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Biomedical subjects

C H Chang

Publications and source records attributed to C H Chang.

At least 217 records · Page 12Linked to original sources

ESX: a structurally unique Ets overexpressed early during human breast tumorigenesis.

The >30 known members of the Ets multigene family of transcriptional regulators are increasingly being recognized for their involvement in early embryonic development and late tissue maturation, directing stage-specific and tissue-restricted programs of target gene expression. Identifiable primarily by their 85 amino acid ETS DNA-binding domain and dispersed across all metazoan lineages into distinct subfamilies, Ets genes also produce malignancies in humans and other vertebrates when overexpressed or rearranged into chimeras retaining the ETS domain, suggesting that their oncogenic potential is determined by the program of target genes they regulate. Searching for Ets factors that regulate expression of the HER2/neu (c-erbB2) oncogene in human breast cancer, we identified a new epithelium-restricted Ets encoding an ETS domain homologous to the Drosophila E74/human Elf-1 subfamily, an amino-terminal region (A-region or Pointed domain) homologous to the distantly related Ets-1 subfamily, and a serine-rich box homologous to the transactivating domain of the lymphocyte-restricted High Mobility Group (HMG) protein, SOX4. Recombinant protein encoded by ESX (for epithelial-restricted with serine box) exhibits Ets-like DNA binding specificity in electrophoretic mobility shift assays and, in transient transfection assays, transactivates Ets-responsive promoter elements including that found in the HER2/neu oncogene. ESX is located at chromosome 1q32 in a region known to be amplified in 50% of early breast cancers, is heregulin-inducible and overexpressed in HER2/neu activated breast cancer cells. Tissue hybridization suggests that ESX becomes overexpressed at an early stage of human breast cancer development known as ductal carcinoma in situ (DCIS).

Amino Acid Sequence↗

Impaired endothelium-dependent relaxation after cardiac global ischemia and reperfusion: role of warm blood cardioplegia.

OBJECTIVES: Experiments were designed to determine whether coronary endothelial dysfunction after cardiac global ischemia and reperfusion could be prevented by warm blood cardioplegic solution. BACKGROUND: The coronary endothelium produces endothelium-derived relaxing factor (EDRF) to prevent vasospasm and thrombosis. After ischemia and reperfusion, endothelium-dependent relaxation (EDR) is diminished as a result of G-protein dysfunction. METHODS: Dogs were exposed to extracorporeal circulation in 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The heart was ischemic for 120 min while continuous warm blood cardioplegic solution (group 1) or intermittent cold (4 degrees C) crystalloid cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 min of reperfusion. RESULTS: Endothelium-derived relaxation in response to acetylcholine, adenosine diphosphate and sodium fluoride of the coronary rings of group 1 was significantly different from that of groups 2 and 3 but was not significantly different from that of group 4. In contrast, EDR in response to the receptor-independent calcium ionophore agonist A23187 was not significantly different between the four groups. Scanning electron microscopic studies showed that platelet adhesion and aggregation, area of microthrombi, disruption of endothelial cells and separation of the intercellular junction could be found in coronary segments of groups 2 and 3 but not in vessels of groups 1 and 4. CONCLUSIONS: These experiments suggest that cardiac global ischemia and reperfusion impair receptor-mediated release of EDRF from the coronary endothelium with G-protein dysfunction. This type of coronary endothelial dysfunction can be prevented by continuous anterograde infusion of warm blood cardioplegic solution during global ischemia.

Animals↗

Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors.

In cell cultures, the key residues associated with HIV-1 resistance to cyclic urea-based HIV-1 protease (PR) inhibitors are Val82 and Ile84 of HIV-1 PR. To gain an understanding of how these two residues modulate inhibitor binding, we have measured the Ki values of three recombinant mutant proteases, I84V, V82F, and V82F/I84V, for DMP323 and DMP450, and determined the three-dimensional structures of their complexes to 2.1-1.9 A resolution with R factors of 18.7-19.6%. The Ki values of these mutants increased by 25-, 0.5-, and 1000-fold compared to the wild-type values of 0.8 and 0.4 nM for DMP323 and DMP450, respectively. The wild-type and mutant complexes overall are very similar (rms deviations of 0.2-0.3 A) except for differences in the patterns of their van der Waals (vdw) interactions, which appear to modulate the Ki values of the mutants. The loss of the CD1 atom of Ile84, in the I84V mutant complexes, creates a hole in the S1 subsite, reducing the number of vdw contacts and increasing the Ki values. The V82F mutant binds DMP323 more tightly than wild type because the side chain of Phe82 forms additional vdw and edge-to-face interactions with the P1 group of DMP323. The Ki values of the single mutants are not additive because the side chain of Phe82 rotates out of the S1 subsite in the double mutant (the chi 1 angles of Phe82 and -182 in the V82F and V82F/I84V mutants differ by 90 and 185 degrees, respectively), further reducing the vdw interactions. Finally, compensatory shifts in the I84V and V82F/ I84V complexes pick up a small number of new contacts, but too few to offset the initial loss of interactions caused by the mutations. Therefore, our data suggest that variants persist in the presence of DMP323 and DMP450 because of a decrease in vdw interactions between the mutant proteases and inhibitors.

Azepines↗

Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.

Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR. The design strategy for these inhibitors is based on the hypotheses that (i) the hydrogen-bonding interactions between the inhibitor and the protease backbone will remain constant for wild-type and mutant enzymes and (ii) inhibitors which are capable of forming many nonbonded interactions, distributed throughout the active site, will experience a lower percent change in binding energy as a result of mutation in the target enzyme than those that form fewer interactions by partial occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved level of high potency against a range of mutant strains of HIV with resistance to a wide variety of HIV protease inhibitors.

Amides↗

Impaired endothelium-dependent relaxation of human hepatic arteries after preservation with the University of Wisconsin solution.

OBJECTIVE: To evaluate the effect of University of Wisconsin solution on endothelium-dependent relaxation and contraction of human hepatic arteries in vitro. DESIGN: Human hepatic arteries were harvested from 24 patients with hepatocellular carcinoma who had undergone hepatectomy. SETTING: A tertiary care center. INTERVENTIONS: Human hepatic arteries (n = 6 in each group) were harvested during resection for hepatocellular carcinoma. The arteries in group 1 (i.e., the control group) were immediately studied without preservation. The arteries in group 2 were preserved in cold (4 degrees C) physiological solution for 1 hour, while the arteries in groups 3 and 4 were preserved in University of Wisconsin solution for 1 and 16 hours, respectively. Segments of control and preserved hepatic arteries with or without endothelium were then suspended in organ chambers to measure the isometric force. RESULTS: The relaxation of segments of the hepatic arteries with endothelium in response to acetylcholine and adenosine diphosphate was significantly (P < .05) greater than that of segments without endothelium. The maximal relaxation of hepatic arterial segments with endothelium in groups 3 and 4 in response to acetylcholine was notably different from that of segments in groups 1 and 2. The maximal relaxation of hepatic arterial segments with endothelium in groups 3 and 4 in response to adenosine diphosphate was notably different from that of segments in groups 1 and 2. Perfusate hypoxia (mean +/- SD PO2, 30 +/- 5 mm Hg) caused the endothelium-dependent contraction of the arteries (the median initial tension in groups 1, 2, 3, and 4 was 251%, 233%, 276%, and 260%, respectively; P > .05). CONCLUSIONS: The endothelium-dependent relaxation of human hepatic arteries in response to acetylcholine and adenosine diphosphate was notably attenuated by University of Wisconsin solution. The impaired endothelium-dependent relaxation by University of Wisconsin solution and the prominent endothelium-dependent contraction of human hepatic arteries would favor vasospasm and thrombosis after hepatic transplantation.

Adenosine↗

Prenatal sonographic diagnosis of single umbilical artery.

PURPOSE: We evaluated the reliability of prenatal sonography and the usefulness of the umbilical vein and artery diameter ratio, transverse umbilical artery diameter, and systolic-diastolic ratio in detecting single umbilical artery (SUA). METHODS: In 24 of 6,970 fetuses, SUA was detected using prenatal sonography and confirmed at birth. These cases were retrospectively reviewed. RESULTS: Four fetuses had major malformations, and 1 had a minor anomaly. Thirteen fetuses with SUA underwent chromosomal analysis, and only 2 had abnormal karyotypes. Most of the SUA fetuses had a normal systolic-diastolic ratio. CONCLUSIONS: Our retrospective study determined that the prognosis of SUA fetuses is good when there is no concurrent anatomic or chromosomal abnormality. Although some reports claim that the transverse umbilical artery diameter or the ratio between umbilical vein and artery diameters can predict SUA, we found no significant improvement in the recognition of SUA using these parameters.

Adult↗

Use of dynamic capillaroscopy for studying cutaneous microcirculation in patients with diabetes mellitus.

To investigate the relationship between cutaneous microcirculation and retinopathy in diabetes mellitus, we studied by dynamic capillaroscopy 35 diabetes mellitus patients, including 10 patients without retinopathy, 10 patients with background retinopathy, and 15 patients with proliferative retinopathy. We found that (1) cutaneous and retinal microcirculation in diabetes mellitus in long-term diabetes mellitus, regressional rather than proliferational changes occurred in skin vasculature as compared to that in retina; (2) functional impairments of cutaneous microcirculation, that is, decreased resting capillary blood cell velocity, peak blood cell velocity, and prolonged time to peak capillary blood cell velocity by dynamic capillaroscopy, could be detected in diabetes mellitus patients without retinopathy; (3) the degree of tortouosity of capillaries, impairment in peak capillary blood cell velocity, and time to peak capillary blood cell velocity of cutaneous microcirculation were significantly correlated with the gravity of retinopathy in diabetes mellitus patients; (4) abnormal leakage of fluorescence in cutaneous microcirculation appeared in diabetes mellitus patients with or without abnormal fluorescein angiography in retina. In conclusion, dynamic capillaroscopy used in concert with ophthalmoscopy and fluorescein angiography can facilitate a comprehensive examination of vasculopathy in diabetes mellitus.

Adult↗

Evaluation of contrast media for bronchography.

BACKGROUND: Bronchography is occasionally needed for the evaluation and management of some congenital pulmonary anomalies as well as some acquired diseases, usually of the tracheo- bronchial tree. There is currently no effective, approved contrast agent for this imaging techniq ue. OBJECTIVE: We evaluated five agents (barium sulfate, iohexol, propyliodone oily, propyliodone aqueous, and perflubron) in terms of image quality, histologic changes, and effects on hemodynamics, blood gases, and standard laboratory tests in New Zealand White rabbits. MATERIALS AND METHODS: Animals were anesthetized and intubated. Each contrast agent (0.25 ml/kg) was administered intratracheally. Three animals in each group had intravenous lines placed for blood sampling and blood pressure monitoring and were sacrificed at 1 h. An additional three animals for each agent were sacrificed at 24 h and 1 week after imaging. Blood samples were taken immediately before contrast instillation and at 1 h postbronchography. Fluoroscopic images were recorded on standard VHS video tape and evaluated in blind fashion. Segments of lung tissue and bronchi were obtained for histologic examination. RESULTS: Necrosis and/or inflammatory infiltrates were noted in 78 % of the bronchograms performed with propyliodone aqueous, 67 % with propyliodone oily, 55 % with perflubron, and 33 % with iohexol 120, 240 and 350. No histologic damage was observed with barium. The propyliodones gave the best-quality imaging results and the most histologic changes. Iohexol, in any concentration, gave the least acceptable images and a moderate number of histologic changes. Barium sulfate demonstrated acceptable images with virtually no histologic changes. CONCLUSION: From the histologic and imaging results, barium is the best available contrast material for bronchography.

Animals↗

Predicting birth weight by fetal upper-arm volume with use of three-dimensional ultrasonography.

OBJECTIVE: Our purpose was to determine the usefulness and accuracy of the three-dimensional ultrasonography assessed fetal upper-arm volume in predicting birth weight. STUDY DESIGN: From June 1996 to October 1996, we performed a prospective study of ultrasonography on 105 pregnant women without fetal structural anomaly or aneuploidy. Both the traditional two-dimensional ultrasonographic parameters and three-dimensional ultrasonography for fetal upper arm volume were measured within 48 hours of delivery. RESULTS: The upper arm volume correlated well with birth weight (r = 0.92, n = 105, p < 0.0001). With use of linear and polynomial regression, we obtained a best-fit new formula, Birth weight = 1088.60 + 36.024 x Upper-arm volume. The accuracy of this new formula is compared with that of two Chinese equations predicting fetal weight reported before and other formulas commonly used in the world as well. Our formula is more accurate in predicting birth weight than all the other formulas by traditional two-dimensional ultrasonography, either in error, percentage error, or absolute error. Another group by prospective validation further proved this finding. CONCLUSION: The upper-arm volume assessed by three-dimensional ultrasonography can accurately predict birth weight, and its accuracy is superior to the previous, formulas. Our study has at least validated the application of upper-arm volume by three-dimensional ultrasonography in estimating fetal weight. Further larger series are needed to confirm our findings.

Adult↗

Video-assisted thoracoscopic operation for interruption of patent ductus arteriosus in adults.

BACKGROUND: Patent ductus arteriosus (PDA) is a frequent congenital heart disease encountered in premature neonates, infants, and children. Video-assisted endoscopic techniques have been used in PDA interruption since 1993. Almost all the experiences are in pediatric patients. Applications in adults with PDA have been limited. METHODS: We report our experience of video-assisted thoracoscopic surgical ligation of PDA in adults. From August 1995 to January 1996, 60 patients with PDA were operated on with a video-assisted thoracoscopic technique. Twelve adults were identified with mean age of 30 years (range, 20 to 57 years). With the patient under general anesthesia and double-lumen endotracheal intubation, two 5-mm holes were made in the left lateral chest wall. Another 4-cm incision was made in the left third intercostal space for manipulation, dissection, and ligation. Conventional surgical instruments were used except an endoscopic grasper and an endoscopic tube that connected to a video camera. The surgical procedure was viewed on a video screen. Transesophageal echocardiography was used for monitoring during PDA ligation. RESULTS: All patients had successful ligation of the PDA. There was no surgical mortality, but there was one morbidity; transient recurrent nerve injury, which recovered 3 months later. Ten patients were extubated in operative room and 2 patients were extubated 2 hours after the operation. Tube thoracostomy was performed in the first 2 cases; it was omitted thereafter. No patients needed narcotic to control chest pain. Postoperative follow-up by echocardiography showed faint ductal flow in 1 patient without any murmur. All patients were discharged within 3 days after the operation. CONCLUSIONS: Our experience suggests that with refinement of instruments and surgical technique, video-assisted thoracoscopic surgical ligation can be safely applied not only in pediatric patients, but also in adults with PDA.

Adult↗

Video-assisted coronary artery bypass grafting during hypothermic fibrillatory arrest.

BACKGROUND: Hypothermic fibrillatory arrest without aortic cross-clamping is a technique for quieting the heart during coronary artery bypass grafting. This report reviews the preliminary results with this technique in 4 patients having video-assisted coronary artery bypass grafting. METHODS: Four male patients 28.5 to 64.5 years old (mean age, 45.4 years) underwent operation for unstable angina. With video-assisted techniques, coronary artery bypass grafting was performed through a left anterior minithoracotomy with femoral-femoral cardiopulmonary bypass without cross-clamping the aorta. The myocardium was protected by continuous coronary perfusion during hypothermic fibrillatory arrest. RESULTS: A left internal thoracic artery graft was anastomosed to the left anterior descending coronary artery in each patient. The posterior descending branch of the right coronary artery was grafted with a pedicled right gastroepiploic artery in 1 patient. The duration of cardiopulmonary bypass was 72 to 127 minutes (mean duration, 92 +/- 21 minutes). The postoperative course of each patient was uneventful. Follow-up (range, 3.9 to 5.8 months; mean follow-up, 4.9 months) was complete for all patients. There were no late deaths. Coronary angiography showed patent grafts. All patients were in New York Heart Association functional class I or II (mean class, 1.25). CONCLUSIONS: Hypothermic fibrillatory arrest is a simple and effective method of quieting the heart, thereby providing a motionless operative field for video-assisted coronary artery bypass grafting.

Adult↗

Carotid artery and jugular vein ligation with and without hypoxia in the rat.

A continuing concern about the use of extracorporeal membrane oxygenation (ECMO) is the cannulation of the common carotid artery or the internal jugular vein. The authors investigated the changes that might occur in the brain with neck vessel ligation in the normal and the hypoxic rat. Two groups of 60 rats each were studied. The first group was divided into three subgroups of 20 animals each. Subgroup 1 (HH) was hypoxic both 24 hours before and 24 hours after operation. Subgroup 2 (HN) (the ECMO model) was hypoxic before operation and recovered for 24 hours in room air. Subgroup 3 (NN) underwent the entire procedure in room air. For each oxygen environment, four different operations were performed: carotid artery ligation, jugular vein ligation, carotid artery and jugular vein ligation, and dissection of the vessels without ligation (sham). Thus each subgroup was further divided into four sub-subgroups based on the operation performed. Rats were again anesthetized after a 24-hour recovery period and killed using low, blunt cervical dislocation. In the first group of 60 rats, the skull was opened and the brain was carefully removed from the cranial vault and placed in a fixative. The brains were placed in a small magnetic resonance imaging (MRI) head coil in groups of five and scans were obtained to provide T1 and T2 images that correlated with histological sections. MRI scans were reviewed in random, blinded fashion by an imager unaware of how these animals had been treated. The brains were then sectioned coronally at six corresponding levels: frontal, mid and posterior cerebrum, midbrain, pons, and medulla. Histological examination was performed in blinded fashion. The number of lesions (usually ischemic as noted by a decrease in the number of neurons) was totaled for each area of the brain. There were no differences that were consistent or statistically significant in the MR images of brains removed from the head, although it would appear that rats with jugular vein and carotid artery ligation were relatively protected. In the HN group jugular vein ligation was worst, and adding carotid artery ligation was best. In the histological studies the NN group had significantly more lesions than the HH group (P < .01). The second group of 60 rats was divided and treated as the first group in all respects except that MRI was conducted immediately after death on intact heads, and no histological studies were performed. This was done to control for lesions that might have been produced by removal of the brains from the skulls. In this group all findings were right sided. One animal in the HN group showed midcerebral white matter edema after jugular and carotid ligation. Focal anterior cerebral edema was seen in another animal (HH) after isolated carotid ligation. An occipital infarct was found in one animal (HH) after both carotid and jugular ligation. The authors conclude that neck vessel ligation in the hypoxic or normoxic rat causes only occasional and sporadic brain injury much as is seen clinically in newborn ECMO patients.

Animals↗

Continuous antegrade warm blood cardioplegia attenuates augmented coronary endothelium-dependent contraction after cardiac global ischemia and reperfusion.

BACKGROUND: Experiments were designed to evaluate the effect of warm blood cardioplegia on endothelium-dependent contraction of the coronary endothelium after cardiac global ischemia and reperfusion. METHOD: Dogs (n = 12 in each group) were exposed to extracorporeal circulation with the body temperature at 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The ascending aorta was crossclamped for 120 minutes while continuous infusion of warm blood cardioplegec solution (group 1) or intermittent infusion of cold (4 degrees C) crystalloid cardioplegic solution (group 2) was performed via the coronary arteries through the aortic root. Cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 minutes of reperfusion. Reperfused (groups 1, 2, and 3) and control (group 4) coronary arteries were then harvested for study. RESULTS: Perfusate hypoxia caused endothelium-dependent contraction in the arteries of all four groups that could be attenuated by NG-monomethyl-L-arginine (L-NMMA) or L-NMMA plus D-arginine, but not by L-NMMA plus L-arginine or endothelin receptor A and B antagonist PD 145065. The endothelium-dependent contraction results in groups 2 and 3 (75% +/- 4% and 80% +/- 5%, respectively) were significantly greater than those in groups 1 and 4 (15% +/- 3% and 18% +/- 5%, respectively). Scanning electron microscope studies showed that platelet adhesion and aggregation, areas of microthrombi, disruption of endothelial cells, and separation of the intercellular junction could be found in coronary segments from groups 2 and 3, but not in vessels from groups 1 and 4. CONCLUSION: These experiments suggest that global ischemia and reperfusion enhances hypoxia-mediated endothelium-dependent contraction of the coronary endothelium and damages the ultrastructure. These kinds of changes can be prevented by continuous antegrade infusion of warm blood cardioplegic solution during global ischemia.

Animals↗

Thoracoscopic loop ligation of parenchymal blebs and bullae: is it effective and safe?

Surgeons who have gained experience and confidence with video-assisted thoracic surgery are now routinely applying the minimally invasive approach to treat patients with spontaneous pneumothorax. Although the endoscopic stapling device may be a preferred method for resection of parenchymal blebs or bullae, the stapling device is not inexpensive. In an effort to contain costs since we started performing the video-assisted thoracoscopic procedure in chest surgical diseases, we have used a self-made endoscopic loop as an alternative method. It has assisted us in performing bulla ablation in a cost-effective manner. Over a 4-year period (1992 to 1996), we assessed the efficacy of ligating parenchymal blebs and bullae with a self-made endoscopic loop by video-assisted techniques. A total of 263 ligations were performed in 250 patients. Surgical indications included recurrence (n = 146), bilaterality of the disease (n = 13), hemopneumothorax (n = 7), radiologically demonstrated large bulla (n = 9), persistent air leak (n = 52), and nonexpansion of the lung (n = 23). There were no operative deaths. Early postoperative complications included a dislodged endoscopic loop necessitating reexploration in one patient and postoperative minor wound infections in 13. The average postoperative hospitalization was 4.5 days. Two hundred seventeen patients (86.8% of all patients) were followed up for a median of 28 months (1 to 46 months) after the operation. There have been no recurrences to date. Our results showed that thoracoscopic loop ligation is safe and effective in managing blebs and parenchymal bullae, with a lower cost, fewer complications, and a lower recurrence rate than provided by standard surgical techniques. On the basis of our results, we advocate the use of the self-made endoscopic loop for ligation of parenchymal blebs and bulla in patients with spontaneous pneumothorax to achieve a truly cost-effective and minimally invasive thoracoscopic procedure.

Adolescent↗

Three-dimensional ultrasound-assessed fetal thigh volumetry in predicting birth weight.

OBJECTIVE: To compare the accuracy of three-dimensional ultrasound-assessed fetal thigh volumetry in predicting birth weight with that of other commonly used formulas composed of biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) by two-dimensional ultrasound. METHODS: We assessed the thigh volume of 100 fetuses using three-dimensional ultrasound. Meanwhile, their BPD, AC, and FL were measured by two-dimensional ultrasound. All infants were delivered within 48 hours after the ultrasound examinations. From polynomial regression analysis, we generated a best-fit formula for the thigh volume to predict birth weight. The accuracy of this thigh-volume formula was compared with those of three formulas commonly used in the United States. In addition, another group of 50 fetuses was measured for prospective validation. RESULTS: The high volume assessed by three-dimensional ultrasound was highly correlated with birth weight (r = 0.89, n = 100, P < .0001). The best-fit formula for thigh volume to predict birth weight was linear, and it was superior to the other commonly used two-dimensional formulas in predicting birth weight. The predicting error (0 g), percent error (0.7%), absolute error (176.1 g), and absolute percent error (5.8%) of the thigh-volume formula were all smaller than those of the other formulas (n = 100, all P < .05). In addition, the thigh-volume formula predicted birth weight more accurately than the other two-dimensional formulas in the prospective-validation group. The three-dimensional formula had smaller mean values of predicting error (38.6 g), percent error (1.5%), absolute error (160.0 g), and absolute percent error (5.1%) than the two-dimensional formulas (n = 50, all P < or = .001), as well as the smallest variances of the above errors (178.1 g, 5.6%, 84.3 g, and 2.9%, respectively). CONCLUSION: The three-dimensional ultrasound-assessed thigh volume has better accuracy in predicting birth weight than the commonly used formulas by two-dimensional ultrasound, and it may improve fetal weight prediction in clinical practice. However, a large-scale prospective validation study may be needed to confirm our conclusions.

Adult↗

Variable domain structure of kappaIV human light chain Len: high homology to the murine light chain McPC603.

Antibody light chains of the kappa subgroup are the predominant light chain component in human immune responses and are used almost exclusively in the antibody repertoire of mice. Human kappa light chains comprise four subgroups. To date, all crystallographic studies of human kappa light chains were carried out on proteins of the kappaI subgroup. The light chain produced by multiple myeloma patient Len. was of the kappaIV subgroup, it differed by only one residue from the germ-line gene encoded protein. The variable domain fragment of the light chain was crystallized from ammonium sulfate in space group C222(1). The crystal structure was determined by molecular replacement and refined at 1.95 A resolution to an R-factor of 0.15. Protein Len has six additional residues in its CDR1 segment compared to the kappaI proteins previously characterized. The kappaIV variable domain, Len, differs in only 23 of 113 residues from murine kappa light chain McPC603. The RMS deviation upon superimposing their alpha-carbons was 0.69 A. The CDR1 segment of the human and murine variable domains have the same length and conformation although their amino acid sequences differ in 5 out of 17 residues. Structural features were identified that could account for the significantly higher stability of the human kappaIV protein relative to its murine counterpart. This human kappaIV light chain structure is the closest human homolog to a murine light chain and can be expected to facilitate detailed structural comparisons necessary for effective humanization of murine antibodies.

Amino Acid Sequence↗

Three-dimensional ultrasound assessment of fetal liver volume in normal pregnancy: a comparison of reproducibility with two-dimensional ultrasound and a search for a volume constant.

The purposes of this study are to compare the reproducibility of two-dimensional ultrasound (2DUS) and three-dimensional ultrasound (3DUS) in the assessment of fetal liver volume (LV), and to test whether the fetal LV assessed by the traditional method with 2DUS is equal to that with 3DUS in normal pregnancy. If significantly different, we then try to calculate a new constant of fetal LV for the traditional equation from the LV values obtained with 3DUS. In total, 30 normal singleton fetuses with gestational ages ranging from 20 to 30 weeks were included for the reproducibility test and 55 cases ranging from 20 to 31 weeks gestation were enrolled for finding a new volume constant of LV. The results showed that 3DUS is superior to 2DUS in the reproducibility test of fetal LV assessment. Moreover, the LV assessed with the traditional 2DUS method (identified as LV_42) was significantly smaller than that measured with 3DUS (P < 0.001). If the traditional 2DUS equation is to be used, the multiplying factor in the equation for the calculation of LV should be modified to 0.55 (SE = 0.017, N = 55). With the new volume constant, the new derived LV with 2DUS (identified as LV 55) was not different from that with 3DUS (identified as LV_3D). In conclusion, we recommend that 3DUS, instead of 2DUS, should be used for reaching an accurate assessment of fetal LV. Otherwise, applying our new volume constant may be of help in detecting abnormal fetal liver growth when only 2DUS is available.

Female↗