Serum lipids and lipoprotein lipids were studied in 53 patients (21 males and 32 females) with xanthelasma palpebrarum and 40 age-matched normal controls (20 males and 20 females). Patients were subdivided into patients with normolipidemia, hyperlipidemia or familial hypercholesterolemia (FH). In both male and female patients with hyperlipidemia or FH, the serum cholesterol (Chol) levels were significantly higher than in normal controls. In both male and female patients with normolipidemia or hyperlipidemia, the VLDL-Chol levels were significantly higher than in normal controls. Male patients with FH showed significantly higher levels of VLDL-Chol than normal controls. Both male and female patients with normolipidemia, hyperlipidemia or FH showed significantly higher levels of LDL-Chol, lower HDL-Chol levels and lower HDL-Chol/LDL-Chol ratios than normal controls. In both male and female patients with hyperlipidemia and in male patients with FH, the serum triglyceride (TG) levels were significantly higher than in normal controls. Both male and female hyperlipidemic patients showed significantly higher levels of VLDL-TG than normal controls. In male patients with FH, the VLDL-TG levels were significantly above the control levels. In male patients with normolipidermia, the LDL-TG levels were significantly higher than in normal controls. In both male and female patients with hyperlipidemia or FH, the LDL-TG levels were significantly higher than in normal controls. The HDL-TG levels in patients with normolipidemia (males) or FH (females) were significantly lower than in normal controls. The prevalence of coronary heart disease in patients with normolipidemia, hyperlipidemia or FH was 29.4%, 24.0% and 45.4%, respectively.

Adult↗

PubMedDate not supplied

Clinicopathologic study of primary mediastinal non-lymphoblastic non-Hodgkin's lymphomas among the Japanese.

We studied the morphologic, immunologic and clinical features of 14 cases of primary non-lymphoblastic non-Hodgkin's lymphomas of the mediastinum. The patients ranged in age from 3 to 76 years, with a median age of 28 years. According to the Ann Arbor classification, 71% of our cases were in an early stage. Three cases were in Stage I, eight in Stage II, one in Stage III and two in Stage IV (one with multiple hepatic lesions and another with bone marrow involvement). The patients were heterogeneous in terms of the disease and were therefore histologically classified into three categories: diffuse large B cell lymphoma with sclerosis (DLS; n = 8); large cell anaplastic lymphoma (LC-Ana; n = 5); and low grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma; n = 1). DLS was the most common group and was characterized as CD5-, CD10-, CD19+, CD20+, CD21- and CD22+. Imprint smears showed azurophilic granules in the cytoplasm of the tumor cells of three of four DLS cases. All of the six cases examined were negative when tested for Epstein-Barr virus (EBV) sequences after hybridization with the EBV internal repeat probe. DLS and MALT lymphoma cases were of a B-lineage lymphoma of the thymus, while most of the LC-Ana cases were of a T-lineage lymphoma. Patients with non-lymphoblastic non-Hodgkin's lymphomas had a relatively favorable prognosis compared with lymphoblastic lymphoma (P < 0.01 by the generalized Wilcoxon test). There was no significant difference in the survival between non-lymphoblastic non-Hodgkin's lymphoma and Hodgkin's disease (P > 0.05 by the generalized Wilcoxon test).

Adolescent↗

PubMedDate not supplied

Brain malformations caused by retroviral vector-mediated gene transfer of hippocampal cholinergic neurostimulating peptide precursor protein into the CNS via embryonic mice ventricles.

Hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp) is a unique multifunctional protein, being not only the precursor of HCNP, which promotes the phenotype development of septo-hippocampal cholinergic neurons, but also the binding protein of phosphatidylethanolamine, ATP, Raf-1 kinase (known as "Raf-1 kinase inhibitory factor" in peripheral organs), and serine protease. We obtained a high-titer retroviral vector harboring HCNP-pp cDNA by the use of a modified packaging cell line and centrifugation, and by injecting it into embryonic mouse ventricles, we investigated the function of its gene product within the central nervous system (CNS). We found that efficient transduction into hippocampal pyramidal neurons can be achieved by injecting the vector into embryonic brain ventricles on embryonic day 14 (E14). Three days after receiving the intraventricular injection of the high-titer HCNP-pp retrovirus vector on E14, the tissues around the ventricles showed an overexpression of HCNP-pp. This was accompanied by a reduced amount of activated MEK and Erk (as analyzed by histochemical and Western blot methods), suggesting that HCNP-pp also regulates the MAP-kinase cascade within the CNS. Surprisingly, mouse brains that received the HCNP-pp retroviral vector showed massive malformation of the hippocampus and cerebellum when examined 30 days after birth. This shows that strictly regulated HCNP-pp gene expression is necessary for the normal development of the mouse brain, and that the moderate overexpression achieved by retroviral vector-mediated gene transfer is sufficient to cause severe abnormality of entire brain structures.

Animals↗

PubMedDate not supplied

[RNA-interference, induced by transient and continuous expression of hairpin RNA in cells from Drosophila and mammals].

RNA interference (RNAi) may be induced by a plasmid with an inverted repeat (IR) sequence directing transcription of hairpin-type double-stranded RNA (dsRNA). This study examines the effects of changing various parameters of IR constructs on Drosophila and mammalian RNAi, using the dual luciferase system, RNAi activity was found to vary depending on IR length ass well as the length and sequence of the internal loop separating sense and antisense sequences. Both transient and stable RNAi occurred in Drosophila cultured cells. Although transient DNA-mediated RNAi was noted in most mammalian cells, no mammalian cells stably possessing IR sequences and hence RNAi activity could be obtained. In Drosophila, DNA-mediated RNAi was considerably weaker than long-dsRNA-mediated RNAi. The cytological data indicated that this was most probably caused by abortive processing of hairpin RNA produced within cells. DNA-mediated RNAi was examined at the level of Drosophila individuals using extramacrochaetae as a model gene, and the presence of an intron sequence in the single-stranded loop region was shown to be essential for effective RNAi.

Animals↗

PubMedDate not supplied

Effect of treatment schedule on antitumor activity of glycolate-0,0'-diammineplatinum(II), a new platinum derivative: comparison with cis-diamminedichloroplatinum(II).

The effect of treatment schedule on the antitumor activity of a new platinum derivative, glycolate-0,0'-diammineplatinum (II) (254S) compared with cis- diamminedichloroplatinum (II) (CDDP) was investigated using ascites L1210 leukemia and solid Lewis lung carcinoma. The drugs were given i.p. by three treatments: as a single injection, as three injections at 4 day intervals and as 9 daily continuous injections. 254S produced a marked increase of lifespan in mice by all three treatment schedules (about 100% ILS), although the consecutive treatment of 254S needed more total doses against L1210 leukemia. The antitumor activity of 254S was, however, inferior to that of CDDP. Moreover, 254S did not show certain dependence on treatment schedule, while CDDP was rather dependent on treatment schedule. The single injection (day 1) of CDDP exhibited the most potent antitumor activity. On the other hand, although the single injection of CDDP showed more host toxicity than the other treatment schedules and the consecutive treatment needed more total doses, neither drug showed any definite schedule dependency against Lewis lung carcinoma. Moreover, the tumor growth inhibitory activity of 254S was almost the same as or slightly superior to that of CDDP. Both drugs produced about 70% (days 14-17) and 50% (day 20) tumor weight inhibitions against early and advanced Lewis lung carcinoma, respectively.

Animals↗

PubMedDate not supplied

Introduction of the c-kit gene leads to growth suppression of a breast cancer cell line, MCF-7.

Normal ductal cells of the breast are exceptional on that their epithelial cells abundantly express the c-kit receptor. Loss of c-kit expression has been reported in 80-90% of breast cancer specimens, suggesting a possible role in the development of tumors. In the present study, we introduced a c-kit expression vector into a breast cancer cell line. MCF-7, which does not express c-kit but does express its ligand, stem cell factor (SCF). Anchorage dependent and independent growth was found to be inhibited in bulk cultures of the c-kit transfectants, although this suppression appeared to be incomplete, allowing a considerable fraction to tolerate c-kit expression. Heterogeneous sensitivity to the suppressive effects mediated by the c-kit receptor was also observed among individual clones isolated from the bulk cultures. These results suggest that c-kit can mediate inhibitory signals for the growth of breast cancer cells, but that cellular heterogeneity exists regarding the response. Further studies are warranted to elucidate the molecular basis for the inhibitory effects of c-kit.

Animals↗