The factor-for-inversion stimulation protein (Fis) is a global regulatory protein in Escherichia coli that activates ribosomal RNA (rRNA) transcription by binding to three upstream activation sites of the rRNA promoter and enhances transcription 5- to 10-fold in vivo. Fis overexpression results in different effects on cell growth depending on nutrient conditions. Differential proteome analysis of Fis-expressing cells shows ten protein spots corresponding to Fis overexpression in both rich (YT) and minimal (M9+glucose) media. Three of these spots have been identified as elongation factor TS, histidine-binding periplasmic protein precursor, and ketol-acid reductoisomerase.

Bacterial Proteins↗

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The relationship of conjoint traits of dyslipidemias between young offspring and their parents in a community-based sample.

BACKGROUND: The relationship of dyslipidemias between young offspring and their parents was examined to evaluate its usefulness in predicting lipid disorders among parents and children. METHODS: Young offspring ages 5-17 years and their parents were studied in a community-based sample of 477 families. The dyslipidemias were defined as: (1) isolated high low-density lipoprotein cholesterol (LDL-C); (2) isolated high triglycerides (TG) and/or low high-density lipoprotein cholesterol (HDL-C); and (3) combined, involving both above. RESULTS: Children of parents with a given dyslipidemia type had the highest frequency of the same disorder (P < 0.001 to P < 0.05). In discriminant analyses only the corresponding disorders in their parents were selected into the models as significant predictors after controlling parental obesity. In terms of sensitivity, 54.8, 50.0, 66.7, and 69.1% of offspring could be correctly predicted for isolated TG/HDL-C, isolated LDL-C, combined, and any type of disorder, respectively, by the corresponding disorders in both parents. Likewise, the predictability of parent's dyslipidemia from their children's disorder was also modest. CONCLUSION: The conjoint dyslipidemias have familial basis to provide rationale for parents or children to determine their own risk status; however, sensitivity and positive predictive values are not high enough to be useful as a selective screening tool.

Adolescent↗

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Role of protein kinase C in mediating alpha-1-adrenoceptor-induced negative inotropic response in rat ventricles.

The aim of this study was to determine the effect of protein kinase C (PKC) activation on intracellular Ca(2+) transient and its relation to alpha(1)-adrenoceptor (alpha(1)-AR)-stimulated negative inotropic response in rat ventricles. The electromechanical responses to phenylephrine (PE) in rat ventricular muscles were concomitantly examined using the conventional microelectrode method. The responses of intracellular Ca(2+) transient and cell contractions to PE in the absence of certain pharmacological interventions were ascertained in fura-2-loaded myocytes. The influence of PE on L-type Ca(2+) current (I(Ca,L)) was also examined using a voltage clamp in a whole-cell configuration. PE did not alter the action potential parameters during the negative inotropic phase. The negative inotropic effect (NIE) was inhibited by prazosin, chloroethylclonidine (CEC) and staurosporine, but was insensitive to pertussis toxin. Desensitization of PKC after prolonged pretreatment of rat ventricles with PDBu also abolished the NIE of PE. Caffeine modulated the NIE, but thapsigargin did not. The evoked intracellular Ca(2+) transient and cell contraction were initially decreased by PE, while I(Ca,L) was not altered. Prazosin and staurosporine significantly inhibited the responses. Our data indicated that alpha(1)AR-mediated NIE in rat ventricular muscles was due to the decrease of intracellular Ca(2+) transients by the modulation of PKC on Ca(2+)-releasing channels signaling through a CEC-sensitive alpha(1)AR subtype.

Adrenergic alpha-1 Receptor Antagonists↗

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Modulatory effects of the human heat shock protein 70 on DNA vaccination.

DNA vaccination with the plasmid expressing Japanese encephalitis virus (JEV) nonstructural protein 1 (pJNS1) has been shown to induce effective immunity against JEV infection. To further increase the efficacy of pJNS1 DNA vaccination, we coinjected pJNS1 with a plasmid that expresses heat shock protein 70.1 (pHSP70.1) into mice. We found that coinjection of pHSP70.1 enhanced both T cell proliferation and cytotoxic effects, but not the antibody response to JEV. Moreover, mice immunized with both pHSP70.1 and pJNS1 were resistant to lethal challenges of JEV, indicating that the protective immunity against JEV is not decreased, in spite of the low antibody titer via the immunization of pHSP70.1. Since DNA vaccination administered by pJNS1 did not elicit strong cellular immunity in our previous study, the administration of pHSP70.1 apparently could be used as an adjuvant to enhance cell-mediated immunity in this model system. Thus, coadministration of pHSP70.1 DNA with plasmid DNA encoding tumor- or virus-specific antigens might be very useful in the treatment of cancers and other infectious diseases.

Adjuvants, Immunologic↗

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Neurotoxic effect of acamprosate, n-acetyl-homotaurine, in cultured neurons.

Acamprosate (AC), N-acetyl-homotaurine, has recently been introduced for treating alcohol craving and reducing relapses in weaned alcoholics. AC may exert its action through the taurine system rather than the glutamatergic or GABAergic system. This conclusion is based on the observations that AC strongly inhibits the binding of taurine to taurine receptors while it has little effect on the binding of glutamate to glutamate receptors or muscimol to GABA(A) receptors. In addition, AC was found to be neurotoxic, at least in neuronal cultures, triggering neuronal damage at 1 mM. The underlying mechanism of AC-induced neuronal injury appears to be due to its action in increasing the intracellular calcium level, [Ca2+](i). Both AC-induced neurotoxicity and elevation of [Ca2+](i) can be prevented by taurine suggesting that AC may exert its effect through its antagonistic interaction with taurine receptors.

Acamprosate↗

PubMedDate not supplied

S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effect against N-methyl-D-aspartate receptor-mediated neurotoxicity.

Glutamatergic neurotransmission, particularly of the NMDA receptor type, has been implicated in the excitotoxic response to several external and internal stimuli. In the present investigation, we report that S-methyl-N,N-diethylthiocarbamate sulfoxide (DETC-MeSO) selectively and specifically blocks the NMDA receptor subtype of the glutamate receptors, and attenuates glutamate-induced neurotoxicity in rat-cultured primary neurons. Other major ionotropic glutamate receptor subtypes, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate, were insensitive to DETC-MeSO both in vitro and in vivo. Disulfiram, the parent compound of DETC-MeSO, also inhibits glutamate receptors partially in vivo; however, it fails to inhibit glutamate receptors in mice pretreated with N-butyl imidazole, a cytochrome P450 enzyme inhibitor, implicating the need for bioactivation of disulfiram to be an effective antagonist. We showed that glutamate-induced increase in (45)Ca2+ was attenuated in rat-cultured primary neurons following pretreatment with DETC-MeSO. The Ca2+ influx into primary neurons, studied by confocal microscopy of the fluorescent Ca2+ dye fura-2, demonstrated a complete attenuation of NMDA-induced Ca2+ influx. Similarly, DETC-MeSO attenuated NMDA-induced (45)Ca2+ uptake. Glutamate-induced (45)Ca2+ uptake and Ca2+ influx, however, were partially blocked by DETC-MeSO, and this is consistent with both in vitro and in vivo studies in which DETC-MeSO partially blocked mouse brain glutamate receptors. In addition, DETC-MeSO pretreatment effectively prevented seizures in mice induced either by NMDA, ammonium acetate, or ethanol-induced kindling seizures, all of which are believed to be mediated by NMDA receptors. These data demonstrate that DETC-MeSO produces the neuroprotective effect through antagonism of NMDA receptors in vivo.

Alcohol Withdrawal Seizures↗

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Cavernous transformation of the portal vein secondary to tumor thrombosis of hepatocellular carcinoma: spiral CT visualization of the collateral vessels.

BACKGROUND: We investigated the constituting collateral vessels in cavernous transformation of the portal vein (CTPV) caused by tumor thrombosis of hepatocellular carcinoma (HCC) by using contrast-enhanced spiral computed tomographic (CT) examination. METHODS: Fifty-four histopathologically proven HCC patients with tumor thrombosis-induced CTPV were retrospectively included and assigned to cirrhosis negative (n = 31) and positive (n = 23) groups. Another 15 cirrhotic patients with portal hypertension but no HCC and CTPV were used for comparison. Standardized dual-phase contrast-enhanced spiral CT was performed for all patients. CT appearances of the collateral vessels of CTPV were observed, and their visualization rates were analyzed. RESULTS: Biliary (cystic and paracholedochal veins) and gastric (left and right gastric veins) branches of the portal vein were the most frequently visualized collateral vessels of CTPV. There was a marked difference in CT visualization rates for biliary branches between patients with and without CTPV (83-94% vs. 0). No difference existed in visualization rates for gastric branches across the three groups (77-87% for left gastric, 58-61% for right gastric vein). CONCLUSIONS: Biliary and gastric branches of the portal vein are the major collateral vessels of CTPV. The intergroup differences in CT visualization rates may provide clues to the roles that they might play in the hemodynamic adaptation process of CTPV.

Adult↗

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Percutaneous implantation of a Port-Catheter System using the left subclavian artery.

PURPOSE: To evaluate the safety and feasibility of a percutaneous Port-Catheter System (PCS) implanted via the subclavian artery (SCA) for regional chemotherapy or chemoembolization of thoracic, abdominal, and pelvic malignant tumors. METHODS: Percutaneous puncture of the SCA was performed in 256 patients with thoracic, abdominal, or pelvic malignant tumors; then a catheter was inserted into the target artery. After the first transcatheter chemotherapy or chemoembolization with an emulsion of lipiodol and anticancer agents, an indwelling catheter was introduced with its tip placed in the target artery and its end subcutaneously connected to a port. RESULTS: The procedure was successfully completed in all 256 cases (100%). The indwelling catheter tip was satisfactorily placed in the target arteries in 242 cases (98%). Complications attributable to the procedure occurred in 20 (7.8%) cases, including pneumothorax (n = 10, 4%), hemothorax (n = 1, 0.4%), infections in the pocket (n = 4, 1.6%), and hematoma at the puncture site (n = 5, 2%). There were no severe sequelae or deaths. The duration of PCS usage was 1-36 months (median 9.5 months). During the course of treatment, occlusion of the target artery occurred in 20 cases (7.8%). Dislocation of the tip of the indwelling catheter occurred in 12 cases (4.7%); in 10 of the 12, the tip of the indwelling catheter was repositioned into the target artery. In all 10 cases no large symptomatic hematomas developed after the PCS was removed. CONCLUSION: Percutaneous PCS implantation via the left SCA, a relatively new procedure, is a safe and less invasive treatment approach than surgical placement for malignancies.

Abdominal Neoplasms↗

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Role of pleural fluid C-reactive protein concentration in discriminating uncomplicated parapneumonic pleural effusions from complicated parapneumonic effusion and empyema.

The aim of this study was to determine whether pleural fluid C-reactive protein (CRP) is useful in distinguishing complicated parapneumonic pleural effusion (CPPE) and empyema from uncomplicated parapneumonic pleural effusions (UPPE). A total of 69 consecutive patients with parapneumonic effusions were enrolled in the study: 29 with UPPE, 29 with CPPE, and 11 with empyema. Concentrations of standard biochemical parameters together with CRP in the pleural fluid were measured using an immunoturbidimetric assay. Pleural CRP was significantly higher in CPPE (11.6 mg/dl) and in empyema (12.2 mg/dl) than in UPPE (3.9 mg/dl). A cutoff value of 8.7 mg/dl for pleural CRP in the diagnosis of CPPE and empyema resulted in a sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) of 0.80, 0.97 and 0.94, respectively. Traditional lactic dehydrogenase (LDH) > or = 1000 U/L and glucose < or = 60 mg/dl can differentiate CPPE and empyema from UPPE, with the sensitivity, specificity, and AUC achieving 0.75/0.60.1.00/1.00,0.95/0.22, respectively. However, for the detection of CPPE and empyema, the combination of pleural fluid CRP > or = 8.7 mg/dl and LDH > or = 1000 U/L was valuable in achieving a sensitivity, specificity, and AUC of 0.97/1,00/0.95. This study suggests that measurement of pleural CRP can be useful in the workup of patients with a parapneumonic effusion in order to differentiate CPPE from UPPE.

Adult↗

PubMedDate not supplied

Mast cells in the bovine lower respiratory tract: morphology, density and distribution.

The lower respiratory tract of six 8-day-old calves and six adult cows was fixed in either isotonic formal-acetic-acid or neutral buffered formalin in order to study the morphology, density and distribution of mast cells. They were found at all levels of the tract with the highest density in the major bronchi. Tissues from cows had significantly more mast cells than those from calves. There were significantly more mast cells detected in calf airways fixed with isotonic formal-acetic-acid compared with those seen in the same tissues fixed with neutral buffered formalin. Regardless of the age and fixation, mast cells were located predominantly in the alveolar septa and in the lamina propria of airways. They were also commonly encountered within the mucosal epithelium of the trachea. Ultrastructurally, mast cells in bovine airways and lung contained two types of intracytoplasmic granules as described in other species.

Animals↗

PubMedDate not supplied

The inhibition of bovine heart hexokinase by 2-deoxy-D-glucose-6-phosphate: characterization by 31P NMR and metabolic implications.

The glucose analog, 2-deoxy-D-glucose (2DG), has been used widely for studying the initial steps in the metabolism of glucose by radio-isotope tracer methods and by 31P NMR. In the rat heart perfused with acetate/2DG (both 5 mM) plus insulin, trapping of phosphorus by 2-deoxy-D-glucose-6-phosphate (2DG6P) results in a steady state exhibiting high 2DG6P (55 mM) and low ATP concentrations but near-normal function, as observed in an earlier 31P NMR study. In order to understand how the 2DG6P concentration is stabilized, we studied the inhibition of a mammalian hexokinase by 2DG6P in vitro by a 31P NMR technique. Inhibition, previously unobserved, was found. It is similar to inhibition by G6P in that it is competitive with ATP and not competitive with 2DG, but the inhibition constant (1.4 mM) is much larger. The experimental protocol includes provisions for enzymatic destruction of stray inhibitors such as G6P. The results show that the high 2DG6P and low ATP concentrations found in the steady state of the perfused heart should strongly reduce the rate of phosphorylation of sugars by hexokinase.

Animals↗