Max protein expression is associated with survival of children with lymphoblastic lymphoma

Overexpression of c-Myc in murine B lineage cells is associated with a polyclonal pre-B cell expansion as well as development of pre-B or B lymphoblastic lymphoma (LL) accompanied by leukemia, which mirrors the clinical features of childhood LL. Of interest, Max overexpression attenuates aberrant growth of B cells triggered by c-Myc. However, the clinical significance of Max in human lymphoid tissue remains to be clarified. In the present studies, we studied the expression of the c-Myc and Max proteins in normal lymph nodes and in childhood LL. In normal lymph nodes, c-Myc protein was expressed by the majority of cells in germinal center and marginal zone, but Max protein was expressed only by some of them. In contrast, c-Myc and Max were absent in mantle zone. Cells positive for c-Myc and Max expression in LL were 70.6 +/- 19.8% and 47.3 +/- 32.4%, respectively, determined by immunohistochemical staining using paraffin blocks from 23 cases of childhood LL. The survival of children with LL showing higher Max expression (> or = 30%) was significantly greater than that of lower expression (< 30%; P = 0.0027 using the Mantel-Cox test). These results suggest that Max protein may affect prognosis of childhood LL.     

Relation between distribution of viral RNA and development of histopathological changes in encephalomyocarditis virus-induced orchitis in mice

The relation between the distribution of viral RNA and the development of histopathological changes was investigated in the early stage of encephalomyocarditis (EMC) virus-induced orchitis in mice. Signals of viral RNA were first detected by in situ hybridization in a few Sertoli cells in almost intact germinal epithelia at 2 days post-inoculation (d.p.i.). The number of Sertoli cells bearing signals of viral RNA increased at 3 d.p.i. when mild degenerative changes were exceptionally found in germinal epithelia. Signals of viral RNA came to be detected not only in Sertoli cells but also in a small number of germinal cells and spermatogonia at 4 d.p.i. when mild to moderate degenerative changes developed in germinal epithelia, resulting in desquamation of degenerated cells. At the same time, virus-like particles were observed by electron-microscopy in the degenerated and desquamated germinal cells. At and after 5 d.p.i., luminal obstruction with cellular debris and inflammatory cells was generally found. These results suggest that EMC virus carried to seminiferous tubules via the blood first attacks Sertoli cells and then damages germinal cells and spermatogonia.     

A Case of Pseudomyxoma Peritonei with Bilateral Pleural Metastases

A case of pseudomyxoma peritonei that was first recognized bydyspnea and abnormal shadows on chest X-ray film is reported.The patient is a 67-yr-old woman who was found to have an abnormalshadow on chest X-ray filni on routine physical examinationwhen she was 47 yr old (1960). She had been asymptoniatic untilabout 2 yr before admission when she began to experience dyspneawith increased severity. On admission, the chest X-ray filmand com puted tomography showed bilateral pleural thickening.Drainage and decortica tion was carried out, and multiple cystsfilled with a gelatinous substance were found bilaterally inthe thoracic cavity. On the 66th hospital day, pan- peritonitisfollowing perforation of the appendix occurred and an emergencyoperation was performed. The patient died of acute renal failureon the 13th postoperative day. Pseudomyxoma peritonei originatingfrom pseudomucinous cystadenocarcinoma of the appendix was diagnosedon the basis of the findings of the histopathological examination.At autopsy, the gelatinous substance was found in both pleuralcavities, the right subphrenic area, and part of the large omentum.The case presented here is a very rare case of pseudomyxoniaperitonei, because dyspnea was the main feature and abdominalsymptoms such as abdominal distension and pain were lacking.Then high level of serum carcinoenibryonic antigen seen in thiscase is also pointed out.     

IN VITRO (EX VIVO) EXPANSION OF MURINE HEMATOPOIETIC STEM CELLS Running Title: In Vitro Expansion of Stem Cells

Currently there is significant interest in in vitro (ex vivo) expansion of human hematopoietic stem and progenitor cells in hematology and oncology. Transplantation of umbilical cord blood stem cells promises to be a new and exciting mode of bone marrow/stem cell transplantation since it is inexpensive and appears to be associated with milder graft vs. host disease (GVHD) than transplantation of adult cells. A potential problem of cord blood transplantation is the limited number of stem cells that may be harvested. The majority of cases of cord blood transplantation, therefore, have been attempted in children. If it were possible to expand the population of stem cells in umbilical cord blood and transplant them to adult recipients, it would significantly enlarge the scope of this form of transplantation. Already many preclinical studies have shown that it is possible to expand the population of total cells and progenitors in culture in the presence of combinations of cytokines. Whether or not it is possible to expand the population of hematopoietic stem cells which have long-term reconstitution capabilities remains to be clarified (1–3). The cytokines used in the majority of attempts of in vitro expansion were selected from a group of early-acting cytokines such as steel factor (SF, kit ligand), flt3 ligand (FL), interleukin (IL)-3, IL-6, IL-11, granulocyte/ macrophage-colony stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF). The rationale for combining these cytokines has been explained in a recent review (4). Almost all protocols for in vitro expansion include IL-3 and many contain IL-1 because of their known myelopoietic effects.     

In Vitro Biological Activity of an Insulin-like Active Substance Extracted from the Tumor Tissue of a Patient with Primary Liver Cell Carcinoma Associated with Severe Spontaneous Hypoglycemia

Biological activity of an insulin-like active substance, extractedfrom the tissue of a tumor tissue of a patient with primaryliver cell carcinoma associated with severe spontaneous hypoglycemia,was studied in vitro. The substance was acid insoluble. It stimulatedglucose uptake and glucose oxidation by rat muscle and adiposetissue, and these effects were not suppressed by anti-insulinantibody. It stimulated glycogen synthesis in rat muscle tissuebut not in adipose tissue. Oxidation of glucose C-1 by adiposetissue was enhanced strongly by the substance, but it had noeffect on glucose C-6 oxidation. The biological activity ofthe substance resembled that of non-suppressible insulin-likeactivity-precipitated (NSILA-P) rather than that of pancreaticinsulin or nonsuppressible insulin-like activity-soluble (NSILA-S).     

Maximum tumor diameter is a simple and valuable index associated with the local extent of disease in clinically localized prostate cancer

BACKGROUND: The present study was undertaken to investigate the association of pathological features, including the total tumor volume (TTV), maximum tumor area (MTA), and maximum tumor diameter (MTD), with the local extent of disease in clinically localized prostate cancer. METHODS: Serial whole sections of the prostate from 164 patients who underwent radical prostatectomy for localized prostate cancer were investigated. The correlations between the indicators of tumor size, including the TTV, MTA, and MTD, and other pathological parameters were evaluated. RESULTS: The MTD, MTA, and TTV were significantly correlated with each other. Multivariate stepwise logistic regression analysis indicated that the Gleason score, perineural invasion, microvascular invasion, and MTD were significant independent parameters associated with extraprostatic disease. CONCLUSION: The histological tumor grade, perineural invasion, microvascular invasion, and tumor size were correlated with the local extent of disease. The MTD, a simple, easy, and inexpensive parameter, is a more significant pathological feature associated with the local extent of disease than the MTA or TTV.     

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 × 10⁴ plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system.