Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma.

Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues and hepatocellular carcinomas were determined for comparison with normal liver tissues. In hepatocellular carcinoma, glutamine synthetase activity was approximately one-third of that in normal liver, whereas no detectable change in the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and phosphate-independent glutaminase activities were increased approximately 20-fold and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with those from normal liver, Oxypolarographic tests showed that the rate of glutamine oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher than that in the liver mitochondria. The rate of glutamate oxidation in the liver mitochondria was comparable to that in the cirrhotic liver and tumor mitochondria. Glutamine oxidation was inhibited by prior incubation of the mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial glutaminase. These results indicate that the product of glutamine hydrolysis, glutamate, is catabolized in the tumor and cirrhotic liver mitochondria to supply ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via a transamination pathway in the tumor mitochondria.     

Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

Is preserving the entire aganglionic colon reasonable in the surgical treatment of total colonic aganglionosis?

Clinical reports describe an increased incidence of severe enterocolitis in infants with total colonic aganglionosis (TCA) following the Martin extended Duhamel procedure using the entire aganglionic colon. This study evaluates the efficacy of this procedure in an experimental model of TCA in comparison with an antimesenteric aganglionic colon patch in rats. TCA was produced by serosal application of 0.1% benzalkonium chloride in 18 Sprague-Dawley rats (250 g). Five additional rats served as operated controls. Ileoanal pull-through was performed in 18 TCA rats, in conjunction with the Martin extended Duhamel procedure using the entire colon in six rats, with an aganglionic colon patch in nine (using the right [3 rats], transverse [3 rats] and left [3 rats] colon), and without other procedures in three rats. Animals were evaluated for survival, weight change, food intake, stool consistency and volume, barium enema, complete blood cell count (CBC), total protein, and serum electrolytes at 4 and 12 weeks. Survival was 83% (5/6) rats with the Martin procedure, 100% in the nine rats with various colon patches, zero in three rats with ileoanal pull-through alone, and 100% in controls. Rats with the Martin procedure gained 2.2 +/- 3.27% of preoperative weight, while controls gained 11.2 +/- 0.52% at 4 weeks. All other rats showed an early weight loss. At 12 weeks, right and transverse colon patched rats had weight gain. Blood count and laboratory studies were similar in each group. Barium enema showed rapid transit in rats with ileoanal pull-through, and slower transit in rats with colon patches or the Martin procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent sleep attacks associated with a craniopharyngioma

Symptomatic narcolepsy, once regarded as common, is now believed to be very rare. A 32-year-old man had a history of recurrent sleep attacks. A magnetic resonance imaging scan revealed a third ventricle tumor. The tumor was totally removed, and the histology was a craniopharyngioma. The symptoms ceased after the operation. The chronological correlation and the anatomical location of the tumor suggest that the patient had a symptomatic narcolepsy caused by the tumor. This is the first report that documents the cessation of narcolepsy attacks after tumor removal.     

Clinical outcomes of two different endometrial preparation methods for cryopreserved-thawed embryo transfer in patients with a normal menstrual cycle

Aim:  To compare the clinical outcomes of cryopreserved-thawed embryo transfer among patients with a normal menstrual cycle who had natural or hormone-replacement cycles.
Methods:  From January 2004 to June 2006, cryopreserved embryos following conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were thawed and transferred in a total of 720 natural cycles and 136 hormone-replacement cycles.
Results:  Cryopreserved-thawed embryo transfer in patients who had a natural or hormone-replacement cycle resulted in clinical pregnancy in 43.1% and 40.4%, respectively; a rate of miscarriage of 14.5% and 23.6%, respectively; and a rate of ongoing pregnancy and delivery of 36.5% and 30.9%, respectively. None of these differences were statistically significant.
Conclusions:   Patients with a normal menstrual cycle who have natural or hormone-replacement cycles can be expected to have comparable clinical outcomes with cryopreserved-thawed embryo transfer. (Reprod Med Biol 2007; 6 : 53–57)     

Response of postapoplectic hemichorea/ballism to GPi pallidotomy: progressive improvement resulting in complete relief.

We report on a 66-year-old woman in whom GPi pallidotomy produced progressive and eventually complete relief of hemichorea/ballism (HCB) after a subthalamic hemorrhage. Although choreoballistic movements were unchanged during and immediately after the surgery, the symptoms were gradually improved and consequently abolished by 5 days postoperatively. HCB has never recurred up to the present (9 months follow-up period). This note is the first report describing detailed postsurgical process in HCB relief after pallidotomy.