PubMed Health⌕ Search

Biomedical subjects

S Ho

Publications and source records attributed to S Ho.

At least 37 records · Page 2Linked to original sources

Generation of interferon alpha-producing predendritic cell (Pre-DC)2 from human CD34(+) hematopoietic stem cells.

Upon viral stimulation, the natural interferon (IFN)-alpha/beta-producing cells (IPCs; also known as pre-dendritic cells (DCs 2) in human blood and peripheral lymphoid tissues rapidly produce huge amounts of IFN-alpha/beta. After performing this innate antiviral immune response, IPCs can differentiate into DCs and strongly stimulate T cell-mediated adaptive immune responses. Using four-color immunofluorescence flow cytometry, we have mapped the developmental pathway of pre-DC2/IPCs from CD34(+) hematopoietic stem cells in human fetal liver, bone marrow, and cord blood. At least four developmental stages were identified, including CD34(++)CD45RA(-) early progenitor cells, CD34(++)CD45RA(+) late progenitor cells, CD34(+)CD45RA(++)CD4(+)interleukin (IL)-3Ralpha(++) pro-DC2, and CD34(-)CD45RA(++) CD4(+)IL-3Ralpha(++) pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-alpha/beta upon viral stimulation and to differentiate into DCs in culture with IL-3 and CD40 ligand. CD34(++)CD45RA(-) early progenitor cells did not have the capacity to produce large amounts of IFN-alpha/beta in response to viral stimulation; however, they can be induced to undergo proliferation and differentiation into IPCs/pre-DC2 in culture with FLT3 ligand.

Antigens, CD34↗

A GDP-fucose-protected, pyridoxal-5'-Phosphate/NaBH(4)-sensitive lys residue common to human alpha1-->3Fucosyltransferases corresponds to Lys(300) in FucT-IV.

Human alpha1-->3/4fucosyltransferases (FucTs) contain a common essential pyridoxal-5'-phosphate(PLP)/NaBH(4) reactive, GDP-fucose-protectable Lys. For identification, site-directed mutants at lysines of FucT-IV and -VII were prepared and tested. Non conserved lysine mutants K119Y and K394Q were similar to wild-type FucT-IV. However, mutants of conserved lysines K228R and K300R were distinct. The specific activity of K228R was 2- to 3-fold lower but retained K(m) values for donor and acceptor substrates as wild-type FucT-IV. The specific activity of K300R was reduced over 400-fold with an apparent K(m) for GDP-fucose over 200 microM. FucT-VII mutants K169R and K240R (equivalent to K228R and K300R for FucT-IV, respectively) were inactive. No change in PLP/NaBH(4) sensitivity occurred with K119Y, K228R, and K394Q compared to wild-type FucT-IV. These and previous results (A. L. Sherwood, A. T. Nguyen, J. M. Whitaker, B. A. Macher, M. R. Stroud, and E. H. Holmes, J. Biol. Chem. 273, 25256-25260, 1998) demonstrate that of three conserved lysines in FucT-IV, two (Lys(228) and Lys(283)) are not involved in substrate binding but perhaps in catalysis. The third site, Lys(300), is involved in GDP-fucose binding and PLP/NaBH(4) inactivation.

Amino Acid Sequence↗

The human anti-bullous pemphigoid monoclonal autoantibody P22 is encoded by genes of the IGHV4 and IGLV4 families.

We identified, cloned, and biochemically characterized the full-length cDNAs encoding the heavy and light chains of a human monoclonal antibody (mAb) from the Epstein-Barr virus (EBV)-cell line P22. The cell line P22, which originated from a patient with bullous pemphigoid (an autoimmune disease causing skin blistering) expressed immunoglobulin-G (IgG) with a lambda light chain. Although the variable heavy (IGHV) chain gene family could not be assigned by IGHV repertoire analysis, the determination of its nucleotide sequence demonstrated that the heavy chain of P22 belonged to the IGHV4 family. The limited IGHV4 gene usage by memory IgG, IGA and IgE-expressing cells supports the notion of the autoreactivity-associated IGHV4 genes and stresses the strong selection pressure within germinal centres towards IGHV4 family. Alignment of P22 IGHV4 cDNA sequence to germline sequences from gene databases, revealed a remarkable divergence, suggesting that the heavy chain of the P22 mAb encodes a distinct IGHV4 gene. The variable light chain (IGLV) encodes a IGLV4 gene and is 98% similar to a previously reported IGLV gene. Furthermore, fluorescent staining with the recombinant mAb showed the same reactivity to that of the native antibody. The data reported herein, (a) reveal an autoantibody encoding a distinct IGHV4 gene, (b) confirm the notion that autoantibodies preferentially use IGHV4 genes, and (c) hypothesize that somatic hypermutation within GC may be a mechanism by which autoreactive B lymphocytes escape negative selection.

Amino Acid Sequence↗

Joint position during anterior-posterior glide mobilization: its effect on glenohumeral abduction range of motion.

OBJECTIVE: To investigate the effect of joint position during an anterior-posterior glide (APG) procedure on the range of motion (ROM) of glenohumeral abduction in cadaver specimens. DESIGN: Mechanical simulation of APG mobilization and abduction torque ROM measurement of the glenohumeral joint with a material testing system. The immediate mechanical efficacy of APG was compared in two groups of specimens at two different joint positions: midrange (n = 5) and end range (n = 6) of glenohumeral abduction. SETTING: Biomechanics laboratory. SPECIMENS: Eleven fresh cadaver shoulder specimens (mean age, 66.9+/-2.5 yrs). MAIN OUTCOME MEASURE: Improvement in glenohumeral abduction torque ROM obtained before and after APG procedure. RESULTS: Glenohumeral abduction improved significantly, as indicated by a significant increase (Kruskal-Wallis statistics, chi2 = 7.50, p = .006) in the torque ROM of the end range group (mean +/- standard error of the mean, 2.02 degrees +/- .20 degrees) over the midrange group (.64 degrees +/- .08 degrees). A significant difference in the magnitude of peak displacement of the humeral head between midrange (14.44+/-3.56 mm) and end range (3.19+/-.81 mm) groups was also found (Mann-Whitney test, p < .030). CONCLUSION: This study demonstrated that APG technique performed at close to the end of the range of abduction is more effective in improving glenohumeral abduction ROM than that performed at the middle of the range of abduction.

Aged↗

Immediate response of glenohumeral abduction range of motion to a caudally directed translational mobilization: a fresh cadaver simulation.

OBJECTIVE: To investigate the immediate effect of caudal glide translational mobilization on the range of motion (ROM) of passive glenohumeral abduction with a fresh cadaver model to simulate the mobilization movement performed by a physical therapist treating patients with glenohumeral hypomobility. DESIGN: Mechanical simulation of caudal glide mobilization and abduction torque range of motion (TROM) measurement of the glenohumeral joint with 2 material testing systems. Mobilizations were conducted with the glenohumeral joint positioned at a resting position (IGR) and at the end range of abduction (IGE). SETTING: Biomechanics laboratory. CADAVERS: Twenty fresh shoulder specimens from 10 cadavers (mean age, 68 +/- 8 yr). MAIN OUTCOME MEASURE: Changes in TROM of the glenohumeral abduction in response to 5 bouts of caudal glide mobilization. RESULTS: At least 3 repetitions of TROM were required to attain consistent measurements on glenohumeral abduction ROM. Significant differences were found among changes in TROM because of rest, IGR, and IGE (Kruskal-Wallis statistics, (chi2 = 14.58, p = .001). A greater increase in glenohumeral abduction TROM was found after IGE (mean +/- standard error of the mean, 4.38 degrees +/- 0.95 degrees) compared with the rest control (0.03 degrees +/- 0.07 degrees; Mann-Whitney test, p = .001, alpha = .017) or its IGR counterpart (0.26 degrees +/- 0.46 degrees, p = .001, alpha = .017). CONCLUSION: This simulation of caudal glide translational mobilization at the end range using cadaver models improved passive glenohumeral abduction ROM but was ineffective when performed with the shoulder placed in a resting position. The mechanical responses of the glenohumeral joint to translational mobilization in a live patient may be similar, but some caution should be used in generalizing these findings.

Aged↗

Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice.

AIMS: The tumour marker CA19-9 has been promoted as a reliable test for the detection of pancreatobiliary malignancy, yet its diagnostic role remains poorly defined. In this study the clinical interpretation of a raised serum CA19-9 level has been evaluated, with particular reference to obstructive jaundice. METHODS: One hundred and sixty-four patients with a CA19-9 level above 33 U/ml were studied. Serum CA19-9 was compared with clinical diagnosis and correlated with serum bilirubin level. In a subgroup of jaundiced patients (16 benign and 15 malignant cases), follow-up CA19-9 levels were determined 2 weeks after biliary drainage. RESULTS: The median CA19-9 level was lower in benign cases (102 (IQR 50-264) U/ml) than those with pancreatobiliary tumours (910 (IQR 263-6170) U/ml; P<0.01), although the overlap was substantial. In benign jaundiced cases, a positive correlation was observed between bilirubin and CA19-9 elevation (R=0.41, P<0.01). Relief of jaundice was associated with a fall in CA19-9 level in all benign cases and in nine of the 15 with malignancy. CONCLUSION: Confident discrimination between benign and malignant disease could not be made on the basis of a solitary elevated CA19-9 measurement. Hyperbilirubinaemia was associated with a further deterioration in specificity and caution is warranted when interpreting the results in jaundiced patients. Overall, only one half of patients with an elevated CA19-9 level ultimately proved to harbour a malignancy.

Adult↗

Cryptotia.

Explore the source record for details and available documents.

Child↗

Vegetarianism and ischemic heart disease in older Chinese women.

OBJECTIVE: This study compared the risk of ischemic heart disease among older vegetarian Chinese women with that of older non-vegetarian women. METHODS: 90 vegetarian Chinese women over 70 years old in Hong Kong were screened for ischemic heart disease by electrocardiogram (ECG) and cardiovascular questionnaire. They were compared with 90 non-vegetarian women of similar age examined in a previous local survey. The effects of confounding factors were adjusted by stepwise logistic regression analysis. RESULTS: The percentages of subjects with ischemic heart disease defined by symptoms and ECG or by ECG alone were significantly lower in vegetarian women (p <0.005 and p<0.05 respectively). Vegetarians had lower serum cholesterol levels: more were old age home residents and were less likely to perform regular exercise. On stepwise logistic regression, using probable ischemic heart disease defined by questionnaire and ECG as outcome measure, vegetarianism was the only significant predictor (OR 0.3, 95%CI 0.1-0.6, p<0.005). CONCLUSIONS: Vegetarian older Chinese women had lower risk of ischemic heart disease when compared with non-vegetarians. Apart from lower serum cholesterol levels, vegetarianism may have other protective factors against ischemic heart disease.

Age Factors↗

Factors critical to the design and execution of epidemiologic studies and description of an innovative technology to follow the progression from normal to cancer tissue.

The results obtained from experimental studies of estrogen carcinogenesis need validation in epidemiologic studies. Such studies present additional challenges, however, because variations in human populations are much greater than those in experimental systems and in animal models. Because epidemiologic studies are often used to evaluate modest differences in risk factors, it is essential to minimize sources of errors and to maximize sensitivity, reproducibility, and specificity. In the first part of this chapter, critical factors in designing and executing epidemiologic studies, as well as the influence of sample collection, processing, and storage on data reliability, are discussed. One of the most important requirements is attaining sufficient statistical power to assess small genetic effects and to evaluate interactions between genetic and environmental factors. The second part of this chapter describes innovative technology, namely, Fourier transform-infrared (FT-IR) spectra of DNA that reveal major structural differences at various stages of the progression from normal to cancer tissue. The structural differences become evident from wavenumber-by-wavenumber statistical comparisons of the mean FT-IR spectra of DNA from normal to cancer tissues. This analysis has allowed distinguishing benign tissues from cancer and metastatic tissues in human breast, prostate, and ovarian cancers. This analysis, which requires less than 1 microg of DNA, is predicted to be used for detecting early cancer-related changes at the level of DNA, rather than at the cellular level.

DNA, Neoplasm↗

Automatic optimization of resting and exercise atrioventricular interval using a peak endocardial acceleration sensor: validation with Doppler echocardiography and direct cardiac output measurements.

Peak endocardial acceleration (PEA) measured by an implantable acceleration sensor inside the tip of a pacing lead reflects ventricular filling and myocardial contractility. The contribution of the plateau phase of PEA as an indicator of optimal ventricular filling, hence of the appropriate atrioventricular interval (AVI) at rest and during exercise, was studied in 12 patients (age 69 +/- 6 years) with complete AV block and a PEA sensing DDDR pacemakers (Living 1 Plus, Sorin Biomedica). At a mean resting heart rate of 79 +/- 15 beats/min, the mean AVI optimized by PEA versus Doppler echocardiography (echo) were identical (142 +/- 37 vs 146 +/- 26 ms, P = 0.59). During submaximal exercise at a mean heart rate of 134 +/- 6 beats/min, AVI optimized by PEA was 135 +/- 37 ms. Cardiac output at rest, measured by the CO2 rebreathing method, was comparable with AVI determined by echo versus PEA (4.3 +/- 2.9 and 3.7 +/- 2.4 L/min, respectively), and increased to the same extent (8.0 +/- 3.9 vs 8.3 +/- 5.2 L/min) during submaximal exercise. In patients with AV block, AVI automatically set by PEA was comparable with AVI manually optimized by Doppler echocardiography and was associated with comparable exercise induced hemodynamic changes.

Aged↗

The nature of the principal type 1 interferon-producing cells in human blood.

Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.

CD40 Ligand↗

Activity patterns and synaptic organization of ventrally located interneurons in the embryonic chick spinal cord.

To investigate the origin of spontaneous activity in developing spinal networks, we examined the activity patterns and synaptic organization of ventrally located lumbosacral interneurons, including those whose axons project into the ventrolateral funiculus (VLF), in embryonic day 9 (E9)-E12 chick embryos. During spontaneous episodes, rhythmic synaptic potentials were recorded from the VLF and from spinal interneurons that were synchronized, cycle by cycle, with rhythmic ventral root potentials. At the beginning of an episode, ventral root potentials started before the VLF discharge and the firing of individual interneurons. However, pharmacological blockade of recurrent motoneuron collaterals did not prevent or substantially delay interneuron recruitment during spontaneous episodes. The synaptic connections of interneurons were examined by stimulating the VLF and recording the potentials evoked in the ventral roots, in the VLF, or in individual interneurons. Low-intensity stimulation of the VLF evoked a short-latency depolarizing potential in the ventral roots, or in interneurons, that was probably mediated mono- or disynaptically. At higher intensities, long-latency responses were recruited in a highly nonlinear manner, eventually culminating in the activation of an episode. VLF-evoked potentials were reversibly blocked by extracellular Co2+, indicating that they were mediated by chemical synaptic transmission. Collectively, these findings indicate that ventral interneurons are rhythmically active, project to motoneurons, and are likely to be interconnected by recurrent excitatory synaptic connections. This pattern of organization may explain the synchronous activation of spinal neurons and the regenerative activation of spinal networks when provided with a suprathreshold stimulus.

Activity Cycles↗

Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord.

We examined the effects of spontaneous or evoked episodes of rhythmic activity on synaptic transmission in several spinal pathways of embryonic day 9-12 chick embryos. We compared the amplitude of synaptic potentials evoked by stimulation of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and after episodes of activity. With the exception of the short-latency responses evoked by dorsal root stimulation, the potentials were briefly potentiated and then reduced for several minutes after an episode of rhythmic activity. Their amplitude progressively recovered in the interval between successive episodes. The lack of post-episode depression in the short-latency component of the dorsal root evoked responses is probably attributable to the absence of firing in cut muscle afferents during an episode of activity. The post-episode depression of VLF-evoked potentials was mimicked by prolonged stimulation of the VLF, subthreshold for an episode of activity. By contrast, antidromically induced motoneuron firing and the accompanying calcium entry did not depress VLF-evoked potentials recorded from the stimulated ventral root. In addition, post-episode depression of VLF-evoked synaptic currents was observed in voltage-clamped spinal neurons. Collectively, these findings suggest that somatic postsynaptic activity and calcium entry are not required for the depression. We propose instead that the mechanism may involve a form of long-lasting activity-induced synaptic depression, possibly a combination of transmitter depletion and ligand-induced changes in the postsynaptic current accompanying transmitter release. This activity-dependent depression appears to be an important mechanism underlying the occurrence of spontaneous activity in developing spinal networks.

Animals↗