drop (<5-15 kPa), was used for all of the air sampling procedures. In the case of Kanazawa, a local city in Japan, the concentration of PFASs was found to be dominated by carboxylates, especially PFOA, PFNA and PFDA regardless of the particle size and sampling period. Ultrafine particles were found to be the largest contributor to the mass fraction of PFCAs, while the maximum PFOS mass fractions were determined to be in the coarse-sized fractions. The seasonal difference in the total PFAS concentration can be largely attributed to precipitation. The results were basically similar for all sites that were examined. The type of land use may be a more influencing factor on the mass fraction of the PFASs than the country of origin. The dependency of PFAS mass fraction on the specific surface of the particle suggests that ultrafine PFAS particles are segregated, not only by gas deposition but could also be segregated by a mechanism involving compositional dependence or the primary source of the particles. Other possible sources of PFASs, other than from traffic are also possible.

Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma.

INTRODUCTION: The prognostic value of serum ferritin level in patients with peripheral T-cell lymphoma (PTCL) remains unknown. METHODS: We retrospectively analyzed clinical data from 78 consecutive patients with newly diagnosed PTCL that were treated with anthracycline-containing regimens between 1998 and 2011. RESULTS: The patients consisted of 50 males and 28 females with a median age of 64 years (range, 16-83 years). The subtypes of PTCL were 39 PTCL, not otherwise specified and 39 angioimmunoblastic T-cell lymphoma (AITL). The median observation period for the surviving patients was 50 months. The overall survival (OS) was poorer in patients with serum ferritin level above the upper normal limit (n = 28), compared with patients with serum ferritin level within normal range (n = 50; 4-year OS: 23% vs. 72%; P < 0.001). In the multivariate analysis, poor performance status (P = 0.006) and elevated serum ferritin level (P = 0.018) were independent risk factors for poor OS. CONCLUSION: Serum ferritin level is a useful prognostic marker for PTCL.

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy.

This prospective study aimed to investigate the influence of pretransplant serum ferritin levels on the outcomes of allogeneic hematopoietic SCT (HSCT). In total, 190 patients with acute leukemia or myelodysplastic syndrome were consecutively enrolled. The patients were divided into two groups: low-ferritin group (<1000 ng/mL) and high-ferritin group (⩾1000 ng/mL). The primary end point was the cumulative incidence of infection within 100 days after HSCT, which was similar between the two groups: bloodstream infection, 35 vs 38%, P=0.65; bacterial infection, 44 vs 41%, P=0.68; and fungal infection, 6 vs 8%, P=0.71. The 1-year adjusted probability of OS of the high-ferritin group was significantly lower than that of the low-ferritin group (76 vs 63%, P=0.017). Using receiver operating characteristic curve, the threshold of pretransplant serum ferritin levels for bloodstream infection was 1400 ng/mL; the threshold for OS, EFS and non-relapse mortality was 1349 ng/mL. In conclusion, pretransplant serum ferritin levels of ⩾1000 ng/mL did not influence the incidence of infection but adversely affected OS after HSCT. A higher threshold of pretransplant serum ferritin levels may predict HSCT outcomes.

Adjuvant radiotherapy to an initial bulky mass in diffuse large B-cell lymphoma: lack of survival benefit.

The role of adjuvant radiotherapy to the site of the initial bulky mass in lymphoma remains to be determined. We retrospectively analyzed clinical data for 35 consecutive patients with diffuse large B-cell lymphoma who had an initial bulky mass were treated successfully by chemotherapy reaching complete remission or complete remission unconfirmed according to International Workshop Criteria. Median age was 57 years. Median follow-up period for surviving patients after completion of chemotherapy was 45 months. Twenty patients (group A) received adjuvant radiotherapy to the bulky mass, while 15 (group B) did not. Median dose of radiation in group A was 40 Gy (range, 30-60 Gy). In group A, four relapses occurred, all from other sites; group B included three relapses from bulky and one from other sites. Overall survival (P = 0.15) and recurrence-free survival (P = 0.48) did not differ significantly between groups. Although adjuvant radiotherapy to the initial bulky site is useful for controlling local disease, no survival benefit was seen.

Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.

In all, 18 patients (30-56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.

Subcutaneous extramedullary hematopoiesis in a patient with secondary myelofibrosis following polycythemia vera.

We describe the case of a 73-year-old woman with secondary myelofibrosis who developed subcutaneous extramedullary hematopoiesis. Although extramedullary hematopoiesis has been generally observed in primary myelofibrosis, in this case it was seen in myelofibrosis secondary to polycythemia vera. Histological examination of the subcutaneous nodule revealed that the lesion included cells from the myeloid and megakaryocytic series. The skin lesion almost disappeared after treatment with hydroxyurea. We report here this rare manifestation in secondary myelofibrosis including a review of literature.

[Complete cytogenetic response obtained with unrelated donor lymphocyte infusion for relapse of chronic myeloid leukemia in blastic crisis after allogeneic bone marrow transplantation].

A 35-year-old man with chronic myeloid leukemia (CML) in blastic crisis (BC) received an allogeneic bone marrow transplant from an unrelated donor in October 1998 after three cycles of chemotherapy. BC relapse developed on day 349 after transplantation. After one cycle of chemotherapy and treatment with interferon, the patient received donor lymphocyte infusion (DLI), and this resulted in a complete cytogenetic response 21 days later. Grade III acute graft-versus-host disease developed on day 25 after DLI, but this was resolved after administration of prednisolone. Disease relapse occurred at extramedullary sites on day 162 after DLI, and the patient died of sepsis after receiving chemotherapy. This case illustrates that unrelated DLI can induce remission successfully in patients with relapse of CML in BC through a graft-versus-leukemia effect.

[Sequential analysis of p210- and p190-bcr-abl by RT-PCR after allogeneic bone marrow transplantation for p210/p190-bcr-abl double positive acute lymphoblastic leukemia].

In patients with both p210-bcr-abl (p210) and p190-bcr-abl (p190)-positive acute lymphoblastic leukemia, the number of p190 transcripts is lower than that of p210 transcripts. It is speculated that the p190 transcript occurs as a consequence of alternative splicing or missplicing events in the BCR gene. Four patients with both p210- and p190-positive acute lymphoblastic leukemia were studied for expression of p210 and p190 by RT-PCR before and after allogeneic bone marrow transplantation. p190 negativity was documented in all four patients, followed by p210 negativity one to two months later in three patients. These results suggest that negativity for p190 indicates an ongoing decrease in the small number of residual leukemic cells. In one patient p190 appeared transiently in spite of prolonged negativity for p210 18 months after bone marrow transplantation. We conclude that analysis of p210 and p190 is useful for following up patients with both p210- and p190-positive acute lymphoblastic leukemia.

[Twenty-one cases of Sebastian platelet syndrome].

We report a Japanese family with Sebastian platelet syndrome. Twenty-one thrombocytopenic patients exhibited giant platelets and inclusion bodies in their granulocytes. They were thought to be related because they bore the same surname and lived within a localized area. None of them had additional clinical findings peculiar to Fechtner syndrome. Ultrastructural studies of the granulocytes were performed on four patients. The inclusion bodies in the granulocytes were different from those found in May-Hegglin anomaly, and consisted of ribosome clusters and rough endoplasmic reticula.

[Acute myelocytic leukemia with ins(21;8)(q22;q13q22) presenting with AML1/MTG8 chimeric mRNA].

We report a case of acute myelocytic leukemia (AML) showing a chromosomal abnormality, ins(21;8), with AML1/MTG8 chimeric mRNA. The patient, a 73-year-old woman, was admitted to our hospital because of AML relapse. Bone marrow aspiration showed 44% blasts and ins(21;8)(q12;q13q22) by cytogenetic study. Moreover, the size of chimeric AML1/MTG8 mRNA detected by RT-PCR in this case was shorter than that of previously reported. The patient was diagnosed as having relapse of AML (M2), but achieved complete remission with DCP therapy. Four months later, extramedullary relapse occurred, and this was followed five months later by bone marrow relapse. However, the patient again achieved complete remission. Most cases of AML1/MTG8 fusion gene are caused by t(8;21), and only very rarely by ins(21;8). In this case, the AML1/MTG8 fusion gene is thought to have been involved in the onset of leukemia.

[Treatment outcome in elderly patients with aggressive non-Hodgkin's lymphoma].

Seventy-one patients aged 61-84 years with previously untreated aggressive non-Hodgkin's lymphoma were treated with a doxorubicin-containing regimen and evaluated retrospectively. The patients comprised 49 men and 22 women with a median age of 68 years. The median observation period was 544 days. Histological examination revealed 17 cases of diffuse small cleaved, 11 cases of diffuse mixed, 40 cases of diffuse large, and 3 cases of immunoblastic lymphoma, classified according to the International Working Formulation. When the patients were divided according to the age-adjusted international index, group A (61-64 years; n = 21) comprised 5 low (L)-, 4 low-intermediate (LI)-, 7 high-intermediate (HI)-, and 5 high (H)-risk patients. The corresponding numbers in group B (> or = 65 years; n = 50) were 14, 12, 16, and 8, respectively. The overall three-year survival rate was 50%, being 78% in group A and 36% in group B (P = 0.02), and 77% for L + LI patients and 34% for HI + H patients (P = 0.003). The respective three-year survival rates for L + LI and HI + H patients were 100% and 67% in group A, and 68% and 16% in group B. HI + H patients in group B showed shorter survival than L + LI patients in group B (P = 0.002) and HI + H patients in group A (P = 0.03). The cause of death in most group B HI + H patients was lymphoma, although the dose intensity of doxorubicin, cyclophosphamide and vincristine did not differ significantly from that in the other groups. Thus, HI + H patients aged 65 and over had an essentially poor prognosis.

Cutaneous monomorphous CD4- and CD56-positive large-cell lymphoma.

BACKGROUND: Recently, CD56 (NCAM)-positive lymphomas, such as nasal and nasal-type angiocentric NK/T cell lymphoma, aggressive NK cell leukemia/lymphoma and blastic NK cell lymphoma, were described by several authors as a unique group of lymphoma. OBJECTIVE: In this study, we intend to clarify the clinicopathological features of cutaneous CD4+ and CD56+ lymphoma. METHODS: Four patients with cutaneous CD4+ and CD56+ lymphoma were studied. RESULTS: Age at the first examination ranged from 71 to 89 years (mean = 81.2 years). One patient was female and 3 were males. The organ mainly involved at presentation was the skin. Lymphadenopathy, splenomegaly, leukemic spread and central nervous system involvement were observed as the disease progressed. The mean survival time was 12.2 months. Epstein-Barr virus was not detected within the tumor cells. CONCLUSION: This peculiar lymphoma is different from nasal and nasal-type angiocentric NK/T cell lymphoma and aggressive NK cell leukemia/lymphoma. Similar cases have been reported as blastic NK cell lymphoma/leukemia.

Chronic myelomonocytic leukemia with t(1;3)(p36;q21) and a synchronous gastric cancer.

The translocation t(1;3)(p36;q21) has been reported previously in patients with the myelodysplastic syndrome and with acute nonlymphocytic leukemia. It has been reported in only 5 cases of chronic myelomonocytic leukemia and t(1;3)(p36;q21). We observed a case of chronic myelomonocytic leukemia with t(1;3)(p36;q21) complicated by a gastric cancer at the time of diagnosis.

Anomalous substituent effects in the bischler-napieralski reaction of 2-aryl aromatic formamides

Treatment of some 1-naphthylformamides (or formanilides) possessing a 2,4,5-trioxygenated phenyl substituent at the 2-position with POCl(3) caused an unprecedented carbon insertion reaction into a benzene ring, producing 7-5 ring (azaazulene) systems as valence isomers of isoquinoline skeletons. Precise examination of this abnormal Bischler-Napieralski reaction (BNR) using various substrates led to the following scope and limitations: (i) the 7-5 ring systems were constructed when either 2-alkoxy-4, 5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a starting substrate; (ii) in the former case the formyl carbon was inserted into the C(1)-C(6) bond of the 2-phenyl group, and normal isoquinoline cyclization competed with an abnormal carbon insertion reaction; (iii) the presence of a hydroxy group at the 2'-position as in the latter cases caused exclusive carbon insertion, in which alternative C(1)-C(2) insertion products were quantitatively formed; (iv) 3, 6-dimethoxy-2-hydroxyphenyl-substituted formanilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produced an indole-pyrone as an abnormal BNR product. Theoretical approaches using the PM-3 method indicated that these abnormal BNRs could be triggered by ipso attack at the 1'-position yielding spiro intermediates. Ring cleavege of the six-membered ring in the spiro intermediates to a ketene function followed by recyclization was proposed for the 2'-hydroxy-directed abnormal BNRs leading to the C(1)-C(2) insertion product or the indole-pyrone derivative.

The effect of trihexyphenidyl, an anticholinergic agent, on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease.

Cerebral blood flow and oxygen metabolism were studied in six previously untreated patients with Parkinson's disease (PD) before and after anticholinergic treatment using positron emission tomography (PET) and compared with six controls. The PET study and an assessment of the disability and cognitive impairment were performed before and after administration of 6 mg trihexyphenidyl for 5 to 11 weeks. All PD patients showed improvements in motor symptoms after the trihexyphenidyl treatment. Cognitive function did not significantly differ between before and after trihexyphenidyl treatment. However, after trihexyphenidyl treatment, rCBF and rCMRO2 decreased by 15% in the striatum and by 10% in all cortical areas contralateral to predominantly symptomatic limbs, and by 10% in the ipsilateral striatum and all cortical areas, significantly below the values of controls in most cerebral cortices and striatum. These findings suggest that trihexyphenidyl inhibits the cortical cholinergic system and significantly decreases rCBF and rCMRO2 in the cerebral cortices without cognitive impairment in untreated patients with PD.

Characterization of a novel monoclonal antibody that senses nitric oxide-dependent activation of soluble guanylate cyclase.

Two monoclonal antibodies (mAbs) against bovine lung soluble guanylate cyclase (sGC) were prepared and characterized. mAb 3221 recognized both the alpha- and beta-subunits of sGC and had greater binding affinity to the enzyme in the presence of NO. mAb 28131 recognized only the beta-subunit and its affinity did not change with NO. Neither mAb cross-reacted with particulate GC. Cultured Purkinje cells from rats were treated with S-nitroso-N-acetylpenicillamine, an NO donor, and examined by immunocytochemical methods. The immunoreactivity associated with mAb 3221 increased with the cGMP content in a crude extract of cerebellum and the NO2 generated in the culture medium increased.

Intranasal administration of demopressin (DDAVP) for type 1 and type 2A von Willebrand disease.

Desmopressin was administered intranasally to seven patients with von Willebrand disease (type 1: 4 patients, type 2A: 3 patients) to assess the response and safety. von Willebrand factor antigen ranged from 8% to 60% before treatment and increased significantly after intranasal DDAVP administration (the median relative increase: two- to threefold). Factor VIII levels also increased substantially over baseline levels after intranasal administration. Before treatment ristocetin cofactor activity was 32 +/- 12% in patients with type 1 vWD and 9 +/- 5% in patients with type 2A vWD. After intranasal administration, the levels of ristocetin cofactor activity increased to 56 +/- 21% and 29 +/- 9%, respectively. The bleeding time was normalized in 86% of the patients. The abnormality of vWF multimers in type 1 vWD returned more or less to normal after intranasal DDAVP administration whereas that in type 2A vWD did not. The intranasal administration of DDAVP is safe and effective for minor bleeding episodes and is adaptable for home use in patients with type 1 and type 2A vWD.