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Biomedical subjects

W Ching

Publications and source records attributed to W Ching.

At least 19 recordsLinked to original sources
PubMed2006

Clinical course after change of immunomodulating therapy in relapsing-remitting multiple sclerosis.

We examined the clinical course after switching disease-modifying therapy (DMT) in patients with relapsing-remitting multiple sclerosis (RRMS). Eighty-five consecutive RRMS patients who received weekly interferon beta-1a (IFN beta-1a) 6 MU i.m. for at least 18 months were enrolled. Baseline annualized relapse rate (ARR) for the 2 years prior to initiating therapy with IFN beta-1a was obtained from charts. All 85 patients received treatment with IFN beta-1a at 6 MU i.m. weekly for 18-24 months (mean 19.7 months). Treatment with IFN beta-1a reduced the mean ARR from 1.41 to 1.23 (P=0.005). All 85 patients were then switched to glatiramer acetate (GA) 20 mg s.c. daily and prospectively followed up for 36-42 months (mean 37.5 months). Patients were switched because of persistent clinical disease activity (n=62) or persistently unacceptable toxicity (n=23) as determined by the treating neurologist. Treatment with GA reduced the mean ARR from 1.23 to 0.53 (P=0.0001). Subgroup analysis showed that in patients who were switched because of lack of efficacy (n=62), the mean ARR was reduced from 1.32 on IFN beta-1a to 0.52 on GA (P=0.0001). In contrast, in patients who switched because of persistent toxicity (n=23), the mean ARR was reduced from 0.61 on IFN beta-1a to 0.47 on GA (P, non-significant). Our observations suggest that clinical observations such as relapse rate and tolerability may be used as criteria for switching DMT in clinical practice. More definitive consensus criteria incorporating magnetic resonance imaging and clinical observations for defining optimal response and tolerability need to be developed for the routine clinical management of RRMS patients receiving DMT.

Adjuvants, Immunologic↗
PubMed2005

Production of recombinant protein Pap31 and its application for the diagnosis of Bartonella bacilliformis infection.

Tropical bartonellosis is a highly fatal epidemic and endemic infectious disease that occurs throughout the communities of the Andes Mountains in South America. The disease is caused by the facultative intracellular bacteria, Bartonella bacilliformis. The emergence of bartonellosis in new geographic areas and an increase in the number of reported cases suggest the need for a rapid test for epidemiologic study and investigation of the disease burden. The objective of this research is to develop a rapid serologic diagnostic test using recombinant antigens to overcome the limitations of the current standard IFA technique for laboratory diagnosis. Western blot analysis with patient sera of whole cell lysate separated on a 2D gel identified Pap31 as a dominant antigen. PCR primers were designed according to the sequence of ATCC strain 35685 to amplify the gene coding for Pap31 from a local isolate (HOSP 800-09, Peru). The amplicon was subsequently cloned into pET24a, adding the T7 tag, and expressed in E. coli. Patient sera with different IFA titers confirmed the diagnostic band of 31 kDa on a Western blot of SDS-PAGE. The performance of affinity-purified recombinant Pap31 (rPap31) was also evaluated in an ELISA format with 137 patient sera of known IFA titers. The range of ELISA reading from positive sera did not overlap with the range of those from negative sera, suggesting the potential application of rPap31 in both ELISA for high throughput regional hospital settings and in the construction of handheld rapid tests for rural clinical sites.

Antigens, Bacterial↗
PubMed2003

Intercaudate nucleus ratio as a linear measure of brain atrophy in multiple sclerosis.

Intercaudate nucleus ratio (ICR) is a linear measure of brain atrophy that does not require software application and is independent of image acquisition techniques. The authors examined the relationship between ICR and disability in 190 patients with MS. The results show that ICR correlates with Expanded Disability Status Scale score (r = 0.67; p = 0.0001) and disease duration (r = 0.32; p < 0.01). Intercaudate ratio appears to be a reliable and reproducible linear measure of brain atrophy and correlates with disability and disease duration in MS.

Adult↗
PubMed2001

Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin.

Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction.

Aging↗
PubMed2000

Antibodies to phosphatidylethanolamine and phosphatidylserine are associated with increased natural killer cell activity in non-male factor infertility patients.

Antiphospholipid antibodies (APA) have been identified in patients with recurrent pregnancy loss and IVF failure. Of these, antiphosphatidylethanolamine (aPE) and antiphosphatidylserine (aPS) may have special significance. A link between increased natural killer cell activity (NKa+) and trophoblast cell apoptosis has also been reported. This study was undertaken to determine how the APA profile was associated with peripheral NK cell activity. We evaluated 197 female IVF candidates for APA and NKa. Eighty-nine patients (45%) were APA+ and of these, 51 (57%) were aPE/aPS+. Fifty-four patients (27%) had increased NK cell activity. Some 51% of APA+ and 78% of aPE/aPS+ patients had increased NK cell activity compared with 8% and 13% when APA and aPE/aPS tested negative respectively (P: < 0.0001). Non-male factor infertility patients were APA+ and NKa+ in 57% and 34% of cases respectively, compared with 19% and 13% if a pure male factor was present. Some 88% of aPE/aPS+, non-male factor patients had increased NK cell activity, compared with 12% who tested aPE/aPS negative (P: < 0.0001) and 25% of aPE/aPS+, isolated male factor patients (P: < 0.0001). These findings establish a direct relationship between APA (specifically aPE/aPS) and increased peripheral NK cell activity among non-male factor infertility patients. It is possible that APA do not directly cause reproductive failure but rather function as markers or intermediaries for an underlying, abnormal activation of cellular immunity.

Adult↗
PubMed1998

The use of combined heparin/aspirin and immunoglobulin G therapy in the treatment of in vitro fertilization patients with antithyroid antibodies.

PROBLEM: To compare the effect of heparin/aspirin therapy alone vs. heparin/aspirin in combination with intravenous immuno-globulin (IVIg) immunotherapy on in vitro fertilization (IVF) outcome of patients who test positive for antithyroid antibodies (ATAs). METHOD OF STUDY: Eighty-two women younger than 40 years of age whose infertility was related exclusively to female causes were evaluated. All tested positive for organ-specific antithyroid antibodies (antimicrosomal and/or antithyroglobulin antibodies), but negative for antiphospholipid antibodies. Thirty-seven of these women (group A) received H/A alone, whereas 45 (group B) received heparin/aspirin in combination with IVIg. RESULTS: Ten (27%) of women in group A and 23 (51%) of women in group B achieved live births after completion of a single IVF/embryo transfer cycle (P = 0.027). CONCLUSION: We conclude that IVIg therapy significantly improves IVF success rates in ATA+ women.

Adult↗
PubMed1998

A rational basis for the use of combined heparin/aspirin and IVIG immunotherapy in the treatment of recurrent IVF failure associated with antiphospholipid antibodies.

PROBLEMS: 1) Does the administration of heparin and aspirin (H/A) in combination with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF) implantation and birth rates in patients with recurrent IVF failure? 2) Is the effect of such treatment related to the antiphospholipid antibody (APA) status of the patients concerned? METHOD OF STUDY: Subjects consisted of 89 women younger than 36 years of age whose infertility was a result of causes other than male infertility and who had experienced four or more failed IVF/embryo transfer procedures. Fifty-two women were APA+ (group A), and 37 were APA- (group B). All patients, regardless of their APA status, received H/A (5000 U sq bid), aspirin (81 mg po qd) from the inception of menotropin therapy along with IVIG (20 g) through a single infusion 3 to 10 days before egg retrieval. RESULTS: Twenty-two (42%) of group A and 7 (19%) of group B patients achieved live births (P = 0.020). CONCLUSIONS: IVF outcome is significantly improved when H/A and IVIG are administered to APA+ women with repeat IVF failures. APA- women do not seem to benefit from such treatment.

Adult↗
PubMed1998

The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody-positive women undergoing in vitro fertilization.

PROBLEM: The effect of mini-dose heparin/aspirin (H/A) alone vs. combined intravenous immunoglobulin G (IVIg) and H/A on in vitro fertilization (IVF) birthrates in women who test seropositive for antiphospholipid antibodies (APA+) was evaluated, as was the question of whether outcome is influenced by the gammaglobulin isotype(s) or the phospholipid (PL) epitope(s) to which the APAs are directed. METHOD OF STUDY: A case-control study was conducted in three phases, spanning a 4-year period, in a multicenter clinical research environment. Six hundred eighty-seven APA+ women, who were younger than 40 years and who each, completed up to three consecutive IVF/embryo transfer cycles within a 12-month period, were given either H/A alone or H/A in combination with IVIg. Birthrates relative to the type of immunotherapy (i.e., H/A alone and H/A with IVIg) and APA profile were the main outcome measurements. RESULTS: In phase I, 687 women who tested APA+ to one or more PL epitopes underwent two or fewer IVF attempts for a total of 1050 IVF cycles. Four hundred seventy-seven (46%) births occurred in 923 IVF cycles in which H/A alone was administered. Twenty-two (17%) births occurred after 127 IVF cycles in which H/A was not administered. In phase II, 322 of 687 women tested positive for a single APA subtype. These subjects underwent up to two consecutive IVF attempts for a total of 521 IVF cycles while receiving H/A alone. The birthrate was significantly lower for women whose APAs were directed toward phosphatidylethanolamine (PE) or phosphatidylserine (PS) involving IgG or IgM isotypes than for women who had any other APA (17% vs. 43%). In phase III, 121 women who did not achieve live births after two consecutive IVF attempts in which H/A alone was administered received IVIg in combination with H/A during their third consecutive IVF cycle. The birth rate was 41% after these IVF cycles when anti-PS or anti-PE involving IgG or IgM isotypes were present, as compared with 17% when H/A alone was administered. The IVF outcome did not improve when IVIg was administered in association with any other single APA. CONCLUSIONS: The treatment of APA+ women with H/A alone improves IVF birthrates. This benefit is selective in that it does not apply in cases in which IgG- or IgM-related APAs are directed against PE or PS. In such cases, the addition of IVIg significantly improves the outcome.

Abortion, Habitual↗
PubMed1998

Correlation between beta 2-glycoprotein antibodies and antiphospholipid antibodies in patients with reproductive failure.

PROBLEM: Antiphospholipid antibodies (APAs) are important in the etiology of reproductive failure. Studies have shown that binding proteins are necessary for the detection of APAs. One of these, beta 2-glycoprotein, has been shown to be necessary for detection of anticardiolipin antibodies. It is felt that some APAs may be directed to the binding protein itself, or to a combination of the binding protein and phospholipid. METHOD OF STUDY: In this study, a comparison of APAs vs. anti beta 2-glycoprotein antibodies was performed on the sera of 123 women younger than 40 years of age with a history of reproductive failure. Antibodies to six phospholipid epitopes, cardiolipin, phosphatidyle-thanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol, and phosphatidylserine, were measured. RESULTS: Of the 123 women tested, 33 had one or more positive immunoglobulin (Ig)G antibodies to phospholipids, of which 9 were to cardiolipin. However, only 1 of 123 women had IgG antibodies to beta 2-glycoprotein and she was APA negative. Thirty-eight of 123 women had one or more IgM antibodies to phospholipids, with none directed to cardiolipin IgM. In contrast, only 8 of the 123 women had IgM antibodies to beta 2-glycoprotein. Five of the eight patients had IgM APA; 4 of 5 had IgM antibodies to PE, 1 to PI. CONCLUSIONS: There is no correlation between beta 2-glycoprotein antibodies and APA status in this population. To date, our most sensitive test for detecting phospholipid autoimmune-mediated in vitro fertilization failure still appears to be the ELISA assay for APA.

Adult↗
PubMed1997

The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination.

We have investigated the potential role of contactin and contactin-associated protein (Caspr) in the axonal-glial interactions of myelination. In the nervous system, contactin is expressed by neurons, oligodendrocytes, and their progenitors, but not by Schwann cells. Expression of Caspr, a homologue of Neurexin IV, is restricted to neurons. Both contactin and Caspr are uniformly expressed at high levels on the surface of unensheathed neurites and are downregulated during myelination in vitro and in vivo. Contactin is downregulated along the entire myelinated nerve fiber. In contrast, Caspr expression initially remains elevated along segments of neurites associated with nascent myelin sheaths. With further maturation, Caspr is downregulated in the internode and becomes strikingly concentrated in the paranodal regions of the axon, suggesting that it redistributes from the internode to these sites. Caspr expression is similarly restricted to the paranodes of mature myelinated axons in the peripheral and central nervous systems; it is more diffusely and persistently expressed in gray matter and on unmyelinated axons. Immunoelectron microscopy demonstrated that Caspr is localized to the septate-like junctions that form between axons and the paranodal loops of myelinating cells. Caspr is poorly extracted by nonionic detergents, suggesting that it is associated with the axon cytoskeleton at these junctions. These results indicate that contactin and Caspr function independently during myelination and that their expression is regulated by glial ensheathment. They strongly implicate Caspr as a major transmembrane component of the paranodal junctions, whose molecular composition has previously been unknown, and suggest its role in the reciprocal signaling between axons and glia.

Animals↗
PubMed1995

A comparison of flow cytometry and microcytotoxicity for the evaluation of alloimmune therapy in patients with recurrent spontaneous abortions.

PROBLEM: There is substantial data that support the efficacy of paternal leukocyte immunization (PLI) for the treatment of alloimmune mediated miscarriage; however, there is confusion regarding the laboratory test that should be performed to determine levels of maternal anti-paternal leukocyte antibodies (MAPLA). METHOD: Popular methodologies employed include: 1) microcytotoxicity (MCX), 2) mixed lymphocyte culture (MLC), and 3) cell flow cytometry crossmatch (FCXM). Cell flow cytometry crossmatch correlates well with the more difficult MLC assay although the former proves the more sensitive study. This work compares the MCX assays with FCXM. The study group consisted of ten women who had a history of three or more spontaneous abortions (SABs). All ten had very low levels (< 10%) of MAPLA as measured by FCXM. Following PLI all subjects demonstrated elevated levels (> 50%) of MAPLA by FCXM. At 12 weeks gestation, sera were simultaneously measured for MAPLA by MCX and FCXM. RESULTS: Although all ten patients had very high levels of MAPLA by FCXM during pregnancy, five of ten had antibodies to HLA Class I and two of ten had antibodies to HLA Class II paternal antigens by MCX. Furthermore, all patients who were positive by MCX to paternal Class I antigens were also positive to Class I antigens not seen in either parent. Both patients who were positive by MCX to paternal Class II antigens were also positive to maternal Class II antigens. Notable is that all ten women eventually delivered healthy infants. CONCLUSION: Based on this preliminary study, the MCX assay is neither sensitive or reliable enough to determine the need and/or to monitor the effectiveness of PLI. Flow cytometry should be the modality of choice when determining the need for alloimmunotherapy and to monitor the effectiveness of treatment.

Abortion, Habitual↗
PubMed1994

High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin.

This study was undertaken to explore whether intervention with heparin and aspirin (H/A) in selected patients undergoing in-vitro fertilization (IVF) and embryo transfer could improve fecundity rates. Specifically, it explored the possibility that women diagnosed with organic pelvic disease who demonstrated antiphospholipid antibodies (APA) could benefit from H/A administration in a similar manner to that used in patients with recurrent pregnancy loss. We used an enzyme-linked immunosorbent assay for six different phospholipids to identify patients who expressed APA before they underwent IVF/embryo transfer. This study was confined to the first IVF/embryo transfer cycle that followed assessment of APA status and accordingly, the number of IVF/embryo transfer cycles corresponds with the number of patients treated. APA seropositive patients were treated with aspirin, 81 mg orally q.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 of controlled ovarian stimulation. The endpoint for success was a live birth or an ultrasound confirming fetal cardiac activity (a viable pregnancy). The prevalence of APA in patients diagnosed with organic pelvic disease (53%) was much higher than in those without female pathology (14%). The administration of H/A to APA seropositive patients significantly (P < 0.05) improved the viable pregnancy rate (49%) compared to the untreated APA seropositive group (16%). The viable pregnancy rate for APA seropositive women treated with H/A was also significantly (P < 0.001) higher than for untreated APA seronegative patients (27%). We conclude that all women undergoing IVF/embryo transfer should be tested for APA prior to initiating ovarian stimulation and those with APA seropositivity should be treated with H/A.

Adult↗
PubMed1994

Characterization of antiphospholipid antibodies in women with recurrent spontaneous abortions.

Antiphospholipid antibodies are important in the etiology of recurrent pregnancy loss. To date, most studies have concentrated on antibodies to cardiolipin specifically. In this study, the serum of 352 women with recurrent pregnancy loss was studied by enzyme-linked immunosorbent assay for antibodies to six phospholipid epitopes: cardiolipin, phosphoserine, phosphoglycerol, phosphoethanolamine, phosphatidic acid and phosphoinositol. Of these women, 59.1% had either an IgG or IgM antibody to one of the six phospholipids. This compared to only 4.6% in the control group. Approximately 75% of the isotypes were IgM. The most common phospholipid epitope was phosphoserine. However, in patients with antibodies to only one phospholipid, phosphoethanolamine was the most common. These findings support recent evidence that antiphospholipid antibodies may interfere with the formation of syncytiotrophoblasts in the placenta. In addition, antiphospholipid antibodies occur more frequently in patients who suffer recurrent miscarriages than was previously thought.

Abortion, Habitual↗
PubMed1991

Age-dependent extrasynaptic modulation of axonal conduction by exogenous and endogenous GABA in the rat optic nerve.

To ascertain whether endogenous gamma-aminobutyric acid (GABA) exists and exerts physiological effects in the optic nerve, we compared the effects of GABA and related drugs on the neonatal (1 to 22 days of age) and adult (greater than 6 months) rat optic nerve in vitro. GABA (10(-4)-10(-3) M) reversibly depressed the amplitude and increased the latency of compound action potentials in the neonatal optic nerve. In the adult optic nerve, GABA (10(-4)-10(-3) M) had no significant effect on the compound action potential. The GABA-A receptor agonist, isoguvacine (10(-4)-10(-3) M), mimicked these GABA effects on the neonate and adult optic nerve. Lower concentrations (10(-5) M) of GABA increased excitability of the neonatal optic nerve but produced no discernible effects on the adult optic nerve. The GABA-uptake inhibitor, nipecotic acid (10(-3) M), mimicked the effects of GABA (10(-5) M) on the neonatal optic nerve. The GABA-A receptor blockers, picrotoxin and bicuculline (10(-6)-10(-3) M), decreased the latency of compound action potentials in the neonatal optic nerve. Membrane potential recordings indicate that while GABA (10(-5)-10(-3) M) depolarized the neonatal optic nerve dose-dependently, picrotoxin hyperpolarized the axons. In the adult optic nerve, neither GABA-uptake inhibitors nor GABA-A receptor blockers had significant effects on the compound action potential. These results suggest that functional GABA-A receptors and GABA are present in the neonatal rat optic nerve and depolarize axons under physiological conditions. However, this does not appear to be the case in the adult optic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

The effect of silicon nitride ceramic on rabbit skeletal cells and tissue. An in vitro and in vivo investigation.

This article presents a morphologic assessment of the effect of silicon nitride ceramic (Si3N4) on rabbit marrow stromal cells and their differentiation when grown in vitro and in vivo. In vitro marrow stromal cells (MSC) attached initially to upper portions of ceramic discs. However, at four weeks, cells only attached to disc edges. Fresh marrow or first passage MSC, inoculated into diffusion chambers with and without Si3N4, formed cartilage, bone, and fibrous tissue after being implanted intraperitoneally for five weeks. Tissue differentiated adjacent to Si3N4 but not within the pores. In contrast, Si3N4 implants inserted into femoral marrow cavities were surrounded initially by woven bone and within three months by mature bone that had permeated implants with a pore size of 255 +/- 64 microns. Plugs having a pore diameter of 170 +/- 45 microns mainly contained vascularized fibrous tissue with occasional foci of osteoid or bone in the peripheral pores. In a pilot experiment, three femoral segmental Si3N4 endoprostheses were implanted in three adult rabbits, and the osseous reactions were monitored during their natural life. Each implant was enclosed by a stable cuff of bone within four months of implantation and remained unchanged during the rest of the animal's life. Autopsies confirmed these roentgenographic observations, and tissue appositional to each prosthesis was morphologically normal. Si3N4 has the potential of an important ceramic for use in osseous reconstruction.

Animals↗