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Lipomatous haemangiopericytoma (a fat-forming solitary fibrous tumour) is a rare soft-tissue tumour histologically characterized by haemangiopericytomatous vasculature and the presence of mature adipocytes. We report the CT and MRI findings of a case of lipomatous haemangiopericytoma involving the perineum. CT showed a well-circumscribed soft-tissue density mass containing a small area of fat density and a punctuate calcification. On MR images, the mass was mostly isointense to the muscle on T(1) weighted images, with heterogeneous signal intensity on T(2) weighted images, and showed strong contrast enhancement except for the fatty and dense collagenous components. This is the first case report of imaging findings of a lipomatous haemangiopericytoma in the radiological literature. Although rare, lipomatous haemangiopericytoma should be considered as a differential diagnosis of fat-containing, hypervascular soft-tissue tumours with variable signal intensity on T(2) weighted images.

The performance of Xpert(®) MTB/RIF assay, an automated nucleic acid amplification test (NAAT) that was developed for the detection of tuberculosis (TB), has been evaluated in various clinical settings. However, few studies have compared Xpert with other NAATs, especially its performance using lower respiratory tract specimens (LRTS).To compare the practical diagnostic performance of the Xpert assay with that of the AdvanSure™ TB/NTM RT-PCR kit in the detection of pulmonary TB (PTB), using LRTS obtained through bronchoscopy.Of 249 patients included, 105 had culture-confirmed PTB. Using culture as reference, the overall sensitivity of Xpert and AdvanSure was respectively 92.4% and 83.8%. When acid-fast bacilli smear results were taken into consideration, the sensitivity of Xpert for smear-positive and smear-negative LRTS was respectively 100% and 88.9%, while that of the AdvanSure was 100% and 76.4%. Xpert showed better results than AdvanSure in terms of sensitivity in smear-negative LRTS (P = 0.012), but no difference in smear-positive LRTS.Xpert may be advantageous in the detection of PTB using LRTS, particularly in low microbiological burden settings.

To evaluate the respondent burden and patient-perceived content validity of the Parkinson's disease (PD)-specific health status questionnaire PDQ-39, and the linguistic validity of its revised Swedish version.Eighteen PD patients completed the revised Swedish version of the PDQ-39. Respondent burden was assessed by recording the time taken to complete the questionnaire. Content and linguistic validity was evaluated qualitatively.Patients with mild, moderate and advanced PD needed a mean time of 9.5, 11.3 and 20.1 min, respectively, to complete the PDQ-39. One-third of the patients identified irrelevant items and 50% identified important health-related areas that were missing. Revisions had eliminated previous linguistic problems with the Swedish PDQ-39.Undue respondent burden challenged the appropriateness of the PDQ-39 among patients with more advanced disease. Overall content validity was acceptable but compromised by lack of important content areas. Observations supported the linguistic validity of the revised Swedish PDQ-39.

Although the internet may play a role in providing proper teratogen-risk counselling for pregnant women, the experience with this type of service has not been reported. We aimed to compare the pregnancy outcome of women counselled by the internet to women that received typically in-clinic teratogen risk counselling in the clinic. In a prospective cohort design, 1,011 patients were counselled in the clinic and 235 patients were counselled via the internet. Teratogen risk counselling was provided according with the information obtained from medical literature and specialised software. Information about pregnancy outcome (delivery, spontaneous abortion, or termination of pregnancy and major malformations) was obtained from 903 (89.3%) patients from the clinic group and 141 (60%) from the internet group. The amount of alcohol, cigarettes smoked, and millirads of X-ray were greater ( p < 0.05) in patients counselled by internet than in clinic. The rate of deliveries, ongoing pregnancies, pregnancy terminations, and spontaneous abortions were similar between clinic and internet (chi2 = 1.32; p = 0.7). Of 498 babies born to mothers counselled in the clinic, major malformations were identified in 3.6%. Of 67 babies born to mothers counselled by internet, major malformations were present in 1.5% ( p = 0.6). Teratogen-risk counselling by internet and clinic seems to have a similar efficacy in pregnancy outcome.

Several studies have reported an association between depression and folic acid deficiency. We investigated whether intake of prenatal multivitamins containing folic acid (MVandFA) was associated with decreased rates of depression among pregnant women. A questionnaire was given to 1,314 low-risk pregnant women. Of them, 1,277 (97.2%) women completed the questionnaire. The overall prevalence of depression was 8.1%. Of 652 participants who did not take MVandFA, 9.4% had depression, whereas 6.9% of 624 women who had MVandFA had depression (p = 0.11). In a multivariate logistic regression analysis, family history of depression (adjusted OR 3.7; 95% CI 1.9-7.3) and premenstrual syndrome (adjusted OR 3.0, 95% CI 1.8-4.8) were identified as risk factors for depression during pregnancy. In conclusion, intake of MVandFA was not associated with lower rates of depression during pregnancy whereas family history of depression and personal history of premenstrual syndrome were significant risk factors.

A 49-year-old white man with blood group AB, D+ was found to have alloanti-Jk(a) and -K when he developed a delayed hemolytic transfusion reaction before allogeneic hematopoietic stem cell transplant (HSCT). Given that his stem cell donor was blood group O, D+, Jk(a+), K-, rituximab was added to his conditioning regimen of fludarabine and melphalan to prevent hemolysis of engrafting Jk(a+) donor red blood cells. The patient proceeded to receive a peripheral blood stem cell transplant from a matched unrelated donor with no adverse events. To our knowledge, this is the first case of successful management of major non-ABO incompatibility caused by anti-Jk(a) in a patient receiving an allogeneic HSCT reported in the literature.

Little is known about exposures to low radiation doses in the first trimester of pregnancy and deterministic adverse effects in the offspring, and risks are extrapolated from catastrophic events or from exposures to radiotherapy. The study aimed to assess the foetal and neonatal outcomes of pregnant women exposed to radiodiagnostic procedures with abdominal or lumbar irradiation.In a prospective cohort design, we studied the foetal and neonatal outcomes in 115 singleton pregnant women who required abdominal or lumbar radiodiagnostic procedures without the administration of radionucleotides, and in 527 age-matched (± 2 years) control pregnant women.In the exposed group, lumbar spine radiography (33.9%), plain abdominal radiography (16.5%) and upper gastrointestinal tract radiography with abdominal irradiation (15.7%) were the most common radiodiagnostic procedures. Major congenital malformations were identified in two (1.9%) babies born in the exposed group and in two (0.4%) babies born in the control group (odds ratio = 4.7; 95% confidence interval 0.7-33.6; P = 0.15). The rest of the foetal and neonatal outcomes was similar in the two groups except by a marginally higher rate of admissions to the neonatal intensive care unit among babies born to exposed women (odds ratio = 2.9; 95% confidence interval 1.0-9.4; P = 0.06).Our results indicate that X-ray and computed tomography scan exposure involving abdominal irradiation without the administration of radionucleotides is not associated with adverse foetal and neonatal deterministic outcomes. Efforts are required to reduce the use of radiodiagnostic procedures for general check-ups in childbearing age women.

The utility of WBC cell population data (CPD) for the differential diagnosis of viral infection from normal control, bacterial infection, and tuberculosis in children was investigated.A data set of 602 total whole-blood samples were analyzed on the DxH 800 System for complete blood cell count (CBC) with leukocyte differential from children with the following sample breakdown: 77 confirmed diagnoses of viral infections (Epstein-Barr virus; 30, influenza A; 19, rota virus; 11, other viruses;17), 54 normal control, 71 bacterial infection, 17 TB patients, and 383 with various diseases. The mean (MN) and standard deviation (SD) of the volume (V), conductivity (C), five light-scatter measurements, and 14 calculated parameters were obtained for the leukocytes.Using a combination of the CBC and CPD parameter values, a decision rule, composed of 21 parameters, for the screening of viral infection in children was developed. Using this decision rule, 74 of 77 (96.1%) viral infections, two of 54 (3.7%) normal samples, one of 17 (5.9%) TB, and six of 71 (8.5%) bacterial infection samples were identified. The sensitivity was 96.1%, and specificity for normal control was 96.3% with an overall specificity of 93.7%. Fifty-nine samples of 383 samples (15.4%) collected from in-patient children with various diseases without confirmation of viral infection were included in this decision rule.In conclusion, the implementation of leukocytes CPD parameters can be useful in the detection of viral infection in children.

The present study was carried out to describe the epidemiologic characteristics of viral gastroenteritis and determine the phylogenetic composition of norovirus strains detected in hospitalized children with acute gastroenteritis in Seoul, Korea.In total, 10,603 stool samples were collected from 2004 to 2008 and tested by RT-PCR or ELISA. In 4,170 (39.3%) samples at least one viral pathogen was present. Rotavirus (RoV) (1,864, 17.5%) was found to be the causative agent followed by norovirus (NoV) (1,845, 17.4%), human adenovirus (HAdV) (266, 2.5%), human astrovirus (HAstV) (194, 1.8%), and sapovirus (SV) (1, 0.009%). Five GI genotypes (GI-1, GI-3, GI-4, GI-8, and GI-9) and eight GII genotypes (GII-2, GII-3, GII-4, GII-6, GII-7, GII-12, GII-16, and GII-17) of NoV were identified in acute gastroenteritis patients in 2008.The genetic characteristics of norovirus and the epidemiologic patterns of a viral pathogen from acute gastroenteritis patients may give potentially effective data for epidemiological studies in Seoul, Korea.

Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan.To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB).One hundred and ninety-nine patients were enrolled. Only procedures yieldingor =10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens15 mm were considered ineligible.The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.'s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0-2 vs. F3-4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005-1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213-0.949 respectively) with Marcellin et al.'s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131-0.685) with Chan's cutoffs.Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0-2) was the only factor to predict significant discordance between LB and LSM.

SUMMARYBetween January 2006 and May 2008, 2624 pregnant S. Korean women between 35–37 weeks gestation were screened for group B streptococcus (GBS). Resistance to antimicrobials was tested by disk diffusion and serotype determined using co-agglutination assays and microarray methods. Overall, 8% of pregnant women were colonized. Serotype III was the predominant serotype (43·8%), followed by serotypes V (20·3%), Ia (12·1%), and Ib (9·5%). GBS was frequently resistant to clindamycin (54·0%) and erythromycin (25·6%); 3·7% were resistant to cefazolin. More than three-quarters of serotype V were resistant to clindamycin or erythromycin or both, and 71% of serotype III were resistant to clindamycin but only 12% were resistant to erythromycin. GBS prevalence exceeded earlier reports by one-third. This is the first report of cefazolin resistance in Korea. These results underscore the need to establish screening measures and chemoprophylaxis guidelines regarding GBS infections in Korea.

Haemangioma is an extremely rare tumour of the ovary. We describe the CT and MRI findings of a heavily calcified ovarian haemangioma in a 69-year-old woman presenting with adnexal torsion. CT showed a well-circumscribed mass with extensive punctate calcifications, located posterior to the uterus. MR images showed dark signal intensities of the mass on both T(1) and T(2) weighted images, with poor enhancement of the mass on contrast-enhanced T(1) weighted images. MR images also demonstrated a beak-like protrusion from the adnexal mass, representing the adnexal torsion. This is the first case report of a heavily calcified ovarian haemangioma in the English literature. Although rare, ovarian haemangioma should be included in the differential diagnosis of a heavily calcified adnexal mass.

Although epidermal and dermal T cells play roles in the pathogenesis of fixed drug eruption (FDE), not much is known about keratinocyte death and its precise mechanism in FDE.Our aim is to elucidate the mechanism that underlies keratinocyte death in FDE, that is, the role of apoptosis and its signalling pathway.We first examined the involvement of apoptosis in the active FDE lesions by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) assay and immunohistochemical analysis of caspase-3. We then examined the expressions of Fas and Fas ligand (FasL) to deduce the possible upstream signalling pathway of apoptosis, if apoptosis were involved. We finally characterized the infiltrated T-cell subpopulations in the active FDE lesions.In the active FDE lesions, TUNEL positivity was strongly observed in the basal keratinocytes, and also weakly observed in the upper dermal infiltrates as well as in a few keratinocytes in the granular layer. The distribution of TUNEL-positive cells was similar to that of the strong staining of active capase-3. Fas was found mainly in the keratinocytes and some infiltrated dermal cells, whereas FasL was identified predominantly in the intraepidermal and dermal infiltrated cells and in some basal keratinocytes. Overlapping expression of Fas and FasL was accompanied by apoptosis in the FDE lesions. Many of the infiltrated mononuclear cells were CD8+. Perforin was rarely observed in the FDE lesions.These findings suggest that apoptosis of the keratinocyte is highly likely to be involved in the pathogenesis of FDE, and this cytotoxicity might be predominantly mediated by the FasL of the infiltrating CD8+ T cells, possibly also playing an inflammatory role.

There is some evidence of retroviral infection in ALS. A randomized, double-blind, placebo-controlled trial of indinavir in ALS was performed to assess safety and efficacy trends. Nephrolithiasis and gastrointestinal side effects were frequent with indinavir treatment. Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.

In this study we have identified a new structural motif for a ligand with G-quadruplex interaction that results in biological effects associated with G-quadruplex-interactive compounds. Fluoroquinolones have been reported to possess weak telomerase inhibitory activity in addition to their better known bacterial gyrase poisoning. Starting with a fluoroquinobenzoxazine, which has modest potency in a human topoisomerase II assay, we have designed a more potent inhibitor of telomerase that has lost its topoisomerase II poisoning activity. This fluoroquinophenoxazine (FQP) interacts with G-quadruplex structures to inhibit the progression of Taq polymerase in a G-quadruplex polymerase stop assay. In addition, we demonstrate by 1H NMR studies that this compound interacts with telomeric G-quadruplex structures by external stacking to the G-tetrad with both the unimolecular fold-over and the parallel G-quadruplex structures. A photocleavage assay confirms the FQP interaction site, which is located off center of the external tetrad but within the loop region. Molecular modeling using simulated annealing was performed on the FQP-parallel G-quadruplex complex to determine the optimum FQP orientation and key molecular interactions with the telomeric G-quadruplex structure. On the basis of the results of these studies, two additional FQP analogues were synthesized, which were designed to test the importance of these key interactions. These analogues were evaluated in the Taq polymerase stop assay for G-quadruplex interaction. The data from this study and the biological evaluation of these three FQPs, using cytotoxicity and a sea urchin embryo system, were in accord with the predicted more potent telomeric G-quadruplex interactions of the initial lead compound and one of the analogues. On the basis of these structural and biological studies, the design of more potent and selective telomeric G-quadruplex-interactive compounds can be envisaged.

Nine vitamin K3 analogs were compared with respect to the induction of the cytochrome P450 1A1 (CYP1A1) expression in mouse hepatoma Hepa-1c1c7 cells. 6-(4-Diethylamino)phenyl-7-chloro-5,8-quinolinedione (EA4) caused a significant induction of the CYP1A1-mediated ethoxyresorufin O-deethylase activity in a time- and concentration-dependent manner. The induction was accompanied by an increase of the Cyp1a1 mRNA transcription. The transient expression of the mouse Cyp1a1-CAT gene into cells showed that EA4 induced CAT activity. However, the aryl hydrocarbon receptor and its nuclear partner, aryl hydrocarbon receptor nuclear translocator mRNA transcription, were unaffected by the EA4 treatment. When the cells were incubated with EA4 in the presence of 1 nM TCDD, the ethoxyresorufin O-deethylase activity that was induced by TCDD was significantly suppressed by EA4. Inhibition of protein synthesis by cycloheximide strongly enhanced the EA4-dependent Cyp1a1 mRNA expression. Up-regulation of protein kinase C by a 2 h preincubation with phorbol 12-myristate 13-acetate increased the EA4-dependent expression of the Cyp1a1 gene. In human cells, such as HepG2 (human hepatocarcinoma), MCF-7 (human breast adenocarcinoma cell line), and HL-60 (human promyelocytic cell line), the expression of CYP1A1 mRNA was also induced by EA4 treatment. Moreover, CYP1B1 mRNA was increased by EA4 in MCF-7 cells. These results indicate that EA4 modulates CYP1A1 and CYP1B1 expressions by transcriptional activation. Also, protein kinase C may be involved in the induction mechanism of CYP1A1 by EA4.

To report experience with transverse sacral fracture, an uncommon injury frequently associated with neurologic deficit, and to perform a meta-analysis of the literature in order to define the role of decompression for the management of sacral fractures.A review of 7 cases.A university-affiliated tertiary care centre.Seven patients with transverse fractures of the sacrum. The mean follow-up was 13 months.A review of the clinical data and a search of the literature for studies that reported on 4 or more patients with a transverse sacral fracture.Mechanism of injury, type of neurologic deficit and its management.The most common mechanism in the 7 study patients was a fall from a height. Six patients had neurologic deficits, mostly in the form of bowel or bladder disturbance. Five of these were treated with surgical decompression, and 4 of them had an improvement in neurologic function. The 7 original studies from the literature dealt with a total of 55 patients. As in the study patients, falls from a height and motor vehicle accidents predominated as the mechanisms of injury. In contrast to patients in this study, 20 of 48 patients in the literature review with neurologic deficits were treated conservatively.The outcomes in this study are similar to those reported in the literature. The place of surgical decompression for patients with neurologic deficit cannot be clearly determined from the evidence currently available.

Recently we reported that resveratrol (trans-3,4',5-trihydroxystilbene) showed selective inhibition of recombinant human cytochrome P450 (P450) 1A1 in a concentration-dependent manner. The inhibition of recombinant human P450 1A1, 1A2, or 1B1 by various hydroxystilbene compounds having a similar structure to resveratrol was investigated using bacterial membranes from a human P450/NADPH-P450 reductase bicistronic expression system to find new candidates for cancer chemopreventive agents. Of seven compounds tested, rhapontigenin (3,3',5-trihydroxy-4'-methoxystilbene) exhibited a potent and selective inhibition of human P450 1A1 with an IC50 value of 0.4 microM. Rhapontigenin showed 400-fold selectivity for P450 1A1 over P450 1A2 and 23-fold selectivity for P450 1A1 over P450 1B1. Rhapontigenin did not show any significant inhibition of ethoxyresorufin O-deethylation (EROD) activity in human liver microsomes, the other human P450s such as P450 2E1, P450 3A4, P450 2D6, P450 2C8, and P450 2C9, or human NADPH-P450 reductase. We have further investigated the inhibition kinetics of P450 1A1 by rhapontigenin. Rhapontigenin inhibited EROD activity of expressed human P450 1A1 in a competitive manner. The loss of EROD activity was time- and concentration-dependent. The values for K(i) and k(inactivation) were 0.09 microM and 0.06 min(-1), respectively. The loss was not blocked by the trapping agents glutathione, N-acetylcysteine, or dithiothreitol. These results suggest that rhapontigenin is a potent mechanism-based inactivator of human P450 1A1 and may be considered as a good candidate for a cancer chemopreventive agent in humans.

The Virtual Tape Measure for the Operating Microscope (VTMOM) was created to assist surgeons in making accurate 3D measurements of anatomical structures seen in the surgical field under the operating microscope. The VTMOM employs augmented reality techniques by combining stereoscopic video images with stereoscopic computer graphics, and functions by relying on an operator's ability to align a 3D graphic pointer, which serves as the end-point of the virtual tape measure, with designated locations on the anatomical structure being measured. The VTMOM was evaluated for its baseline and application performances as well as its application efficacy.Baseline performance was determined by measuring the mean error (bias) and standard deviation of error (imprecision) in measurements of non-anatomical objects. Application performance was determined by comparing the error in measuring the dimensions of aneurysm models with and without the VTMOM. Application efficacy was determined by comparing the error in selecting the appropriate aneurysm clip size with and without the VTMOM.Baseline performance indicated a bias of 0.3 mm and an imprecision of 0.6 mm. Application bias was 3.8 mm and imprecision was 2.8 mm for aneurysm diameter. The VTMOM did not improve aneurysm clip size selection accuracy.The VTMOM is a potentially accurate tool for use under the operating microscope. However, its performance when measuring anatomical objects is highly dependent on complex visual features of the object surfaces.

A 1-mo toxicity study followed by a 1-mo recovery period of recombinant human basic fibroblast growth factor (bFGF) was performed using Beagle dogs at doses of 30, 120 or 480 mg/kg/d to estimate the no observed adverse effect level (NOAEL). Subcutaneous thickening was seen and its incidence, as well as that of stiffness of the injection sites, increased with dose. There were neither dead animals nor significant changes of body weight during the experimental period. In addition, no significant bFGF-related changes were found in ophthalmologic and histopathological examination, urinalysis and hematological, biochemical and organ weight parameters. At necropsy, red-brownish spots and/or nodule formations were recognized in a dose-dependent manner. Splenomegaly was noted in the 480 mg/kg group, but these findings had a low incidence in all dose groups. The findings in the dosing period disappeared or were ameliorated during the recovery period. The above data suggests the NOAEL of bFGF in Beagle dogs is480 mg/kg/d.

The short tandem repeats with repeat units ranging from two to several nucleotides became a powerful tool in the field of forensic identification and paternity determination as well as for research in human gene mapping. Allele and genotype frequencies for 9 short tandem repeats including HUMCSF1PO, HUMTH01, HUMPLA2A1, HUMF13A01, HUMCYAR04, HUMLIPOL, HUMHPRTB, HUMCD4, and HUMFABP were determined using PCR and subsequent analysis of the PCR products by denaturing polyacrylamide gel electrophoresis followed by silver-staining. DNA samples were obtained from about 100 Korean people and amplified in a thermocycler adopting glass capillaries rather than traditional tubes. We found that the bovine serum albumin was an essential additive for the capillary PCR, presumably to coat the inner surface of the capillary which may adsorb Taq DNA polymerase. The capillary thermocycler was very effective in reducing the cycling time such that most of the amplification reactions could be finished within 30 min albeit the PCR product was less than that for the tube systems. All loci except HUMHPRTB met the Hardy-Weinberg expectations according to the exact test. The cumulative power of discrimination (PD) was 0.9999998 and the power of exclusion (POE) for the paternity test was a little low, being 0.9873989.

To evaluate the findings of tetralogy of Fallot in various fetal sonographic views.We reviewed the fetal sonograms and medical records of 20 fetuses with prenatal diagnosis of tetralogy of Fallot. We analyzed the indications for targeted sonography, the abnormalities seen in various sonographic views, the postnatal echocardiographic and angiographic findings and autopsy findings.The most common indication for targeted sonography was an abnormal (n = 12) or inadequate (n = 3) finding on sonographic screening in which the abnormality was most frequently found on the three-vessel view (n = 9). The key pathological features of tetralogy of Fallot were uniformly demonstrated in the ventricular outflow tract, three-vessel and short-axis views. The ductus arteriosus was small in 70% of cases and not identifiable in the remaining fetuses. In three of six fetuses with no identifiable ductus, the ductus was shown to be absent at autopsy. The direction of ductal flow was variable.The key features of tetralogy of Fallot were always demonstrable in the ventricular outflow tract, three-vessel and short-axis views. The most common reason for referral was the abnormal three-vessel view.

We consider the analysis of correlated panel data in which two or more correlated multistate processes are periodically observed on each individual and the exact transition times between states are unknown. We describe a procedure that models each process marginally under a time-homogeneous Markov model allowing for covariates. The resulting estimators are shown to be asymptotically jointly normal with a covariance matrix that can be consistently estimated. Simultaneous inference procedures are also proposed. Methods are illustrated using data from an AIDS clinical trial to compare the toxic effects of two treatments on two hematologic variables, hemoglobin and absolute neutrophil count.

NK cells express several inhibitory receptors that recognize class I MHC molecules expressed on target cells. The NK cell inhibitory receptors (KIRs) provide a key regulatory function for NK cells via specific interaction with MHC/peptide complexes, but the molecular details for recognition of class I MHC molecules by KIRs still remain unclear. Here we report cDNA cloning and expression of p58 KIRs and a p50 killer cell activatory receptor (KAR) from a Korean blood donor and demonstrate direct binding between recombinant soluble p58 KIRs and recombinant soluble HLA-C molecules. We identified three p58/p50 killer cell receptors (KAR-K1, KIR-K6, and KIR-K7), which are homologous to p50 cl-39, p58 47.11, and p58 cl-6, respectively. Native gel shift assay revealed that p58 KIR-K6 and KIR-K7 bind both HLA-Cw3 and HLA-Cw6 molecules, but p50 KAR-K1 binds neither of the HLA-C molecules. However, binding of HLA-C molecule by p58 KIR is affected by the antigenic peptide bound on the MHC molecule, suggesting that the p58 KIR binding to the HLA-C molecule may be dependent on the peptide. In addition, the binding interaction requires the presence of both p58 Ig domains, suggesting that the binding mode of HLA-C and p58 KIR may have some similarity to that of the neonatal Fc receptor and the Fc fragment of Ab and may be distinct from that of TCR and MHC.

Yeast artificial chromosome (YAC) clones have been successfully utilized to generate a YAC contig map of the long arm of human chromosome 21 (Hu21q). The chromosome subband of 21q22.1 where five genetic loci (IFNAR1, IFNAR2, CRFB4, AF-1, and GART) are mapped is a gene-rich region and needs to be characterized in further detail. YAC D142H8 and YAC F136C5, which were characterized previously by a functional YAC expression procedure, and two new YAC clones, YAC 872B5 and YAC 876D4 located at 21q22.1 whose YAC sizes are 800 kb and 1,500 kb, respectively, were used in this study. To obtain more markers useful for making a detailed physical map of the region, a purified yeast artificial chromosome (YAC D142H8) was used to screen the 3 x 1 S cDNA library. As a result three anonymous cDNA clones (Kmy1, Kmy2, and Qorf4) were obtained, and the nucleotide sequences of Kmy1 and Kmy2 were determined. In an attempt to make a detailed physical map of the region, the locations of five known genes as well as the three new markers were determined on the four YACs by Southern blot analysis. YAC 872B5 contained all markers except GART while YAC F136C5, YAC D142H8, and YAC 876D4 contained three markers (CRFB4, IFNAR1, and IFNAR2), four markers (Kmy1, Kmy2, Qorf4 and AF-1), and four markers (Kmy1, Kmy2, Qorf4 and GART), respectively. YAC 872B5 may represent 1,500 kb of the 21q22.1 subband and half of the 3 x 1 S region, so it should be very useful for studying the relevent region of the human chromosome functionally and physically.

The allotype of human immunoglobulin kappa light chain constant region gene (IGKC) has been identified by the serological assay or DNA typing method. The three allotypes Km*1, Km*1,2 and Km*3 have amino acid substitutions at positions of codons 153 and 191 in the kappa light chain constant region. The Km allotypes were designated as follows: Km*1 has valine (GTC) at position 153 and leucine (CTC) at 191; Km*1,2 has Ala153 (GCC) and Leu191 (CTC); Km*3 has Ala153 (GCC) and Val191 (GTC). In this study, polymerase chain reaction-allele specific oligonucleotide (PCR-ASO) was used to provide a specific allelic typing system for the IGKC gene in 213 unrelated Koreans. For Km genotyping, the IGKC coding regions plus 35 bp of the 3' untranslated regions were amplified with specific primers. Amplified genes were hybridized with Km ASO probes at positions of codons 153 and 191 and were detected using a colorimetric detection method. The frequencies of Km*1,2/Km*1,2, Km*1,2/Km*3, and Km*3/Km*3 were 17.8% (n=38), 51.7% (n=110), and 30.5% (n=65), respectively. The estimated allele frequencies for Km*1,2 and Km*3 were 0.44 and 0.56, respectively. The homozygote or the heterozygote of Km*1 was not observed in this study. The PCR-ASO method distinguished the alleles Km*3, Km*1,2, and Km*1 and also distinguished the homozygote from heterozygote. Km frequencies vary significantly among various populations. Km*3 in Koreans was very similar to those observed in northern Chinese, Japanese, and the native people of British Columbia. It was lower than that reported in Caucasian, Indian, or southern Chinese.

The three-vessel view is a transverse view of the fetal upper mediastinum is as simple to obtain as the four-chamber view. It demonstrates the main pulmonary artery, ascending aorta and superior vena cava in cross- or oblique sections. The purposes of this study were to describe the normal anatomy of the three-vessel view and to analyze what anatomical changes would occur in this view when there are lesions of the ventricular outflow tracts and/or great arteries. Sonograms of 29 fetuses with lesions involving the ventricular outflow tracts and/or great arteries were reviewed. Three-vessel views were evaluated in terms of vessel size, number, arrangement and alignment. Twenty-eight of 29 fetuses showed an abnormal three-vessel view that included abnormal vessel size (n = 12), abnormal alignment (n = 8), abnormal arrangement (n = 7) and abnormal vessel number (n = 3). The vessel size was abnormal in obstructive lesions of the right (n = 4) or the left (n = 8) side of the heart. An abnormal alignment was seen in tetralogy of Fallot (n = 6) and double-outlet right ventricle (n = 2) that showed anterior displacement of the aorta. An abnormal arrangement was seen in complete (n = 4) and corrected (n = 1) transposition, double-outlet right ventricle (n = 1) and pulmonary atresia with ventricular septal defect (n = 1). Only two vessels were seen in truncus arteriosus (n = 1). Four vessels were seen in persistent left superior vena cava (n = 2). A fetus with pulmonary atresia and intact ventricular septum showed a normal three-vessel view. In conclusion, most of the lesions involving the ventricular outflow tracts and/or great arteries showed an abnormal three-vessel view.

This paper proposes a method for incorporating covariate information in the analysis of survival data when both the time of the originating event and the failure event can be right- or interval-censored. This method generalizes the one-sample estimation results of De Gruttola and Lagakos (1989, Biometrics 45, 1-11) by allowing the distribution of time between the two events to be a function of covariates under a proportional hazards model. Estimates for the model coefficients, as well as the underlying distributions, are obtained by an iterative fitting procedure based on Turnbull's (1976, Journal of the Royal Statistical Society, Series B 38, 290-295) self-consistency algorithm in combination with the Newton-Raphson algorithm. The method is illustrated with data from a study of hemophiliacs infected with the human immunodeficiency virus.

The biochemical signaling mechanisms involved in transducing the effects of tumor necrosis factor alpha (TNF alpha) and gamma-interferon (gamma-IFN) on leukemia cell differentiation are poorly defined. Recent studies established the existence of a sphingomyelin cycle that operates in response to the action of vitamin D3 on HL-60 cells and that may transduce the effects of vitamin D3 on cell differentiation (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). The effects of TNF alpha and gamma-IFN on sphingomyelin turnover were determined, and the specificity and role of sphingomyelin hydrolysis in HL-60 human promyelocytic leukemia cells with 20% hydrolysis of sphingomyelin at 15 min, 40% hydrolysis at 30-60 min, and return to base line at 2 h. The hydrolyzed sphingomyelin (18 pmol/nmol total phospholipid) was accompanied by the concomitant generation of ceramide (11.2 pmol/nmol total phospholipid). gamma-IFN also caused reversible hydrolysis of sphingomyelin with onset at 1 h and peak effect at 2 h. This sphingomyelin cycle appeared to be specific to the monocytic pathway of HL-60 differentiation, since it was not activated by retinoic acid or dibutyryl cAMP, inducers of granulocytic differentiation, nor with phorbol myristate acetate, an inducer of macrophage-like differentiation. Addition of synthetic ceramide or bacterial sphingomyelinase induced monocytic differentiation of HL-60 cells. Cell-permeable ceramide also caused prompt down-regulation of mRNA for the c-myc protooncogene. The time course of c-myc down-regulation was consistent with the action of ceramide as the mediator of TNF alpha action. These results suggest that sphingomyelin turnover may be an important signaling mechanism transducing the actions of TNF alpha and gamma-IFN with specific function in cell differentiation.