Clonal evolution from trisomy into tetrasomy of chromosome 8 associated with the development of acute myeloid leukemia from myelodysplastic syndrome

Tetrasomy 8, though rare, is usually associated with trisomy 8, a far more common chromosomal abnormality in acute myeloid leukemia (AML). Yet the clonal relationship between trisomy 8 and tetrasomy 8 in the cases with these chromosomal abnormalities has been unclear. Here, we report a case of a 17-year-old male, diagnosed as having a myelodysplastic syndrome (MDS). Chromosome analysis showed the presence of trisomy 8. Five years later, he developed overt AML exhibiting tetrasomy 8 only. After chemotherapy, the blast cells in the bone marrow decreased to 3.4%, and the karyotype showed trisomy 8 alone. Fluorescence in situ hybridization using a probe specific for chromosome 8 showed that the percentages of cells exhibiting 2/ 3 /4 signals were 7.8/89.2/2.0 at the MDS stage, 20.5/36.1/41.0 when overt AML developed and 24.0/72.1/2.4 after chemotherapy. These results suggested that tetrasomy 8 is derived from the AML clone, possibly evolved from the MDS clone with trisomy 8. To our knowledge, this is the first detailed case report of clonal evolution from trisomy 8 into tetrasomy 8 associated with the development of AML from MDS.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Parvalbumin in rat cerebrum, cerebellum and retina during postnatal development

Radioimmunoassay and immunohistochemical studies were performed on the occurrence and distribution of parvalbumin-like immunoreactivity (PA-LI) in developing rat cerebrum, cerebellum and retina. No PA-LI was detected in the nervous tissues of the newborn animals. In the cerebrum, the PA-LI appeared in non-pyramidal neurons at the 2nd postnatal week and increased linearly until the 8th week. In the cerebellum, a rapid increase in the PA-LI took place at the 2nd week, with an enrichment of the antigen to Purkinje neurons. In the retina, amacrine cells contained PA-LI, the levels of which increased from the 2nd to 4th week. Regulation of intracellular Ca²⁺ concentration may be one of the important factors for the maturation of the central nervous system.     

Relation between yawning behavior and central serotonergic neuronal system in rats

Summary Subcutaneously (s.c.) administered apomorphine (0.0125–0.4 mg/kg) or physostigmine (0.025–0.4 mg/kg) to rats elicited yawning. The dose-response curves were bellshaped. The peak effects of apomorphine and physostigmine were observed with a dose of 0.1 mg/kg of each drug. Yawning elicited by apomorphine (0.1 mg/kg) or physostigmine (0.1 mg/kg) was reduced by intraperitoneally (i.p.) administered 5-hydroxytryptophan (5-HTP, 50–200 mg/kg, given 30 min before). Yawning elicited by apomorphine but not by physostigmine was enhanced by p-chlorophenylalanine (p-CPA, 25–400 mg/kg i.p., given 24 h before). Apomorphine elicited but not physostigmine-elicited yawning was enhanced by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 8 g/rat, given 14 days before into the dorsal raphe). This treatment led to a 35% depletion of serotonin (5-HT) in the striatum. 5-HTP, p-CPA or 5,7-DHT given alone did not elicit yawning. Bilateral, intrastriatal microinjection of apomorphine (1.5 –50 g/site) but not physostigmine (5–50 g/site) elicited yawning. The dose-response curve was also bell-shaped. These results indicate that central serotonergic pathways play an important role in modulating drug-elicited yawning in rats. Send offprint requests to S. Okuyama at the above address     

A single-strip mini-paper chromatographic method for rapid purity-control of 99mTc-labeled radiopharmaceuticals

A single-strip miniaturized paper chromatographic method (Mini-PC) was developed using 80%–90% acetone solvent for rapid purity-control of ^99mTc-radiopharmaceuticals. Routine ^99mTc-radiopharmaceuticals (eight kinds of kit made agents) and diluted agents (in which radiochemical impurities might be formed) were analyzed by Mini-PC and other methods. This showed that, compared with the other methods, the Mini-PC technique is useful for the simple and rapid routine analysis of radiochemical impurities of kit made ^99mTc-radiopharmaceuticals.     

Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient’s condition.     

Histopathological explanation of the MRI target sign in extra-axial schwannomas

BackgroundTo better understand the nature of magnetic resonance imaging (MRI) findings in schwannomas, especially in the “target sign” of these findings, the histopathological investigation was performed.MethodsThe MRI findings were correlated with histopathological features in 22 samples of schwannomas, which were mostly resected from the extremities. The histopathological analyses included alcian blue staining and immunohistochemical staining for S-100 protein, proliferating cell nuclear antigen (PCNA) and epithelial membrane antigen (EMA).ResultsSeven of the 22 samples of schwannomas of the extremities exhibited target signs including a peripheral zone of homogeneously high signal intensity and a central zone of heterogeneous signal intensity in T2-weighted images. Gadolinium-enhanced T1–weighted images demonstrated a central heterogeneous enhancement and a peripheral ring of homogeneously low signal intensity. Histopathologically, S-100 and PCNA were positive only in the central heterogeneous signal area. In contrast, EMA was only stained on the degenerative epi/perineurium in the peripheral zone.ConclusionIn schwannomas of the extremities showing target sign in T2-weighted images, histopathologically, the peripheral areas were suggested to be mucinous degeneration of the epineurium or perineurium, while the central areas were composed of truly neoplastic cells.     

Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study

Clinical and Experimental Nephrology - A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis...     

Photoreceptor differentiation of retinoblastoma: An electron microscopic study of 29 retinoblastomas

Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.1 months and the tumor cells showing photo-receptor differentiation were demonstrated in 10 cases (35%). The findings were especially notable in retinoblastomas with Flexner-Wintersteiner rosette formation (seven cases, 28%). Similar photoreceptor differentiation was also evident in solid cell clusters without rosette formation (four cases, 14%). The presence of photoreceptor elements was assumed to be significantly frequent both in Flexner-Wintersteiner rosettes and in the solid cell clusters. The cell cytoplasm also showed proliferation of long mitochondria and microtubules, reflecting photoreceptor differentiation. The hereditary-type retinoblastoma showed more advanced cell differentiation than the non-hereditary type. Photoreceptor differentiated retinoblastoma showed rather indolent growth compared with the undifferentiated type, and the former can expect a curative treatment by operation. These observations provide additional findings of the biological nature of retinoblastomas.