An unusual cause of small bowel obstruction: strangulated obturator hernia.
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Biomedical subjects
Publications and source records attributed to C Y Yu.
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This study elucidates the role of combined fluconazole and flucytosine as therapy for cryptococcosis in the murine model of meningitis. Three strains of Cryptococcus neoformans for which the range of fluconazole MICs was wide--2 microg/ml (susceptible strain), 8 microg/ml (moderately susceptible strain), and 32 microg/ml (resistant strain)--were used for infection. One day postinfection, the mice were randomized into eight treatment groups: placebo; flucytosine (40 mg/kg of body weight/day); fluconazole at 3 mg/kg/day (low dosage), 10 mg/kg/day (moderate dosage), or 20 mg/kg/day (high dosage); and combined flucytosine and fluconazole at low, moderate, or high doses of fluconazole. Three major findings were demonstrated: (i) correlation between the MICs for the isolates and the in vivo effectiveness of fluconazole as assessed by the reduction in cryptococcal brain burden, (ii) a dose-response curve (a higher dose of fluconazole was significantly more efficacious than a lower dose [P < 0.001]), and (iii) synergism between fluconazole and flucytosine (therapy with a combination of fluconazole and flucytosine was superior to therapy with either agent alone [P < 0.01]).
Potomac horse fever is an acute systemic equine disease caused by Ehrlichia risticii. Currently, serologic methods are widely used to diagnose this disease. However, serologic methods cannot determine whether the horse is presently infected or has been exposed to ehrlichial antigens in the past. The purpose of the present study was to compare the sensitivities of the nested PCR and cell culture with that of the indirect fluorescent-antibody (IFA) test for the diagnosis of Potomac horse fever. Blood and fecal specimens serially collected from a pony experimentally infected with E. risticii Maryland, blood specimens serially collected from mice inoculated with E. risticii Ohio 380, and blood and/or fecal specimens collected from 27 horses which had clinical signs compatible with Potomac horse fever were examined. These horses resided in Kentucky, Indiana, Pennsylvania, and Vermont. The IFA test titer became positive after 6 days postinoculation (p.i.) for the pony. A culture of the blood of the pony was positive for E. risticii starting on day 1 and was positive through day 28 p.i. By the nested PCR, E. risticii was detectable in the blood and feces of the pony starting on day 1 and was detectable through day 32 p.i. E. risticii was detected in the blood of subclinically infected mice by the nested PCR. Twenty-two clinical specimens were seropositive for E. risticii by the IFA test, with titers ranging from 1:20 to 1:1,280. E. risticii was cultured from 95% (20 of 21) of seropositive clinical blood specimens. E. risticii was detected in the blood by PCR in 81% (17 of 20) of the culture-positive clinical specimens. The study indicated that the nested PCR is as sensitive as culture for detecting infection with E. risticii.
Rc is a DNA binding protein with dual specificities for the V(D)J recombination signal sequences and for the B motif of the immunoglobulin kappa chain gene enhancer. The largest Rc transcript present in lymphoid cells/tissues is approximately 9 kb. Molecular cloning and sequence determination for 8822 bp of mouse Rc cDNA revealed an open reading frame of 2282 amino acids and long 5'- and 3'-untranslated regions. The derived amino acid sequence contains multiple DNA and protein interaction domains. Composite ZAS structures with tandem zinc fingers, an acidic motif, and a Ser/Thr-rich segment are located near the N-terminal and the C-terminal regions. The middle region of Rc contains a lone zinc finger, an acidic motif, a Ser-rich region, a nucleus localization signal, and GTPase motifs. Cloning and characterization of a mouse Rc gene show that the Rc cDNA corresponds to seven exons located in a genomic region spanning 70 kb. Exon 2 is exceptionally large, with 5487 bp. cDNA cloning and Northern blot analyses revealed multiple Rc transcripts, probably generated by alternative splicings. Sequence comparisons show that Rc belongs to a ZAS protein family that is involved in gene transcription and/or DNA recombination. The major histocompatibility complex class I gene enhancer binding proteins MBP1 and MBP2 are other representatives of this ZAS protein family.
Activity of the ubiquitously expressed Na+-H+ exchanger subtype NHE1 is stimulated upon activation of receptor tyrosine kinases and G protein-coupled receptors. The intracellular signaling pathways mediating receptor regulation of the exchanger, however, are poorly understood. Using transient expression of dominant interfering and constitutively active alleles in CCL39 fibroblasts, we determined that the GTPases Ha-Ras and Galpha 13 stimulate NHE1 through distinct signaling cascades. Exchange activity stimulated by constitutively active RasV12 occurs through a Rafl- and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase kinase (MEK)-dependent mechanism. Constitutively active Galpha 13QL, recently shown to stimulate the Jun kinase cascade, activates NHE1 through a Cdc42- and MEK kinase (MEKK1)-dependent mechanism that is independent of Rac1. Constitutively active Rac1V12 does stimulate NHE1 through a MEKK1-dependent mechanism, but dominant interfering Rac1N17 does not inhibit Galpha 13QL-mediated or constitutively active Cdc42V12-mediated stimulation of the exchanger. Conversely, Cdc42NI7 does not inhibit Rac1V12 activation of NHE1, suggesting that Rae I and Cdc42 independently regulate a MEKK1-dependent activation of the exchanger. Rapid (<10 min) stimulation of NHE1 with a Ga13/Gaz chimera also was inhibited by a kinase-inactive MEKK. Galpha 13QL, but not RasV12, also stimulates NHE1 through a RhoA-dependent pathway that is independent of MEKK, and microinjection of mutationally active Galpha 13 results in a Rho phenotype of increased stress fiber formation. These findings indicate a new target for Rho-like proteins: the regulation of H+ ex- change and intracellular pH. Our findings also suggest that a MEKK cascade diverges to regulate effectors other than transcription factors.
To overcome problems with conventional plastic endoprostheses, a study was conducted to determine the clinical efficacy of self-expandable metallic stents in the palliative treatment of malignant biliary obstruction. From May 1994 to March 1995, 19 self-expandable metallic stents were implanted in 13 consecutive patients with malignant obstructive jaundice due to cholangiocarcinoma (four patients), ampullary carcinoma (six), pancreatic carcinoma (one), and hepatic hilar lymph node metastasis (two). All patients underwent percutaneous transhepatic biliary drainage followed by stent insertion, except for two patients where the T-tube tract was used as access and another with previous placement of a polyethylene internal-external drainage catheter for more than 6 months. When both lobes of the biliary system were to be drained, stents were placed either side by side through punctured, separate hepatic ducts or, using a T configuration, through a single transhepatic tract. Percutaneous transhepatic stent placement was technically successful in all patients. After a mean follow-up of 5.9 months (range, 1-10 mo), 10 of 13 patients were still alive while three had died of nonprocedure-related causes. In 10 patients, total serum bilirubin levels decreased significantly (from 136.8 +/- 157 mumol/L to 34.2 +/- 22.2 mumol/L), while it increased in three patients. Two patients had stent occlusions at 2 and 3 months after stent placement, which required intervention. The overall patency period ranged from 1 to 9 months (mean, 5.1 mo). Our results confirm that the use of metallic stents is effective in the palliative treatment of malignant jaundice.
Helicases are essential enzymes for life because DNA replication, DNA repair, recombination, transcription, RNA splicing and translation all involve more than one helicase to unwind DNA or RNA. We have discovered, cloned and partially characterized a novel human helicase gene, SKI2W. The human SKI2W is located between the RD and RP1 genes in the class III region of the major histocompatibility complex (MHC) on chromosome 6, a genomic region associated with many malignant, genetic and autoimmune diseases. Derived amino acid sequence of human SKI2W showed an open reading frame for 1246 residues. It contains consensus sequences for structural motifs of an RNA helicase with a DEVH box. It has a leucine zipper motif that may be important for protein dimerization, and an RGD motif close to the N-terminus that might serve as a ligand for integrin or cell adhesion molecules. SKI2W shares a striking and extensive similarity to the yeast Ski2p that is involved in the inhibition of translation of poly(A) negative [poly(A)-] RNA, and plays an important role in antiviral activities. Human SKI2W fusion protein expressed in insect cells using a baculovirus vector has ATPase activity. The human SKI2W protein and the yeast Ski2p share extensive sequence similarities to another putative human protein KIAA0052, suggesting the presence of a new gene family that may be involved in translational regulation of cellular and viral RNA.
The complement component C4 genes of Old World primates exhibit a long/short dichotomous size variation, except that chimpanzee and gorilla only contain short C4 genes. In human it has been shown that the long C4 gene is attributed to the integration of an endogenous retrovirus, HERV-K(C4), into intron 9. This 6.36 kilobase retroviral element is absent in short C4 genes. Here it is shown that the homologous endogenous retrovirus, ERV-K(C4), is present precisely at the same position in the long C4 gene of orangutan and African green monkey. Determination of the short C4 gene intron 9 sequences from human, three apes, two Old World monkeys, and a New World monkey allowed the establishment of consistent phylogenetic trees for primates, which favors a chimpanzee-gorilla clade. The 5' long terminal repeats (LTR) and 3' LTR of ERV-K(C4) in long C4 genes of human, orangutan, and African green monkey have similar sequence divergence values of 9.1%-10.5%. These values are more than five-fold higher than the sequence divergence of the homologous intron 9 sequences between the long and short C4 genes in higher primates. The latter is probably a result of homogenization or concerted evolution. We suggest that the 5' LTR and 3' LTR of an endogenous retrovirus can serve as a reliable reference point or a molecular clock for studies of gene duplication and gene evolution. This is because the 5'/3' LTR sequences were identical at the time of retroviral integration and evolved independently of each other afterwards. Our data provides strong evidence for the short C4 gene being the ancestral form in primates, trans-species evolution, and the "slow-down" phenomenon of the sequence divergence in great apes.
Three Chinese girls with hypokalemic periodic paralysis secondary to different types of renal tubular acidosis are presented. One girl has primary distal renal tubular acidosis complicated with nephrocalcinosis. Another has primary Sjögren syndrome with distal renal tubular acidosis, which occurs rarely with hypokalemic periodic paralysis in children. The third has an isolated proximal renal tubular acidosis complicated with multiple organ abnormalities, unilateral carotid artery stenosis, respiratory failure, and consciousness disturbance. The diagnostic evaluation and emergent and prophylactic treatment for these three types of renal tubular acidosis are discussed.
Cytologic studies were done on fine needle aspirates of the lymph node and imprints of splenic biopsies from a patient with acute promyelocytic leukemia who was febrile while being treated with chemotherapy. Examination of the lymph node aspirates revealed pus and numerous pseudohyphae which were later identified as Candida tropicalis. When multiple nodular lesions were detected in the spleen by abdominal sonography and CT scan, needle biopsy of the spleen was done. Cytologic examination of touch imprints of the biopsy disclosed intracellular fungal blastospores. The patient was treated with and responded well to amphotericin B and 5-fluorocytosine. As a result of our experience with this patient we emphasize the importance of close incorporation of clinical information and diagnostic cytology. With such a cooperation, cytologic studies become a most useful method for diagnosis.
The influence of fat content on quantitative computed tomography (QCT) values was studied using porcine lumbar vertebrae as a model. A total of 72 cancellous bone columns, prepared from 18 vertebrae, underwent QCT examination before and after defatting. Mechanical testing and ashing were performed to obtain the ultimate strength and bone mineral content. The ultimate strength was calculated as a power function of apparent density using linear regression on a log-log plot and the power coefficient was 1.88. QCT values were positively correlated with bone density. QCT values of defatted specimens correlated much better with ultimate strength than those of fresh specimens. The average fat content was 27.2%. The QCT values decreased linearly with increasing fat content with a slope of 7.9 mg/cm3/% fat and a correlation coefficient of 0.65. The results provided basic data for the calibration of the machine and the principles for the interpretation of QCT values excluding the fat influence.
BACKGROUND: Biochemical changes inside the brain during acute ictus have been extensively studied by means of magnetic resonance spectroscopy (MRS). Previous reports revealed that cerebral cortical infarction causes reduction of N-acetylaspartate (NAA) and elevation of lactate. This study was designed to evaluate the biochemical changes in subcortical infarction. METHODS: Nine normal controls and four patients, including two thalamic infarct, one basal ganglia infarct, and one putamen infarct cases were examined using MRS in addition to magnetic resonance imaging (MRI). Evaluation experiments were performed on a Siemens Wagnetom 63SP machine. A spin echo sequence with TE 270 msec was applied for the measurement. The voxel was located at basal ganglia in the controls and at the lesion site, as well as at the contralateral corresponding region in the patients. RESULTS: Three resonance signals were present in the spectrum-NAA, choline-containing compounds (Cho) and creatine-phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios were reduced significantly on the lesion side compared with the controls. NAA/Cho also decreased on the lesion side compared with the healthy side. CONCLUSIONS: There is a remarkable reduction of NAA concentration even in subcortical infarction. Further study is needed for the detection of changes in lactate in patients with subcortical lesion.
Eleven cases of multicystic dysplastic kidney (MCDK) in children were diagnosed over an 11 year period. All underwent postnatal ultrasound (US) studies. Four different patterns of MCDK were recognized: (1) Six cases presented with the classic sonogram of multicystic components. (2) Three cases had hydronephrotic form; correct diagnosis between hydronephrotic form of MCDK and hydronephrosis was difficult as there was a medially-located, large, lobulated cyst and there was connection between the large cyst and neighboring small cysts. (3) One case initially presented with normal renal sonogram but a small cyst appeared on follow up sonogram and there was also decreased renal size and increased echogenecity. (4) One case had only two moderate-sized cysts but no identifiable renal parenchyma. Two cases had follow-up US examination and one dysplastic kidney decreased in renal size on follow-up sonogram. Intravenous urography and radionuclide study revealed both these dysplastic kidneys to be nonfunctioning. Nine children had surgical resection of the diseased kidneys. Contralateral renal anomalies were detected in five children, which included ureteropelvic junction stenosis, ureterovesical junction stenosis, distal ureteral stenosis and polycystic kidney disease. Two of three hydronephrotic forms of MCDK had contralateral ureteral stenosis. Two of six classic forms of MCDK had contralateral ureteral stenosis. The proportion of contralateral ureteral stenosis was higher in the group of hydronephrotic forms of MCDK. Ultrasonography is beneficial for conclusive diagnosis of MCDK; however, a differential diagnosis of simple hydronephrosis needs to be considered.
STUDY DESIGN AND OBJECTIVES: This study was conducted to depict the qualitative and quantitative changes of intervertebral rotation and translation from L1-L2 to L5-S1 during flexion, standing, and extension using dynamic lumbosacral radiographs. METHODS: A radiopaque ruler was placed on the back of each subject for the normalization of translational value. Eighty-nine volunteers were examined. RESULTS: From extension to flexion, all of the intervertebral rotations approached 0 degree from the lordotic position; the translations changed from slightly retro-listhetic to zero displacement. Using L3-L4 as a baseline for calculating the intervertebral differences in flexion, all of the rotational differences were less than 1.5 degrees, except at L5-S1, which remained 5 degrees. The mean translational difference was less than 0.6 mm, except at L5-S1, where it remained 1.5 mm. CONCLUSIONS: The amount of total flexibility was level-dependent and its frequency distribution is important. Qualitative rhythmic changes from extension to flexion and quantitative values of intervertebral difference in flexion help define the normal flexibility more accurately.
The correlation of many HLA-associated autoimmune and genetic diseases with the polymorphic complement C4 genes may be attributed to the presence of disease susceptibility genes in the close proximity of C4. We have cloned and characterized a pair of partially duplicated genes, RP1 and RP2, located 611 base pairs upstream of the human C4A and C4B genes, respectively. The putative RP protein, consisting of 364 amino acid residues, is basic and highly hydrophilic. There is a bipartite nuclear localization signal at residues 114-131 and therefore RP may be a nuclear protein. Northern blot analysis suggested that RP is ubiquitously expressed. The 5' region of the RP1 gene is CpG rich, which is a characteristic of housekeeping genes. The RP1 gene contains nine exons. Located in the fourth intron is a cluster of Alu elements, and a newly defined composite retroposon SVA with a SINE, multiple copies of GC-rich VNTRs and an Alu element altogether enclosed by direct terminal repeats. Members of SVA are also present in the complement C2 gene located about 20 kilobases upstream of RP1 in the HLA and in the cytochrome CYP1A1 gene. Determination of the DNA sequences for RP2 from two different HLA haplotypes revealed identical hybrid sequences which resulted from fusion of RP with the tenascin-like Gene X and truncation of the 5' regions of both genes. Cumulative data suggest that the four tandemly arranged genes RP, complement C4, steroid 21-hydroxylase (CYP21), and Gene X altogether form a modular structure, RCCX. The number of RCCX modules varies from one to three or more in the population. Absence of the truncated genes RP2 and Gene XA have been detected in genomes with single RCCX modules. Duplication of the RCCX modules probably occurred before the speciation of great apes and humans as they contain the same breakpoint region of RP and Gene X gene duplication.
The human complement C4 genes in the HLA exhibit an unusual, dichotomous size polymorphism and a four-gene, modular variation involving novel gene RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin-like Gene X (RCCX). The C4 gene size dichotomy is mediated by an endogenous retrovirus, HERV-K(C4). Nearly identical sequences for this retrotransposon are present precisely at the same location in the long C4 genes from the tandem RCCX Module I and Module II. Specific nucleotide substitutions between the long and short C4 genes have been identified and used for diagnosis. Southern blot analyses revealed that HERV-K(C4) is present at more than 30 locations in the human genome, exhibits variations in the population, and its analogs exist in the genomes of Old World primates with species-specific patterns. Evidence of intrachromosomal recombination between the two long terminal repeats of HERV-K(C4) is found near the huntingtin locus on chromosome 4. It is possible that members of HERV-K(C4) are involved in genetic instabilities including the RCCX modules, and in protecting the host genome from retroviral attack through an antisense strategy.
Pneumothorax, subcutaneous emphysema, and pneumomediastinum occur frequently in critically ill patients in association with blunt or penetrating injuries or other conditions while performing Valsalva-like maneuvers. We present the case of a patient with bilateral pneumothoraces, pneumomediastinum, pneumopericardium, and subcutaneous emphysema after acute paraquat intoxication.