Transjugular intrahepatic portosystemic shunt placement in a patient with absent right superior vena cava and persistent left superior vena cava.
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Biomedical subjects
Publications and source records attributed to J Miller.
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In four experiments, increasing the intensities of both relevant and irrelevant auditory stimuli was found to increase response force (RF) in simple, go/no-go, and choice reaction time (RT) tasks. These results raise problems for models that localize the effects of auditory intensity on purely perceptual processes, indicating instead that intensity also affects motor output processes under many circumstances. In Experiment 1, simple RT, go/no-go, and choice RT tasks were compared, using the same stimuli for all tasks. Auditory stimulus intensity affected both RT and RF, and these effects were not modulated by task. In Experiments 2-4, an irrelevant auditory accessory stimulus accompanied a relevant visual stimulus, and the go/no-go and choice tasks were used. The intensity of the irrelevant auditory accessory stimulus was found to affect RT and RF, although the sizes of these effects depended somewhat on the temporal predictability of the accessory stimulus.
Previous findings suggest that motoric response preparation cannot be initiated in parallel with memory scanning. In the present study, response preparation was initiated with the aid of a precue to examine whether such preparation can be maintained or continued while memory scanning is active. In Experiment 1, each trial began with a colored square indicating which hand might be needed to respond. A probe letter's memory set membership determined whether the primed response should be made or withheld. Lateralized readiness potentials were initiated by the square precue and continued to increase after letter presentation, suggesting that once response preparation had been initiated it was continued in parallel with memory scanning. Experiment 2 suggested that the difficulty of the concurrent memory search had little effect on the continuation of response preparation. The results support the view that motoric response preparation consists of at least two qualitatively distinct phases--initiation and continuation.
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The repair of large and/or recurrent ventral hernias is associated with significant complications and a recurrence rate that can be more than 50 per cent. Laparoscopic ventral herniorrhaphy, a recent development, has been shown to be safe and effective in the repair of ventral hernias. This study retrospectively reviews all ventral hernia repairs over a 3-year period, November 1995 through December 1998, at a community-based teaching hospital. The purpose of the study was to compare open and laparoscopic repairs. A total of 253 ventral hernia repairs were performed during this time, 174 open and 79 laparoscopic. The age, weight, and sex distribution was similar for each group. The hernias in the open group averaged 34.1 cm2 in size, and mesh used averaged 47.3 cm2. In the laparoscopic group, the hernia defect averaged 73.0 cm2, and the mesh size averaged 287.4 cm2. Operative time was longer in the open group, 82.0 versus 58.0 minutes. In the open group, there were 38 (21.8%) minor and 8 (4.6%) major complications, compared with 13 (16.5%) minor and 2 (2.5%) major complications in the laparoscopic group. Hospital stay was shorter for the laparoscopic group, 1.7 versus 2.8 days. At an average follow-up of 21 months (range, 2-40 months), there have been 36 recurrences in the open group (20.7%) compared with 2 recurrences in the laparoscopic group (2.5%). In this series, laparoscopic ventral herniorrhaphy compares favorably to open ventral herniorrhaphy with respect to wound complications, hospital stay, operative time, and recurrence rate.
Of the 1,679 renal allografts performed at the University of Miami between January 1, 1979 and October 31, 1999, 1,154 were from cadaver donors (CAD), 515 were from living-related donors (LRD), and 10 were from living-unrelated donors. The 3 ethnic groups: Black Caribbean-African-American, Hispanic, and others were almost equally represented among recipients. Recipient ages ranged between 1-83 years. In the CAD group, HLA matching was emphasized so that no patient received a kidney with less than one DR match, and for the entire series a mean of 2.59 of 6 HLA antigens were matched between donors and recipients. Overall actuarial 20-year patient and graft survival rates were 65.3% and 30.7%, respectively, with 69.2% patient and 38.5% graft survival rates for LRD, and 65.6% patient and 29.0% graft survival rates for CAD recipients. Several factors adversely affected long-term graft outcome. African-Americans had an overall 20-year graft survival rate of 13.6% compared with 34% for non African-Americans (p < 0.001) (not dependent on patient survival). Diabetic patients had an overall 20-year graft survival rate of 13.5% versus 34.2% for non-diabetics (primarily dependent on patient survival). In the category of non African-American, non-diabetic patients under age 36 (n = 412), the 20-year patient survival rates in the LRD and CAD groups were 85.0% and 79.3%, respectively, and the graft survival rates were 55.7% and 46.5%, respectively. This differed markedly from the results for the entire series.
OBJECTIVE: To assess the effect on natural extrinsic dental stain by use of a dentifrice containing 1% tetrasodium polyphosphate (TSPP), 7% sodium tripolyphosphate (STPP), 0.243% sodium fluoride and 10% high cleaning silica (HCS) over an eight-week period was compared to a sodium fluoride/silica placebo dentifrice without stain removal ingredients. METHODS: Ninety one subjects were selected and stratified into two balanced groups randomly assigned to use the test dentifrice or the placebo dentifrice. The two groups were well balanced with regard to their mean baseline stain index scores, gender and tobacco habits. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice and a commercially available soft bristled toothbrush. Extrinsic dental stain examinations, which included mean stain area and mean stain intensity, were conducted at baseline, four and eight weeks. The same dental examiner conducted examinations on the subjects at each examination. RESULTS: After eight-week use of their assigned products, those subjects in the TSPP/STPP/HCS dentifrice group demonstrated a statistically significant (P = 0.0001) stain reduction of 37.1%, as compared to the fluoride placebo dentifrice group without stain removal ingredients. CONCLUSION: The use of a dentifrice containing 1% tetrasodium polyphosphate, 7% sodium tripolyphosphate, 0.243% sodium fluoride and 10% high cleaning silica is effective in reducing natural extrinsic dental stain, when compared to a placebo fluoride dentifrice.
Radiation target analysis has been used to identify the minimal functional unit for expression of activity of ClpP, the proteolytic component of the ATP-dependent ClpAP protease. Radiation target sizes determined for small peptide hydrolysis, for ClpA activated and nucleotide-activated oligopeptide cleavage, and for ClpA-activated ATP-dependent protein degradation were 154, 118, and 160 kDa, respectively. Thus, the hydrolytic activity of ClpP, subunit M, 21,500, is dependent on the native oligomeric structure. The quaternary structure of ClpP determined by electron microscopy and hydrodynamic studies consists of two face-to-face seven-membered rings. The radiation target sizes are consistent with a requirement for conformational integrity of an entire ring for expression of hydrolytic activity. Radiation damage led to disruption of inter-ring contacts, giving rise to isolated rings of ClpP. Thus, contacts between rings of ClpP are less stable and more easily disrupted than contacts between subunits within the rings. Our data suggest that cooperative interactions between subunits within the ClpP rings are important for maintaining the active conformation of the proteolytic active site.
BACKGROUND: Hepatitis C infection recurs after orthotopic liver transplantation for hepatitis C virus (HCV)-related end-stage liver disease. Overlapping histopathologic features may present difficulties in differentiating recurrent HCV in the allograft from other conditions, especially rejection. METHODS: In this study, we evaluated the presence of HCV-RNA by reverse transcriptase in situ polymerase chain reaction (RT in situ RCR) in hepatic tissue, after orthotopic liver transplantation for HCV-related liver disease. Further, detection of HCV-RNA was correlated with the serum HCV-RNA levels, histopathology, and clinical outcome. RESULTS: Twenty-five patients were part of this study. Seventeen patients were transplanted for HCV cirrhosis and eight for an underlying disease other than HCV. None of the patients in the non-HCV group had in situ RT-PCR detection of HCV-RNA. Positive RT in situ PCR for HCV was found in 9 of 17 HCV patients, and the patients had a clinical course consistent with recurrent hepatitis C disease. Four of these nine patients had an initial histologic diagnosis of rejection. The other eight patients in the HCV group had negative RT in situ PCR, and none of them had a course compatible with recurrent HCV disease, although four patients were histologically diagnosed as having chronic C hepatitis. The mean HCV-RNA level (log/mL) in the patients who had in situ detection of HCV-RNA was 7.01+/-0.26. Although RT-PCR was negative in 8 of 17 HCV patients, the patients were serologically viremic and the mean HCV-RNA level was 6.05+/-0.33 (P=0.03). CONCLUSIONS: Our findings indicate that the HCV in situ RT-PCR assay may be helpful in the differentiation of recurrent hepatitis C disease from rejection. This may further help in the adjustment of immunosuppression.
We describe the first potent and selective blocker of the class E Ca2+channel. SNX-482, a novel 41 amino acid peptide present in the venom of the African tarantula, Hysterocrates gigas, was identified through its ability to inhibit human class E Ca2+ channels stably expressed in a mammalian cell line. An IC50 of 15-30 nM was obtained for block of the class E Ca2+ channel, using either patch clamp electrophysiology or K+-evoked Ca2+ flux. At low nanomolar concentrations, SNX-482 also blocked a native resistant or R-type Ca2+ current in rat neurohypophyseal nerve terminals, but concentrations of 200-500 nM had no effect on R-type Ca2+ currents in several types of rat central neurons. The peptide has the sequence GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH and is homologous to the spider peptides grammatoxin S1A and hanatoxin, both peptides with very different ion channel blocking selectivities. No effect of SNX-482 was observed on the following ion channel activities: Na+ or K+ currents in several cultured cell types (up to 500 nM); K+ current through cloned potassium channels Kv1.1 and Kv1. 4 expressed in Xenopus oocytes (up to 140 nM); Ca2+ flux through L- and T-type Ca2+ channels in an anterior pituitary cell line (GH3, up to 500 nM); and Ba2+ current through class A Ca2+ channels expressed in Xenopus oocytes (up to 280 nM). A weak effect was noted on Ca2+ current through cloned and stably expressed class B Ca2+ channels (IC50 > 500 nM). The unique selectivity of SNX-482 suggests its usefulness in studying the diversity, function, and pharmacology of class E and/or R-type Ca2+ channels.
The alpha-toxin of Clostridium perfringens is the major virulence determinant for gas gangrene in man. The gene encoding the alpha-toxin has been cloned into E. coli from two strains of the bacterium (NCTC8237 and CER89L43) and subsequently purified to homogeneity. The two strains of alpha-toxin differ by five amino acids, resulting in the toxin from NCTC8237 being sensitive to chymotrypsin digestion while that from CER89L43 is resistant. The alpha-toxin from each of these strains has been crystallized in two different forms by the hanging-drop vapour-diffusion method at 293 K. CER89L43 form I crystals belong to space group R32 and have two molecules in the crystallographic asymmetric unit and a unit cell with a = b = 151.4, c = 195.5 A, alpha = beta = 90, gamma = 120 degrees. The crystals diffracted to dmin = 1.90 A. The characteristics of the NCTC8237 form I crystals have already been reported. The form II crystals from both strains belong to space group C2221 with one molecule in the crystallographic asymmetric unit and, for strain CER89L43, have cell dimensions a = 61.05, b = 177.50, c = 79.05 A, alpha = beta = gamma = 90 degrees, while for strain NCTC8237 the cell dimensions are a = 60.50, b = 175.70, c = 80.20 A, alpha = beta = gamma = 90 degrees. The crystals diffracted to maximum resolutions of 1.85 and 2.1 A for the CER89L43 and the NCTC8237 strains, respectively.
Retinoic acid (RA) and dibutyryl cAMP plus theophilline (CT) trigger F9 cells to differentiate into parietal endoderm. The differentiation induces a 9-fold increase in total heparan sulfate (HStotal) biosynthesis and a 170-fold increase in anticoagulantly active HS (HSact) biosynthesis. Measurement of 3-O-sulfotransferase-1 mRNA and enzymatic activity demonstrated an increase of over 100-fold whereas determination of N-, 2-O, and 6-O-sulfotransferase enzymatic activities showed elevations of 2-, 3. 5-, and 3.7-fold, respectively. HSact precursor pool measurements reveal that 30% of control F9 HStotal can be converted into HSact while only an additional 10% of RACT F9 HStotal can be transformed into HSact. Disaccharide analysis of metabolic labeled HS indicated that 32% 3-O-sulfate containing disaccharides, i.e. GlcA-anManR3S and GlcA-anManR3S6S, are present in HSact and 68% GlcA-anManR3S and GlcA-anManR3S6S are found in anticoagulantly inactive HS (HSinact). By using adenosine 3'-phosphate 5'-phosphosulfate and purified 3-O-sulfotransferase-1, 30% of 3-O-sulfation occurs in HSact and 70% of 3-O-sulfation occurs in HSinact. The similar ratio of 3-O-sulfate distribution in HSact versus HSinact suggests that HSact production in the F9 system is determined by the abundance of 3-O-sulfotransferase-1 as well as the size of the HSact precursor pool. Extensively 3-O-sulfated HSinact may play an important functional role under in vivo conditions within the murine placenta.
A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.
Thirteen neuropeptide Y (NPY) agonists were administered intracerebroventricularly (i.c.v.) in rats (full dose-response curves) to estimate their half-effective dose (ED50) on feeding. These values were compared to their binding affinities (IC50) for rat NPY receptor subtypes Y1, Y2, Y4 and Y5 in vitro. Correlations between in vivo ED50 and in vitro IC50 were strong for the Y5 (r = 0.87; P < 0.01), weak for the Y1 (r = 0.48; P < 0.04) and non-significant for the Y2 and Y4 receptor subtypes. In vitro, h[D-Trp32]NPY was found to be a Y5-selective ligand and a full agonist in Y5-expressing cells. In vivo, it dose-dependently stimulated feeding, but failed to induce the full maximal response observed with pNPY. It did not antagonize pNPY-induced feeding and overfeeding in 24 h fasted rats. These findings demonstrate a role for the Y5, or possibly Y5 in combination with Y1, but not Y2 or Y4 receptor subtypes in feeding. No evidence was found for the existence of an additional, as yet undescribed, NPY feeding receptor.
The major site of interaction between MHC class II molecules and invariant chain has been mapped to occupancy of the class II peptide-binding site by the CLIP region of invariant chain. CLIP is also seen as a degradation product of invariant chain and can be found in association with class II as a processing intermediate. Here we analyzed the relative contribution of single amino acids in the murine CLIP (86-102) peptide for binding to I-Ab and I-Ad and for recognition by a CLIP-specific T cell hybridoma. Interestingly, the I-Ab-restricted murine T cell hybridoma that recognizes murine CLIP peptide (86-102) is dependent on Met 102 for activation. This amino acid is outside of the core binding region and in the CLIP/DR3 crystal structure extends outside of the class II peptide-binding site. These data suggest that a T cell epitope presented on CLIP/class II complexes can be located predominantly in flanking residues that extend out of the peptide binding groove of class II.
Transgenic mutation assays utilizing bacterial target genes display a high frequency of spontaneous mutation at CpG sequences. This is believed to result from the fact that: (1) the prokaryotic genes currently being used as transgenic mutation targets have a high CpG content and (2) these sequences are methylated by mammalian cells to produce 5-methylcytosine (5MC), a known promutagenic base. To study the effect of CpG content on the frequency and type of spontaneous mutation, we have synthesized an analogue of the bacterial lacI target gene (mrkII) that contains a reduced number of CpG sequences. This gene was inserted into a lambda vector and used to construct transgenic mice that undergo vector rescue from genomic DNA upon in vitro packaging. Results on spontaneous mutation frequency and spectrum have been collected and compared to those observed at the lacI gene in Big Blue transgenic mice. Spontaneous mutations at the mrkII gene occurred at a frequency in the mid-10-5 range and were predominantly base pair substitutions, similar to results seen in Big Blue. However, mrkII mutations were distributed toward the carboxyl end of the gene instead of the bias toward the amino terminus seen in lacI. Unexpectedly, 23% of the spontaneous mrkII mutations were GC-->AT transitions at CpG sequences (compared to 32% in lacI), despite the reduction in CpG number from 95 in lacI to only 13 in mrkII. Nine of the CpG bases undergoing transition mutations in mrkII have not been recorded previously as spontaneous sites in Big Blue. Therefore, substantial reduction of the number of CpG sequences in the lacI transgene did not significantly reduce the rate of spontaneous mutation or alter the contribution of CpG-related events. This suggests that other factors are also operating to establish frequency and composition of spontaneous mutations in transgenic targets.
BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.