Expression of macrophage inflammatory protein-1α (MIP-1α) in human endometrium throughout the menstrual cycle

Objective To investigate the distribution and the role of macrophage inflammatory protein-la (MIP- 1α) in human endometrium during cyclic changes.
Setting Department of Obstetrics and Gynaecology, Shiga University of Medical Science and University Hospital.
Materials Eighteen endometrial tissue specimens surgically resected or biopsied from women with normal menstrual cycles, without hormonal disorder or endometrial diseases.
Methods By immunohistochemistry, using monoclonalantibodies (lambda delta 78 for MIP-la and CR3/43 for human leukocyte antigen-DR (HLA-DR)).
Results Immunoreactivity for anti-MIP-lα was distributed diffusely in epithelial cells throughout the proliferative and secretory phases but was absent during menstruation due to degenerative or necrotic changes. HLA-DR was expressed in epithelial cells only in the late secretory phase and was not expressed in stromal cells.
Conclusion Immunohistochemicalanalysis showed the presence of MIP- lα in the endometrial epithelium. Expression of HLA-DR in epithelial cells was observed only in the late secretory phase, suggesting that accumulation of MIP-lα in epithelium occurred by self production and not via a receptor mediated pathway. MIP-lα was released from the denuded epithelium during menstruation and appeared to contribute to the accumulation of monocytes/macrophages into the endometrial cavity. MIP-la has a number of biological effects other than monocytic chemotaxis, and some of these effects may be exerted in the endometrial tissue.     

Case of Gastric Lymphoma Diagnosed by Laparoscopic Excision Biopsy

Primary gastric lymphoma is a relatively uncommon disease and sometimes forms submucosal growth causing difficulty of diagnosis. We have reported a case of primary gastric lymphoma successfully diagnosed by laparoscopic wedge resection, after repeatedly performing endoscopic forcep biopsies. Diagnostic laparoscopy for obtaining definite histological diagnosis can be regarded as minimally invasive, accurate and safe.     

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cydooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer. (Cancer Sci 2003; 94: 355–359)     

Suppression of visually initiated hand movement by stimulation of the prefrontal cortex in the monkey

Five adult monkeys (Macaca fuscata) were trained for the go/no-go hand movement task with discrimination between two different color stimuli. The go stimulus was accompanied by a reward when a monkey lifted a lever by wrist extension within the stimulus duration (500 ms). Whereas the no-go stimulus was not. The monkey revealed the potential specific to the no-go response in the prefrontal cortex, called 'no-go potential', i.e. surface-negative, depth-positive deflexions in the cortex of the dorsal bank of the principal sulcus and of the rostroventral corner of the prefrontal region. Effects of electrical stimulation of these prefrontal areas upon the go response were observed and analyzed in order to study functional significances of the no-go potential. The surface and depth (2.0-3.0 mm) electrodes chronically implanted respectively in various cortical areas of both hemispheres, originally used for recording cortical field potentials, were utilized for bipolar stimulation of the cortical area. A train of brief electrical pulses was delivered to the loci producible of the no-go potential at different times after the onset of go visual stimulus. The stimulation suppressed the go movement by cancelling and delaying. The grade of the suppressor effect depended on the timing of electrical stimulation after the onset of visual stimulus, and was maximal at around the time of appearance of the no-go potential. The suppressor effect was compared with that produced by stimulating some other areas in the prefrontal cortex and the premotor cortex, and was found rather unique in those areas producible of the no-go potential.(ABSTRACT TRUNCATED AT 250 WORDS)     

Crosstalk between high-molecular-weight adiponectin and T-cadherin during liver fibrosis development in rats

Adiponectin, a circulating adipocyte-derived secretory protein, reportedly plays an important role in liver fibrosis development, although the biological role of adiponectin in liver fibrogenesis is still controversial. Adiponectin is present in the serum as three oligometric complexes; namely, high-, middle-, and low-molecular weight (HMW, MMW, and LMW, respectively). Adiponectin exerts different biological activities in an oligomerization-dependent manner. The aim of our current study was to examine the alteration of each isoform of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) during the choline-deficient L-amino acid-defined (CDAA) diet-induced rat liver fibrosis development. We also elucidated the methylation status of all receptors. The serum level of total adiponectin significantly increased during the liver fibrosis development. Among the three isoforms, only HMW adiponectin was significantly up-regulated whereas MMW and LMW were not. The expression of T-cadherin, which exclusively binds with HMW adiponectin, was significantly augmented as well. The AdipoR2 expression was markedly decreased and showed no marked difference from that of AdipoR1. No obvious methylation change was observed in all three receptors, suggesting that another mechanism is involved in the alteration of receptor gene expression. Collectively, since the specific ligand and receptor were augmented together, crosstalk between HMW adiponectin and T-cadherin may play an important role during liver fibrosis development in rats.     

pH-dependent translocation of alpha-tocopherol transfer protein (alpha-TTP) between hepatic cytosol and late endosomes

BACKGROUND: alpha-Tocopherol transfer protein (alpha-TTP), a member of the Sec14 protein family, plays an important role in transporting alpha-tocopherol, a major lipid-soluble anti-oxidant, in the cytosolic compartment of hepatocytes and is known as a product of the causative gene for familial isolated vitamin E deficiency. It has been shown that the secretion of hepatocyte alpha-tocopherol taken up with plasma lipoproteins is facilitated by alpha-TTP. To explore the mechanism of alpha-TTP mediated alpha-tocopherol secretion, we investigated drugs which may affect this secretion. RESULTS: We found that, in a hepatocyte cell culture system, intracellular alpha-tocopherol transport is impaired by chloroquine, an agent known for its function of elevating the pH in acidic compartments. Under chloroquine treatment, the diffuse cytosolic distribution of alpha-TTP changes to a punctate pattern. Double-staining experiments with endocytosis markers revealed that alpha-TTP accumulates transiently on the cytoplasmic surface of late endosomal membranes. This phenomenon is specific for hepatoma cell lines or primarily cultured hepatocytes. Other members of the Sec14 family, such as cellular retinaldehyde-binding protein (CRALBP) and supernatant protein factor (SPF), do not show this accumulation. Furthermore, we elucidate that the obligatory amino acid sequence for this function is located between amino acids 21 and 50, upstream of the N-terminal end of the lipid-binding domain. CONCLUSION: We hypothesize that a liver-specific target molecule for alpha-TTP exists on the late endosomal membrane surface. This transient binding may explain the mechanism of how alpha-tocopherol is transferred from late endosomes to cytosolic alpha-TTP.