Rate of glutamate synthesis from leucine in rat brain measured in vivo by 15N NMR

The rate of glutamate synthesis from leucine by the branched-chain aminotransferase was measured in rat brain in vivo at steady state. The rats were fed exclusively by intravenous infusion of a nutrient solution containing [15N]leucine. The rate of glutamate synthesis from leucine, determined from the rate of increase of brain [15N]glutamate measured by 15N NMR and the 15N enrichments of brain and blood leucine analyzed by gas chromatography-mass spectrometry, was 0.7-1.8 micromol/g/h at a steady-state brain leucine concentration of 0.25 micromol/g. A comparison of the observed fractional 15N enrichments of brain leucine (0.42 +/- 0.03) and glutamate (0.21 +/- 0.015) showed that leucine provides approximately 50% of glutamate nitrogen under our experimental condition. From the observed rate (0.7-1.8 micromol/g) and the known Km of the branched-chain aminotransferase for leucine (1.2 mM), the rate of glutamate synthesis from leucine at physiological brain leucine concentration (0.11 micromol/g) was estimated to be 0.35-0.9 micromol/g/h, with leucine providing approximately 25% of glutamate nitrogen. The results strongly suggest that plasma leucine from dietary source, transported into the brain, is an important external source of nitrogen for replenishment of brain glutamate in vivo. Implications of the results for treatment of maple-syrup urine disease patients with leucine-restricted diet are discussed.     

Stage I rectal cancer: identification of high-risk patients

BACKGROUND: Stage I rectal cancer (T1, T2 N0) is currently treated by surgical resection alone. Despite adequate surgical resection, approximately 10-15% of patients will develop recurrence. Identification of patients at high risk for recurrence could potentially lead to an improvement in outcome by selection of these patients for adjuvant therapy. METHODS: Between June 1986 and September 1996, 211 patients with primary rectal cancer (stage I) were treated by radical surgical resection alone. The medical data of all patients were entered into a database and prospectively followed. The following 10 prognostic factors were correlated with recurrence and tumor-related mortality: patient factors: age, gender, and preoperative carcinoembryonic antigen level; tumor factors: location from the anal verge (< 6 cm vs. > or = 6 cm), T stage (T1 vs. T2), intratumoral blood vessel invasion (BVI), intratumoral lymphatic vessel invasion, presence of tumor ulceration, and histologic differentiation; and treatment-related factors: extent of surgical resection--abdominal perineal resection versus low anterior resection. Univariate analysis of the effect of the prognostic factors on recurrence and tumor-related mortality were performed by the method of Kaplan-Meier and log rank test. Independent prognostic factors were determined by a multivariate analysis performed using the Cox proportional hazards model. RESULTS: The overall 5-year actuarial recurrence was 12% and tumor-related mortality was 10%. Independent predictors of recurrence were male gender and BVI. Independent predictors of tumor-related mortality were male gender, BVI, and poorly differentiated tumors. CONCLUSIONS: Despite radical resection, patients with stage I rectal cancer with male gender, BVI, and poorly differentiated tumors should be considered high-risk patients.     

Triplex targets in the human rhodopsin gene

We have explored the application of triplex technology to the human rhodopsin gene, which encodes a G-protein-linked receptor involved in the genetic disorder autosomal dominant retinitis pigmentosa (ADRP). Our results support the hypothesis that most human genes contain high-affinity triplex sites and further refine the rules governing identification and successful targeting of triplex-forming oligonucleotides (TFOs) to these sites. Using a computer search for sites 15 nucleotides in length and greater than 80% purine, we found 143 distinct sites in the rhodopsin gene and comparable numbers of sites in several other human genes. By applying more stringent criteria, we selected 17 potential target sites in the rhodopsin gene, screened them with a plasmid binding assay, and found 8 that bound TFOs with submicromolar affinity (Kd = 10(-)9-10(-)7 M). We compared purine (GA) and mixed (GT) TFOs at each site, and found that GA-TFOs consistently bound with higher affinity, and were less sensitive to pyrimidine interruptions in the target strand. High G-content favored high-affinity binding; only sites with >54% G-content bound TFOs with Kd 相似文献   

Recovery of Pd from Spent Fuel: 3. Recovery of Pd from Nitric Acid Solutions Using Carbamoyl Phosphine Oxides

Extraction and sorption recovery of Pd from nitric acid solutions with extractants containing carbamoyl phosphine oxides (CMPO) was studied. The Pd distribution coefficients under different extraction conditions were determined. The possibility of Pd recovery in the course of spent nuclear fuel processing was demonstrated. A number of solid extractants composed of carbamoyl phosphine oxides and inert matrices (styrene-divinylbenzene polymer and silica gel) were tested. The Pd distribution coefficients in the course of sorption and desorption under the static and dynamic conditions were measured.__________Translated from Radiokhimiya, Vol. 47, No. 4, 2005, pp. 343–346.Original Russian Text Copyright © 2005 by Zaitsev, Kvasnitskii, Korolev, Babain, Pokhitonov.     

FGF-18, a novel member of the fibroblast growth factor family, stimulates hepatic and intestinal proliferation

The fibroblast growth factors (FGFs) play key roles in controlling tissue growth, morphogenesis, and repair in animals. We have cloned a novel member of the FGF family, designated FGF-18, that is expressed primarily in the lungs and kidneys and at lower levels in the heart, testes, spleen, skeletal muscle, and brain. Sequence comparison indicates that FGF-18 is highly conserved between humans and mice and is most homologous to FGF-8 among the FGF family members. FGF-18 has a typical signal sequence and was glycosylated and secreted when it was transfected into 293-EBNA cells. Recombinant murine FGF-18 protein (rMuFGF-18) stimulated proliferation in the fibroblast cell line NIH 3T3 in vitro in a heparan sulfate-dependent manner. To examine its biological activity in vivo, rMuFGF-18 was injected into normal mice and ectopically overexpressed in transgenic mice by using a liver-specific promoter. Injection of rMuFGF-18 induced proliferation in a wide variety of tissues, including tissues of both epithelial and mesenchymal origin. The two tissues which appeared to be the primary targets of FGF-18 were the liver and small intestine, both of which exhibited histologic evidence of proliferation and showed significant gains in organ weight following 7 (sometimes 3) days of FGF-18 treatment. Transgenic mice that overexpressed FGF-18 in the liver also exhibited an increase in liver weight and hepatocellular proliferation. These results suggest that FGF-18 is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine.     

Pulmonary vasodilation by ketamine is mediated in part by L-type calcium channels

We studied the effects of ketamine in the isolated rat lung under conditions of increased pulmonary arterial pressure using the thromboxane A2 mimic, U46619, and in response to ventilatory hypoxia. Ketamine caused dose-dependent vasodilation, and possible mechanisms were evaluated using verapamil, meclofenamate, N(omega)-L-nitro-L-arginine benzyl ester (an inhibitor of nitric oxide synthase), and U-38883A (an ATP-sensitive potassium channel antagonist) in the isolated blood-perfused rat lung. Under increased tone conditions, N(omega)-L-nitro-L-arginine benzyl ester, meclofenamate, and U-38883A had no significant effect in attenuating ketamine-induced vasodilator responses. In a final series of experiments, verapamil significantly attenuated ketamine-induced vasodilator responses. These data suggest that ketamine has significant vasodilator activity in the pulmonary vascular bed of the rat, which seems to be mediated by an L-type calcium channel-sensitive pathway. These responses are not mediated or modulated by the release of nitric oxide, the activation of K+ ATP channels, or the release of vasodilator cyclooxygenase products. IMPLICATIONS: In this study, we examined the mechanism of the vasodilator effects of ketamine in the blood-perfused rat lung. The results of the present study suggest that ketamine-induced vasodilator responses are mediated by an L-type calcium channel-sensitive pathway.     

Frequently missed diagnosis in geriatric psychiatry

Older adults are an important segment of the population that has specific health care needs. Their unique biopsychosocial characteristics impact the presentation, evaluation, and management of psychiatric illnesses. This article describes how common psychiatric disorders present in an aging population. Research in this area is relatively new and much more information is still needed. Close attention should be paid to new knowledge as it emerges about this growing population.     

Speed, sex, gay men, and HIV: ecological and community perspectives

OBJECTIVE: To find a means of bladder augmentation that would avoid the complications encountered with the use of bowel segments, using a newly developed acellular biomaterial, the bladder acellular matrix graft (BAMG), as a homologous graft. MATERIALS AND METHODS: Thirty-four rats underwent a partial cystectomy (40-50%) and grafting with a BAMG of equal size. Eleven rats died within the first 72 h. probably from urinary leakage caused by obstruction of the bladder neck with stones or coagula; the surviving 23 were killed at varying intervals after cystectomy and examined. RESULTS: After providing initial bladder enlargement, the graft was progressively infiltrated by the vessels and smooth muscle cells of the host: furthermore, the mucosal lining was complete within 10 days. After 4 weeks, all bladder wall components were evident histologically in the graft. The ingrowth was complete after 8 weeks, except for neural regeneration, which was only partial. At 12 weeks, the bladder wall muscle structure in the graft was so well developed that it was difficult to delineate the junction between host bladder and BAMG. Neural regeneration continued to improve. Normal bladder capacities were maintained throughout the study. CONCLUSION: The BAMG appears to serve, without rejection, as a framework of collagen and elastin for the ingrowth of all bladder wall components. The reason for the better acceptance of the BAMG than of other bladder augmentation grafts requires further investigation.     

Improved results in the management of surgical candidates with lung cancer

BACKGROUND: Perioperative mortality and morbidity after lung resection for carcinoma are generally reported to be 3% to 6% and 15% to 30%, respectively, and higher in the elderly and those with limited cardiopulmonary reserve. METHODS: To minimize this risk and extend the surgical option to more high-risk patients, we adopted a protocol in 1991 that included preoperative digitalis, subcutaneous heparin and venoocclusive stockings, aggressive perioperative pulmonary toilet, and video-directed limited resections for many patients with limited pulmonary reserve. In October 1996, we reviewed our results with 173 consecutive patients (median age, 60 years; range, 17 to 89 years) undergoing operation for suspected lung carcinoma. Forty-one patients were 70 years old or older, and 70 patients were considered high risk on the basis of advanced age (> or = 70 years), poor cardiac or pulmonary reserve, or serious medical comorbidity. Procedures included pneumonectomy (n = 31), lobectomy (n = 83), bilobectomy (n = 12), and limited resection (n = 45). Two patients had unresectable disease. RESULTS: Hospital mortality was 1.6% (3/173) and morbidity was experienced by 15% (26/173). Among the high-risk subgroup mortality was 4.2% (3/70) and morbidity was 20% (14/70; p < 0.03). For the older patients these values were 4.8% (2/41) and 17.9% (7/41), respectively. CONCLUSIONS: Morbidity and mortality from lung resections may be minimized with the perioperative management strategy outlined above. This would allow more high-risk patients to benefit from surgical resection, and do so with an acceptably low risk.