Estrogen receptors in human myeloma cells.

It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells, we investigated the mRNA expression levels of estrogen receptor (ER)-alpha, ER-beta, and coactivators and corepressors in nine human myeloma cell lines and compared them with those of seven human breast cancer cell lines including four ER-positive and three ER-negative lines. The alterations in cell growth and mRNA expression of the target genes of ER or those of cytokines in the myeloma lines by estradiol or antiestrogens (tamoxifen and toremifene) were also investigated.

Over-expression of the decoy receptor 3 (DcR3) gene in peripheral blood mononuclear cells (PBMC) derived from silicosis patients.

Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, is considered to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Recently, a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds FasL and inhibits FasL-induced apoptosis, has been identified. Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities.

Serum levels of soluble Fas ligand in patients with silicosis.

Certain patients with silicosis have been reported to exhibit immunological abnormalities such as the appearance of antinuclear antibodies and the occurrence of autoimmune diseases. Fas ligand (FasL) is a type II membrane protein which induces apoptosis by binding to its membrane receptor, Fas. FasL is converted to a soluble form by a metalloproteinase-like enzyme.

Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32. 3) and FGFR3 translocation.

Recently several chromosomal translocations involved in myeloma cases and myeloma cell lines; i.e., t(11;14)(q13;q32), t('8;14)(q24;q32), t(4;14)(q16.

Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B.

The aim of this study was to investigate whether man-made mineral fibers (MMMF) induce apoptosis of human peripheral blood mononuclear cells (PBMC), as we recently demonstrated for chrysotile B. In vitro cultivation of PBMC with various MMMF as well as chrysotile B clearly produced apoptotic cells. The alteration of the expression for apoptosis related genes at the mRNA level during in vitro cultures of PBMC with various MMMF revealed upregulation of Flice and Apaf-1 genes and down regulation of TNF receptor 1 and Bid genes.

Glial expression of fibroblast growth factor-9 in rat central nervous system.

We examined the expression of fibroblast growth factor (FGF)-9 in the rat central nervous system (CNS) by immunohistochemistry and in situ hybridization studies. FGF-9 immunoreactivity was conspicuous in motor neurons of the spinal cord, Purkinje cells, and neurons in the hippocampus and cerebral cortex. In addition to the neuronal localization of FGF-9 immunoreactivity that we reported previously, the present double-label immunohistochemistry clearly demonstrated that the immunoreactivity was present in glial fibrillary acidic protein (GFAP)-positive astrocytes preferentially present in the white matter of spinal cord and brainstem of adult rats and in CNPase-positive oligodendrocytes that were arranged between the fasciculi of nerve fibers in cerebellar white matter and corpus callosum of both adult and young rats.

Evaluation of cases with silicosis using the parameters related to Fas-mediated apoptosis.

To establish a new clinical index for immunological abnormalities occurring in silicosis, several clinical parameters related to Fas-mediated apoptosis; i.e., membrane Fas expression on peripheral blood lymphocytes (mFas), serum soluble Fas levels (sFas), serum soluble Fas ligand levels (sFasL), and soluble/membrane Fas mRNA expression ratios (s/mFas ExR) in peripheral blood mononuclear cells (PBMC) were investigated.

5-HT(2A/2C) receptor agonist-induced increase in urinary isatin excretion in rats: reversal by both diazepam and dexamethasone.

Isatin, a stress-related biological substance, increases in rat urine in association with elevated catecholamine biosynthesis during stress. The goal of this study was to unravel how the biosynthetic pathway of isatin is related to stress response. The importance of the serotonergic compounds in anxiety, which is the major emotional process of stress response, has emerged.

Genetic association between alpha-2 macroglobulin and Japanese sporadic Alzheimer's disease.

Alpha-2 macroglobulin (encoded by the gene A2M) is a serum pan-protease inhibitor that may be related with the pathogenesis of Alzheimer's disease (AD) because of its ability to mediate amyloid beta degradation. Recently, several groups have reported that the five-nucleotides deletion in A2M gene at the 5' splice site of exon 18 might increase risk for AD. In the present study, therefore, this mutation was studied in 69 healthy controls and 55 sporadic AD cases by polymerase chain reaction- restriction fragment length polymorphism method.

[A follow-up study on the outcome and relevant factors in senile dementia of Alzheimer type and vascular dementia].

We followed 126 patients with senile dementia of Alzheimer type (SDAT), and 129 over age 65 with vascular dementia (VD) who were diagnosed at the Center for Elderly Dementia in our institution between February 1990 and February 1993. At 5-year follow-up, 62 patients with SDAT and 71 patients with VD had died. These patients were assessed prospectively to investigate the neuropsychiatric and somatic factors related to the prognosis of SDAT and VD.

FGF-9 is an autocrine/paracrine neurotrophic substance for spinal motoneurons.

Motoneurons need muscle-derived neurotrophic substances for their survival during the initial phase of their development, but after maturation they lose this requirement and can survive after axotomy. This suggests that some neurotrophic substances other than target-derived ones control the survival of motoneurons in adults. Because spinal motoneurons express fibroblast growth factor-9 (FGF-9) messenger RNA, we hypothesized that FGF-9 might be an autocrine or paracrine survival factor for motoneurons.

Reinforcement enhances hippocampal acetylcholine release in rats: an in vivo microdialysis study.

Rats were trained to press a lever under a 'Multiple FI-60s and Extinction' schedule with food reinforcements. After learning the task, an in vivo microdialysis probe was inserted into the dentate gyrus and CA3 regions of the hippocampus, and the sequential changes in the dialysate acetylcholine (ACh) concentration were analyzed. In the session, two fixed-interval of reinforcement (FI) components (for 20 min) and two extinction (EXT) components (for 30 min) were alternated to examine the correlation between behavioral and neurochemical outcomes.

Bleomycin hydrolase immunoreactivity in senile plaque in the brains of patients with Alzheimer's disease.

Bleomycin hydrolase (BH), a cysteine protease belonging to the papain superfamily, is one of the candidate beta secretases. We performed immunohistochemical studies of Alzheimer's disease (AD) brains using an antibody to BH. Polyclonal antibody to BH immunostained neocortical neurons.

Fibroblast growth factor (FGF)-9 immunoreactivity in senile plaques.

We examined fibroblast growth factor (FGF)-9 immunoreactivity in human hippocampal sections of Alzheimer's disease (AD). FGF-9 immunoreactivity was observed in dystrophic neurites of senile plaques in AD and control cases, in addition to the hippocampal and cortical neurons. The amyloid core and neurofibrillary tangles lacked immunoreactivity.

Human myeloma cell apoptosis induced by interferon-alpha.

Although there have been reports regarding the clinical effectiveness of IFN alpha in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy-carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour-cell apoptosis, particularly in immunological prevention.

Stress-induced increase in urinary isatin excretion in rats: reversal by both dexamethasone and alpha-methyl-P-tyrosine.

The effects of acute food deprivation and acute cold exposure on 24-hr urinary isatin excretion in rats and a mechanism responsible for changes in urinary isatin excretion during stress were investigated. This is the first study to demonstrate by HPLC that urinary isatin excretion is increased by stress. Both types of stress induced a marked increase in urinary isatin excretion during the 24 hr following the initiation of stress.

Soluble Fas mRNA is dominantly expressed in cases with silicosis.

Although it is well known that cases with silicosis exhibit various immunological abnormalities, the mechanisms involved in the occurrence of immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule that is involved in the apoptosis pathway that belongs to the tumour necrosis factor-receptor family. Soluble Fas (sFas) is produced as an alternatively spliced product of the Fas gene and protects cells from apoptosis due to antagonization of the binding between membrane form of the Fas gene (mFas) and the Fas ligand.

In vitro excess ammonia production in human myeloma cell lines.

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells.

Effect of the nitrosourea anti-tumor chemotherapeutical agent MCNU on five human myeloma cell lines.

We investigated the effects of MCNU (methyl-6)3-(2-chloroethyl)-3-nitrosoureido)-6-deoxy- alpha-D-glucopyranoside), a nitrosourea anti-tumor agent developed in Japan, on cell growth and differentiation in five human myeloma cell lines and compared it with relative expression levels of MDR-1 gene. Although 10 microg/ml of MCNU inhibited cell growth in KMM-1 and KMS-5 lines, other three cell lines required 20-40 microg/ml of MCNU to obtain similar growth inhibition. Accumulation up to the G2 phase of the cell cycle was observed in KMM-1 and KMS-5 lines and the cloning efficiency of KMS-5 cells was reduced by MCNU.

Establishment and characterization of a new human testicular seminoma cell line, JKT-1.

Background: A new human testicular cancer cell line (JKT-1) was established, successfully transplanted into nude mice, and has been maintained for over 2 years. We examined the biological characteristics of JKT-1 cells.

Methods: The original material for JKT-1 was derived from a primary lesion of a left testicular seminoma (pure, typical-type) from a 40-year-old male.

Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease.

Tyrosine hydroxylase (TH) gene is the rate-limiting enzyme in the synthesis of catecholamines. Functional polymorphisms of the TH gene may be involved in the pathogenesis of neuropsychiatric diseases such as schizophrenia, affective disorders, and Parkinsonism. This study examined a possible association of two polymorphisms, both of which result in an amino acid change of the TH protein, with schizophrenia and Parkinson's disease (PD).