Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks.

γ-Aminobutyric acid (GABA) is a kind of amino acid contained in green tea leaves and other foods. Several reports have shown that GABA might affect brain protein synthesis, improve many brain functions such as memory and study capability, lower the blood pressure of spontaneously hypertensive rats, and may also have a relaxation effect in humans. However, the evidence for its mood-improving function is still not sufficient. In this study, we investigated how the oral intake of GABA influences human adults psychologically and physiologically under a condition of mental stress. Sixty-three adults (28 males, 35 females) participated in a randomized, single blind, placebo-controlled, crossover-designed study over two experiment days. Capsules containing 100 mg of GABA or dextrin as a placebo were used as test samples. The results showed that EEG activities including alpha band and beta band brain waves decreased depending on the mental stress task loads, and the condition of 30 min after GABA intake diminished this decrease compared with the placebo condition. That is to say, GABA might have alleviated the stress induced by the mental tasks. This effect also corresponded with the results of the POMS scores.

A primary retroperitoneal serous cystadenocarcinoma with clinically aggressive behavior.

CASE REPORT: We describe a 44-year-old woman with a primary retroperitoneal serous cystadenocarcinoma as the fourth report in the world literature. A contrast-enhanced computed tomographic scan of the abdomen demonstrated a mass with enhanced solid mural nodules and septa in the left retroperitoneum. Serum CA19-9 was elevated at 181 U/ml. The patient underwent a complete resection of the retroperitoneal tumor with a partial resection of the psoas major muscle and its fascia. Pathological examination showed a well-differentiated papillary serous cystadenocarcinoma of ovarian type and locoregional lymph node metastases. Seven months after surgery, the patient developed a pelvic recurrence, and underwent a total hysterectomy, a left salpingo-oophorectomy and a resection of the metastatic mesenteric mass. Two months after the second surgery, serum CA19-9 and CA125 increased to 1,114 U/ml and 218 U/ml, respectively. A solitary liver metastasis was confirmed on a computed tomographic scan. The patient is now being treated with weekly docetaxel and carboplatin. CONCLUSION: The present case illustrates the clinically aggressive nature of a primary retroperitoneal serous cystadenocarcinoma.

Ossifying luteinized thecoma of the ovary.

A 51-year-old woman presented with lumbar backache leading to the preoperative diagnosis of a right solid adnexal mass with calcification on computed tomographic scan. Histological examination revealed a right ovarian luteinized thecoma characterized by extensive calcification and metaplastic ossification. Osteoblasts and osteoclasts surrounded the surface of the heterotopic bone. Haversian canals were occasionally identified in the bony trabeculae. Ossifying ovarian neoplasms are extremely rare and this case is the first to demonstrate the osseous metaplasia in ovarian luteinized thecoma.

Focal enhancement of expression of c-Met/hepatocyte growth factor receptor in the myocardium in human myocardial infarction.

To determine the distribution and expression level of hepatocyte growth factor (HGF) specific receptor, c-Met, in human myocardial infarction. Autopsies of 13 patients who died without heart diseases (control) and 13 patients with a history of myocardial infarction (2 h to 10 years before death). The harvested myocardial tissues were stained with hematoxylin-eosin (H&E) and immunohistochemically stained for c-Met expression by the avidin-biotin-horseradish peroxidase complex method using an antibody to c-Met. C-Met expression was only slightly increased in control subjects and in noninfarcted myocardium of the test group. In contrast, high expression was noted in the peripheral region of the myocardial infarction and in some hypertrophic myocardial cells. C-Met was not expressed in the infarcted myocardium, but overexpression was noted in the surrounding myocardial cells of blood vessels and in the subendocardium and subepicardium in a band-like pattern. The expression level of c-Met was most enhanced at the time of appearance of coagulative necrosis and least in the myocardium of subjects with old infarcts. Our results indicate that HGF preferentially reaches the ischemic regions of the myocardium and has local and direct effects on the myocardium in patients with myocardial infarction.

Extensive myocardial stunning showing transient regression of prolonged T wave inversion and prolonged sympathetic denervation.

A 69-year-old woman was admitted to the hospital with palpitations. Although left ventriculography showed extensive akinesis except in the basal hyperkinetic segment, coronary angiography showed normal coronary arteries. 123I-metaiodobenzylguanidine (MIBG) accumulation was obviously reduced in the anteroseptal, apical and inferior areas. Inverted T waves developed on day 3 and disappeared on day 104 after transient regression. Echocardiography showed normal left ventricular motion two weeks later. Ergonovine provocation test showed no vasospasm and thallium-201 showed no perfusion defect on day 46. Electrocardiography and MIBG returned to normal on day 216. These findings suggest prolonged sympathetic nerve injury in extensive myocardial stunning.

A simultaneous assay method for L-glutamate and L-pyroglutamate contents in soy sauce using a 5-oxoprolinase (without ATP hydrolyzing activity).

L-Glutamine and L-glutamate, which are important flavor components in soy sauce, are converted to L-pyroglutamate during brewing. Therefore, it is necessary that the L-glutamate and L-pyroglutamate contents can be measured accurately. We developed a simultaneous assay method for L-glutamate and L-pyroglutamate by using 5-oxoprolinase (without ATP hydrolyzing activity) and glutamate oxidase. By this method, the L-pyroglutamate could be measured accurately in a range of 0.05 to 1.0 mM in the presence of 1.0 mM L-glutamate. This system is effective for process and quality controls.

Co-expression of p53 and bcl-2 may correlate to the presence of epstein-barr virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) has been well documented in the aetiology of nasopharyngeal carcinoma (NPC), although its role as well as the genetic basis in the genesis of NPC have not been elucidated. The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2 oncoprotein, has been reported in a high percentage of cases, and also in association with EBV. Proliferating cell nuclear antigen (PCNA) has also been shown to be increased in NPC, suggesting its association among the overexpression of p53 and bcl-2 oncoprotein. We undertook this study to evaluate the correlation among these abnormalities in the development of NPC. The expression of p53 protein, bcl-2 oncoprotein, and the level of PCNA were investigated by immunohistochemistry in 53 patients with NPC. Twenty tissue samples from these patients were studied for p53 gene mutations by single strand conformation polymorphism (SSCP) and DNA sequencing as well as EBV genomes by polymerase chain reaction. Among the 53 specimens, 42 (79%) showed expression of p53 protein and 40 (75%) gave positive result for bcl-2 oncoprotein. A significant association was found between p53 expression and bcl-2 oncoprotein (P=0.002; Fisher's exact test) with 68% of the patients showing coexpression of both markers. The PCNA labelling index in the 53 patients varied from 5% to 80%. High PCNA labelling index was frequently found in the patients with overexpression of p53 protein and bcl-2 oncoprotein. The PCNA index in patients with p53 expression was significant higher than in those without p53 expression (P=0.002). Of the 20 patients, p53 mutations were found in four cases. EBV genomes were detected in 14 cases of which 12 cases showed overexpression of both p53 and bcl-2 and one case with only p53 expression and one case with bcl-2 expression. EBV genomes were detected in two cases with p53 mutations. We conclude that EBV is the important etiologic factor in NPC which may be involved in p53 and bcl-2 overexpression. The mutant p53 protein is correlated to deregulation of PCNA. p53 mutations participate in a small proportion of the tumorigenesis.

The role of S100A4 gene encoding an S100-related calcium-binding protein in human bile duct adenocarcinoma cell lines: correlation of S100A4 expression and invasive growth in Matrigel Matrix.

S100A4, one of the tandemly arranged S100 genes at chromosome 1q21, has been suggested to play a functional role in cell motility and invasiveness of tumor cell growth. We investigated the expression of S100A4 and the in vitro invasiveness of 4 human bile duct adenocarcinoma cell lines by the Matrigel assay. S100A4 was abundantly expressed in 2 adenocarcinoma cell lines whose growth pattern was highly invasive. Induction of antisense S100A4 into one of the cell lines decreased S100A4 mRNA levels and reduced invasiveness. In contrast, induction of sense S100A4 expression into non-invasive KMBC adenocarcinoma cells, which originally lacked S100A4 expression, resulted in apparent invasive potential in the transfected cells compared with the cells with the vector alone. These results suggest that S100A4 expression is well correlated with the invasiveness of human bile duct adenocarcinomas.

Molecular cloning, sequencing, and expression in Escherichia coli of the gene encoding a novel 5-oxoprolinase without ATP-hydrolyzing activity from Alcaligenes faecalis N-38A.

The gene encoding a novel 5-oxoprolinase without ATP-hydrolyzing activity from Alcaligenes faecalis N-38A was cloned and characterized. The coding region of this gene is 1,299 bp long. The predicted primary protein is composed of 433 amino acid residues, with a 31-amino-acid signal peptide. The mature protein is composed of 402 amino acid residues with a molecular mass of 46,163 Da. The derived amino acid sequence of the enzyme showed no significant sequence similarity to any other proteins reported so far. The 5-oxoprolinase gene was expressed in Escherichia coli by using a regulatory expression system with an isopropyl-beta-D-thiogalactopyranoside-inducible tac promoter, and its expression level was approximately 16 mg per liter. The purified enzyme has the same characteristics as the authentic enzyme, except for the amino terminus, which has three additional amino acids. The enzyme was markedly inhibited by p-chloromercuribenzoic acid, EDTA, o-phenanthroline, HgCl(2), and CuSO(4). The EDTA-inactivated enzyme was completely restored by the addition of Zn(2+) or Co(2+). In addition, the enzyme was found to contain 1 g-atom of zinc per mol of protein. These results suggest that the 5-oxoprolinase produced by A. faecalis N-38A is a zinc metalloenzyme.

Isoproterenol-induced myocardial injury resulting in altered S100A4 and S100A11 protein expression in the rat.

S-100 proteins (S100) are characterized by calcium-binding ability with two structural EF hands. Several S100 are expressed in cardiomyocytes and thought to play a crucial role in calcium signaling. To examine whether the expression of S100 is a response to detectable myocardial damage or regeneration, we investigated, immunohistochemically, the expression of S100A4 and S100A11 in the isoproterenol (ISP)-treated rat heart. Definite expression of S100A4 and S100A11 was demonstrated in normal cardiomyocytes, and their staining patterns were enhanced in the ISP-treated rat heart, suggesting the possible involvement of S1-A4 and S100A11 in ISP-induced myocardial damage.

Activation of the TCL1 protein in B cell lymphomas.

The TCL1 gene, localized near the break point of chromosome 14q32.1 often involved in T cell leukemias, is also expressed in normal precursor T and B cells, and B cell lymphoma cell lines. We investigated the expression of the TCL1 protein in various types of B cell lymphomas according to the Revised European-American Classification of Lymphoid neoplasms. Paraffin-embedded tissue sections of lymphoma specimens were subjected to TCL1 immunohistochemistry, and positivity was scored on a three-tiered scale: - (< 25% cells), + (25-50% cells), and ++ (> 50% cells). The TCL1 protein was expressed in low-grade B cell lymphomas including mucosa-associated lymphoid tissue type in ocular adnexa (18/20, 90%). It was also expressed in follicular, lymphoplasmacytic, and mantle cell lymphoma, but not in high-grade diffuse large B cell lymphoma (2/11, 18%). These data suggest that the expression of the TCL1 gene characterizes low-grade B cell lymphomas, and may be involved in certain processes of lymphomatogenesis.

Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells.

S100A4 is considered functionally involved in metastasis and invasiveness of rodent and human mammary tumors. We screened the expression of S100A4 in human squamous cell carcinoma cell lines, and found 2 cell lines which were highly invasive, but did not express any noticeable extent of S100A4. To examine whether the expression of S100A4 regulated invasiveness of squamous cell carcinoma, we transfected S100A4 cDNA into KOCS-3 and HSC-4 squamous cell carcinoma cells. The transfectants from KOSC-3 cells expressing sense S100A4 decreased invasiveness by 80% compared with cells of the wild type or those with the vector only.

Histological changes of the pancreas in an elderly diabetic patient positive for GAD antibody.

We examined the histological changes of the pancreas in a 75-year-old diabetic woman who was treated with sulphonylurea for 10 years and required insulin treatment for the subsequant 10 years. She was positive for antiglutamic acid decarboxylase antibody (GAD Ab) 20 years after the diagnosis of diabetes. Her autopsied pancreas revealed disfigured islets and no beta cells. These changes were indistinguishable from those of the long-sustained type 1 diabetes mellitus, and insulitis was not found. This case suggests that diabetic patients positive for the GAD Ab, even if oral hypoglycemic agents are effective, may develop complete beta cell destruction over a long period.