The interleukin-1 genotype as a severity factor in adult periodontal disease

OBJECTIVE: To determine whether it is possible to predict the presence of bladder outlet obstruction (BOO) by non-invasive clinical variables in patients with lower urinary tract symptoms (LUTS) suggestive of BOO. PATIENTS AND METHODS: Patients with LUTS suggestive of BOO were entered into a prospective protocol evaluating the International Prostate Symptom Score (IPSS), prostate size, non-invasive uroflow, post-void residual urine volume (PVR) and a pressure flow study. Only patients with a maximum flow rate (Qmax) of < or = 15 mL/s and an IPSS > or = 7 were included. The study comprised 253 patients; the degree of obstruction was correlated to several non-invasive clinical variables. Subsequently nomograms were developed by multiple logistic regression analysis to obtain the probability of BOO in patients with LUTS. RESULTS: Prostate volume, Qmax, PVR and voided volume correlated significantly with the degree of BOO rated according to the linear passive urethral resistance relation (linPURR). In contrast, there was no such correlation for the IPSS and the quality-of-life question of the IPSS. The percentage of patients with BOO defined by a linPURR of 3-6 decreased from 85% in those with a Qmax of 0-5 mL/s to 60% (Qmax 6-10 mL/s) and 44% (Qmax 11-15 mL/s). In parallel, the percentage of patients with BOO increased from 53% of those with a prostate volume of < or = 50 mL, to 79% of those with prostates of 51-100 mL and 75% of those > 100 mL. Based on Qmax, PVR and prostate volume, nomograms were established by multiple logistic regression analysis for the probability of BOO in patients with LUTS. CONCLUSION: The nomograms presented herein should help the clinician to identify patients with LUTS who should undergo pressure flow studies before surgical intervention to detect the presence of obstruction and in whom these studies can be safely spared.     

Construction and characterization of a replication-deficient adenovirus expressing rat-soluble interleukin-6 receptor

BACKGROUND: The pleiotropic cytokine interleukin-6 mediates its multiple effects at the cell level through a multimeric receptor consisting of a binding protein (gp80) and a signal transducer (gp130). A soluble form of gp80 (sIL-6R or gp55) is found released from the surface of cells and appears to possess interleukin-6 (IL-6) agonist activity. Increases in circulating levels of sIL-6R have been reported in different pathological conditions but the precise role of this protein in vivo remains unknown. MATERIALS AND METHODS: The cDNA encoding the extracellular domain of the rat IL-6R (sIL-6R) with an appropriate leader sequence has been cloned into the E1 region of an adenovirus vector under the control of the hCMV promoter (Ad5.sIL-6R). RESULTS: Infection of different human or rodent cell lines with Ad5.sIL-6R leads to extended production of recombinant sIL-6R protein into the culture media. The kinetics of transgene expression depends both on the cell type and the species. sIL-6R produced in this manner is biologically active as it confers responsiveness of human hepatoma cells (HepG2) to rat IL-6 stimulation. Adenovirus vectors have been shown to be highly effective for transient delivery of cytokines in vivo. Antibodies against recombinant rat soluble IL-6R were generated and an ELISA developed that allowed us to quantify sIL-6R concentrations. The sIL-6R expressing adenovirus vector has been instilled intratracheally into rats and induced an increase in lung sIL-6R concentration from Day 1 up to Day 10. We demonstrate the potency of our system to deliver in vivo or in vitro soluble cytokine receptors in a prolonged but transient manner.     

Generating a normalized geometric liver model using warping

This review discusses the development and use of 5-hydroxytryptamine3 (5-HT3) antagonists, especially granisetron, for the treatment of chemotherapy-induced emesis. Following recent evidence suggesting that high-dose chemotherapy is more effective in increasing tumor response rate and median survival time, more effective antiemetic control is essential. Granisetron, a new 5-HT3, is approximately 400 times more potent than metoclopramide and, unlike metoclopramide, does not produce extrapyramidal side effects. Granisetron has been shown to be effective as a single prophylactic dose, over 5 days and in patients receiving repeated cycles of chemotherapy. Patients with nausea and vomiting within the first 24 h after chemotherapy are more likely to experience delayed symptoms; however, episodes of breakthrough nausea and vomiting can be controlled by intervention with one, and in some cases more, doses of granisetron. The development of granisetron represents an important advance in the control of chemotherapy induced emesis.     

The membrane topology of the amino-terminal domain of the red cell calcium pump

A systematic study of the membrane-associated regions in the plasma membrane Ca2+ pump of erythrocytes has been performed by hydrophobic photolabeling. Purified Ca2+ pump was labeled with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazirine ([125I]TID), a generic photoactivatable hydrophobic probe. These results were compared with the enzyme labeled with a strictly membrane-bound probe, [3H]bis-phosphatidylethanolamine (trifluoromethyl) phenyldiazirine. A significant light-dependent labeling of an M(r) 135,000-140,000 peptide, corresponding to the full Ca2+ pump, was observed with both probes. After proteolysis of the pump labeled with each probe and isolation of fragments by SDS-PAGE, a common pattern of labeled peptides was observed. Similarly, labeling of the Ca2+ pump with [125I]TID, either in isolated red blood cell membranes or after the enzyme was purified, yields a similar pattern of labeled peptides. Taken together, these results validate the use of either probe to study the lipid interface of the membrane-embedded region of this protein, and sustain the notion that the conformation of the pump is maintained throughout the procedures of solubilization, affinity purification, and reconstitution into proteoliposomes. In this work, we put special emphasis on a detailed analysis of the N-terminal domain of the Ca2+ pump. A labeled peptide of M(r) 40,000 belonging to this region was purified and further digested with V8 protease. The specific incorporation of [125I]TID to proteolytic fragments pertaining to the amino-terminal region indicates the existence of two transmembrane stretches in this domain. A theoretical analysis based on the amino acid sequence 1-322 predicts two segments with high probability of membrane insertion, in agreement with the experimental data. Each segment shows a periodicity pattern of hydrophobicity and variability compatible with alpha-helical structure. These results strongly suggest the existence of a transmembrane helical hairpin motif near the N-terminus of the Ca2+ pump.     

Puffer fish poisoning

Seven Vietnamese boat-people in Tai A Chau Detention Centre in Hong Kong caught, barbecued and ate a puffer fish. After 2 h, two of them developed severe symptoms of numbness and vomiting, while the remaining five subjects developed symptoms about 18 h later. They were all transferred to Queen Elizabeth Hospital. One patient died, and the others made an uneventful recovery.     

A study of hepatic mitochondrial respiration and microsomal cytochrome P450 content in mice infected with the liver fluke Fasciola hepatica

Previous studies of the effects of infection of Wistar rats with the common liver fluke, Fasciola hepatica, on liver bioenergetic and drug metabolism have demonstrated a loss of respiratory control in isolated mitochondria and reduced microsomal cytochrome P450 content, respectively, from 2 weeks post-infection throughout the acute phase of the infection. In the present study male Balb/c mice infected with F. hepatica showed a loss of respiratory control in isolated liver mitochondria only at 4 weeks post-infection. A similar time course was demonstrated for a reduction in hepatic microsomal cytochrome P450 content. Preparations from infected CBA mice showed similar changes to Balb/c mice but mitochondrial respiration in preparations from infected Swiss outbred mice was normal. A host difference between strains of mice and between mice and rats is therefore evident in the timing and extent of liver mitochondrial dysfunction and in the timing of the decrease in the cytochrome P450 content of hepatic microsomes. This difference between hosts may be related to the reported differences in cellular inflammatory responses to the migrating juvenile flukes in the livers of rats and mice.     

Longitudinal trends in total serum cholesterol levels in a Japanese cohort, 1958-1986

This study is a preliminary examination of the reliability of adolescent self-reported pretreatment alcohol and other drug (AOD) use frequency. Assessments of self-reported pretreatment AOD use were conducted at admission and discharge (approximately a 1-month time period) at an adolescent drug misuser treatment program. The sample consisted of 197 male and female adolescents. There were statistically significant increases between admission and discharge assessments of pretreatment AOD use frequency. The greatest discrepancy was found for alcohol use, in which three-fourths (76%) of the sample reported a higher level of pretreatment alcohol use frequency at discharge assessment as compared to their admission assessment. Over one-third (35%) of the sample was found to have a significantly higher level of pretreatment alcohol use frequency at discharge assessment. The cause of this response discrepancy is unknown, but if it represents underreporting at admission, it may cause diagnostic and referral errors, as well as attenuate effect sizes in treatment outcome studies.     

Protamine sulfate enhances lipid-mediated gene transfer

OBJECTIVE: To analyze myoelectric activity of the cecum and proximal loop of the ascending colon (PLAC) in cows after spontaneous cecal dilatation/dislocation (CDD) and compare it with that in healthy cows after surgical evacuation of the cecum. ANIMALS: 12 cows with spontaneous CDD and 6 healthy cows (group C). Cows with spontaneous CDD were retrospectively assigned to 2 groups: delayed recovery from surgery or recurrence (group A; n = 3), and normal recovery (group B; n = 9). PROCEDURE: After surgical evacuation of the cecum, 8 pairs of bipolar, retrievable electrodes were implanted in the ileum, cecum, and PLAC. Cows were evaluated daily from postoperative day 1 to 7, using routine clinical methods and computer-based analysis of myoelectric activity of the cecum, and PLAC. Parameters of myoelectric activity included rate of spike bursts, duration of individual spike bursts, duration of overall spike burst activity per electrode, rate of propagated spike burst sequences, and ratio of orally propagated spike burst sequences. RESULTS: Rate of spike bursts, duration of cecocolic spike burst activity, and ratio of orally to aborally propagated spike burst sequences did not vary among groups during the 7-day recording period. However, cows with delayed recovery had a typical, uniform pattern of myoelectric activity of the cecum and PLAC at days 1 and 2 after surgery that consisted of repeated, propagated spike burst sequences, made up of spike bursts of significantly (P < 0.05) increased duration at postsurgical day 1 and substantially prolonged duration at postsurgical day 2, interrupted by periods of little or no activity. CONCLUSION: Delayed recovery and recurrence of CDD in cows after spontaneous CDD is not caused by hypomotility of the cecum and PLAC. CLINICAL RELEVANCE: Postoperative treatment, intended to reduce recurrence of CDD or delayed recovery after surgical evacuation of the cecum, should address propagation of digesta in the spiral colon.     

Cardioprotection by orotic acid: metabolism and mechanism of action

The pyrimidine base, orotic acid (OA), improves the function of recently infarcted hearts subjected to global ischemia but its mechanism of action is unclear. Our aims were to examine (i) in normal rats, the effect of OA on pyrimidine levels in plasma, liver and heart; (ii) in rats with normal or infarcted hearts, the effect of OA on adenine nucleotide metabolism and mechanical function, before and after global ischemia. To investigate the metabolism of OA, normal rats received 100 mg/kg OA, and changes in plasma and tissue concentrations of pyrimidines were examined. The effects of OA were also studied in rats receiving OA for 2 days after coronary ligation or sham operations, and plasma and tissue pyrimidine concentrations examined. Their hearts were isolated and perfused, then subjected to 30 min of global ischemia. Mechanical function and adenine nucleotide content were assessed pre- and post-ischemia. In normal, unoperated rats, administration of 100 mg/kg OA significantly increased hepatic uracil and cytosine nucleotide concentrations, then increased plasma uridine (+124%) and cytidine (+55%), and transiently increased myocardial uracil nucleotides (+21%). Infarction significantly reduced recovery of cardiac work after global ischemia (sham=62%; infarct=26%; P<0.05), and OA treatment in infarcted hearts increased post-ischemic work by 192% (P<0.05), but not in shams. Pre-ischemic ATP was reduced in the surviving myocardium of infarcted hearts from 21.7+/-0.8 to 14.7+/-0. 7 micromol/g dry weight (P<0.001) and total adenine nucleotides (TAN) from 30.3+/-0.8 to 22.4+/-1.1 micromol/g dry weight (P<0.001). OA treatment prevented these reductions in infarcted hearts (ATP 20. 7+/-0.5; TAN, 29.1+/-0.6 micromol/g dry weight). We conclude that OA protects the infarcted heart against global ischemia by enhancing hepatic release of pyrimidine nucleosides into the plasma, which then prevent depletion of adenine nucleotides in the surviving myocardium.     

The Himar1 mariner transposase cloned in a recombinant adenovirus vector is functional in mammalian cells

Mariner transposons belong to the mariner /Tc1 superfamily of class II, DNA-mediated elements. One of these transposons, Himar1 , isolated from the horn fly, is independent of host-specific factors that would limit transfer between different species, making it an ideal candidate for gene transfer technology development. To determine the activity of Himar1 transposase in mammalian cells, we introduced the Himar1 transposase gene into an adenovirus (Ad) vector under control of the phage T7 RNA polymerase promoter. Mammalian cells infected with the Ad vector carrying the Himar1 gene efficiently expressed the Himar1 transposase in the presence of T7 polymerase. In in vitro inter-plasmid transposition reactions, Himar1 transposase expressed by the Ad vector mediated precise cut-and-paste transposition and resulted in a characteristic duplication of TA at the integration site of the target plasmid. Further studies showed that this transposase was capable of catalyzing transposition between twoplasmids co-transfected into 293T7pol cells, which express T7 RNA polymerase. Combining the integration capability of mariner transposons with the transduction efficiency of Ad vectors is expected to provide a powerful tool for introducing transgenes into the host chromosome.