Biomedical subjects

C C Chu

Publications and source records attributed to C C Chu.

At least 109 records · Page 6Linked to original sources

PubMed1993

Interleukin 5 induces S mu-S gamma 1 DNA rearrangement in B cells activated with dextran-anti-IgD antibodies and interleukin 4: a three component model for Ig class switching.

The cellular signals required for induction of immunoglobulin (Ig) class switching are only partially understood. Two processes that are considered to be necessary for such induction are DNA synthesis and germline constant heavy (CH) gene transcription. We now show that an additional signal, as mediated by interleukin 5 (IL-5), is also required. To induce proliferation of resting B cells, but not Ig secretion, we utilized anti-IgD antibodies conjugated to dextran (alpha delta-dex). The addition of IL-4, a well-established switch factor for the IgG1 subclass, to alpha delta-dex-activated cell cultures failed to induce IgG1 secretion or mIgG1+ cells unless IL-5 was also present. While IL-4 stimulated an increase in germline gamma 1 RNA in alpha delta-dex-activated cells, this effect could neither be induced nor enhanced by IL-5. By contrast, IL-5 strongly enhanced steady-state levels of productive gamma 1 RNA induced by alpha delta-dex and IL-4, suggesting that IL-5 stimulated IgG1 switch rearrangement. To test this possibility we measured switch (S) mu-S gamma 1 DNA recombination events using a newly developed assay, digestion circularization polymerase chain reaction (DC-PCR). We demonstrated that IL-5 was necessary for induction of S mu-S gamma 1 DNA rearrangement in alpha delta-dex plus IL-4-activated cells but that it had little effect on rearrangement in the absence of IL-4. Our data strongly suggest, therefore, a three-component model for induction of Ig class switching. This model includes germline CH gene transcription, DNA synthesis, and a third component that is necessary for recombination.

Animals↗

PubMed1993

DNA rearrangement can account for in vitro switching to IgG1.

During immune responses, B lymphocytes may switch from the expression of immunoglobulin M (IgM) to the expression of another isotype (e.g., IgG, IgE, IgA). In stable hybridomas and myelomas expressing a "switched" (S) isotype, DNA deletions between S mu and a "downstream" S region (S region recombination) have been found. In primary B cells, studies of the molecular basis of switching have been limited by the ability to sensitively quantitate the amount of DNA deletion; such studies would be of interest because other nondeletional mechanisms (trans-splicing, alternative processing of a long transcript) have been proposed to account for isotype switching in certain circumstances. We have applied the digestion-circularization polymerase chain reaction (DC-PCR) technique to measure the amount of S region recombination that occurs in the course of class switching in primary B lymphocytes. Resting B cells were cultured in lipopolysaccharide (LPS) and interleukin 4 (IL-4) to stimulate switching to IgG1. These cells begin to express membrane IgG1 at day 2.5 of culture and reach maximum expression by day 4.5. DNA was prepared from cultured cells and analyzed for S mu-S gamma 1 rearrangement by DC-PCR. Chimeric switch regions, indicating S mu-S gamma 1 recombination, were detected in amounts that, in most cases, correlated with surface expression. Furthermore, when cells were sorted on the basis of surface IgG1 expression, a mean of at least one S mu-S gamma 1 rearrangement per cell was seen in five out of seven experiments. In general, the IgG1+ cells obtained at 4.5 and 5.5 d of culture had close to 2 S mu-S gamma 1 rearrangements per cell. In IgG1- cells, S mu-S gamma 1 rearrangements were detectable, but at frequencies substantially lower that in IgG1+ cells. Thus, these results indicate that DNA deletion accompanies class switching in normal B cells stimulated with LPS and IL-4.

Animals↗

PubMed1993

A comparison of a new polypropylene suture with Prolene.

The purpose of this paper is to examine the performance of the newly available monofilament polypropylene suture (Surgipro) manufactured by U.S. Surgical and compare it with commercial Prolene sutures for determining the merit of this new suture. Two different sizes of Surgipro sutures were used. They were 4/0 and 0 sizes and were tested in terms of their fundamental properties: level of crystallinity, melting temperature, fiber morphology, and mechanical properties including knot strength and knot security. The effect of three different sterilization methods on the mechanical and fundamental properties of the new polypropylene (PP) sutures was also examined. In general, the new Surgipro sutures performed as good as Prolene sutures in terms of mechanical properties; but there were some differences in fundamental properties between these two types of PP sutures, particularly in finer size PP sutures. The major differences were in interior fiber morphology, level of crystallinity, and melting temperature. Surgipro suture fibers showed homogeneous interior morphology, while Prolene fibers exhibited two distinctive fiber morphologies. These two types of PP suture fibers also responded differently to the three sterilization methods tested. Surgipro sutures are less affected by different sterilization methods than the same size Prolene control. Except for the Co 60 gamma sterilization, Surgipro suture fibers did not exhibit statistically significant differences in tensile breaking strength between sterilized and control. Ethylene oxide and autoclave sterilized Prolene suture fibers, however, showed statistically (p less than 0.05) consistently lower tensile breaking strength than their unsterilized controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallization↗

PubMed1993

Hydrolytic degradation and morphologic study of poly-p-dioxanone.

The in vitro hydrolytic degradation of 2-0 size PDS monofilament suture was studied for the purpose of revealing its morphologic structure and degradation mechanism. The sutures were immersed in phosphate buffer of pH 7.44 for up to 120 days at 37 degrees C. These hydrolyzed sutures were examined by the changes in tensile properties, weight, thermal properties, x-ray diffraction structure, surface morphology, and dye diffusion phenomena. It was found that hydrolysis had significant effects on the change of PDS fiber morphology and properties. Hydrolysis, however, had no significant effect on overall molecular orientation of the fiber until the very late stage. PDS suture fibers retained their skeleton throughout the earlier periods of hydrolysis concurrent with mass and tensile strength losses. PDS sutures exhibited an absorption delay of 120 days. Both heat of fusion and melting point exhibited a maximum function of hydrolysis time. Hydrolysis of PDS suture fibers proceeded through two stages: random scission of chain segments located in the amorphous regions of microfibrils and intermicrofibrillar space, followed by stepwise scission of chain segments located in the crystalline regions of microfibrils. Dye diffusion data showed that the passage along the longitudinal direction of the fiber was relatively easier than the lateral direction as evident in the diffusion coefficient, activation energy, and flexibility of chain segments. Swiss-cheese model of fiber structure appears to describe the observed dye diffusion phenomena and their dependence on hydrolysis time and dying temperature.

Adsorption↗

PubMed1993

Bicomponent vascular grafts consisting of synthetic absorbable fibers. I. In vitro study.

The objective of this study is to determine the effects of the location and concentration of synthetic absorbable yarn components in bicomponent vascular graft fabrics on their structure and properties in a controlled in vitro hydrolytic environment. Bicomponent vascular fabrics were made from Dacron and polyglycolic acid (PGA) yarns with a range of composition ratios of PGA to Dacron and a range of locations of PGA. Both woven and single jersey knit fabrics were made. These fabrics were characterized by standard textile methods and subject to in vitro hydrolytic degradation study. In vitro hydrolytic degradation study showed that the most dramatic changes in the bicomponent fabric characteristics and properties occurred 30 and 60 days of hydrolysis. This schedule coincided with the hydrolytic degradation rate of PGA absorbable sutures. In the woven (W) group, the incorporation of absorbable yarns in the weft direction (W3) of the bicomponent fabrics resulted in the velour-like, loose, and porous surface morphology of the fabric for potential subsequent tissue ingrowth, while those woven fabrics with absorbable yarns in the warp direction (W1) did not have this unique velour-like surface. In the knitted (K) group, the concentration of absorbable yarns appeared to be closely related to the observed changes in fabric properties and structure. The incorporation of absorbable yarns into knitted fabrics did not result in the same level change in fabric structure and property as woven fabrics. In both W and K groups, a minimal level of mechanical strength of the fabrics was maintained due to the remaining Dacron yarns. Structural integrity of these fabrics was retained at the end of hydrolytic degradation study. The data obtained could be used to correlate with the subsequent in vivo performance of these bicomponent vascular grafts. If correlations exist, they could be used to improve the design of future bicomponent vascular grafts for improved performance.

Absorption↗

PubMed1993

Effect of a combined gamma irradiation and Parylene plasma treatment on the hydrolytic degradation of synthetic biodegradable sutures.

The aim of this study was to alter the hydrolytic degradation property of synthetic absorbable suture fibers so that their mass loss would occur at a shorter time without significantly compromising their tensile strength loss profile. A two-step treatment concept (gamma-irradiation followed by Parylene plasma deposition) was introduced for achieving this aim. Vicryl and Maxon were used as the model compounds to test this new concept. After the treatment, the in vitro hydrolytic degradation properties of Vicryl and Maxon were evaluated by weight loss, tensile breaking strength, heat of fusion and melting temperature, intrinsic viscosity, surface wettability, and surface morphology. The results suggested that gamma-irradiation at a dosage level between 0.2-2.0 Mrad for Vicryl sutures and about 2.0 Mrad for Maxon sutures were the most effective dosages to accelerate the suture mass loss. The subsequent Parylene plasma deposition treatment statistically significantly improved the retention of tensile strength for both gamma-irradiated Vicryl and Maxon sutures and hence counteracted the undesirable gamma-irradiation induced acceleration of tensile strength loss. However, this second-step Parylene plasma treatment extended the suture mass loss to longer periods. These findings were consistent with the observed surface wettability, surface morphology, intrinsic viscosity, and thermal properties. A thin hydrophobic Parylene skin layer wrapped around a suture was responsible for the slower rate in mass and strength loss. This outer skin layer acted as a barrier to not only water but also degradation fragments.

Biodegradation, Environmental↗

PubMed1993

Genetic and molecular analyses of the C-terminal region of the recE gene from the Rac prophage of Escherichia coli K-12 reveal the recT gene.

The nucleotide sequence of the C-terminal region of the recE gene of the Rac prophage of Escherichia coli K-12 reveals the presence of a partially overlapping reading frame we call recT. Deletion mutations show that recT is required for the RecE pathway of conjugational recombination. By cloning recT with a plasmid vector compatible with pBR322, we showed by cis-trans tests that the portion of the recE gene encoding ExoVIII DNA nuclease activity is also required for RecE pathway conjugational recombination. The recT gene can replace the redB gene of lambda for recA-independent plasmid recombination. A Tn10 insertion mutation previously thought to be in recE is located in recT and is renamed recT101::Tn10. Discrepancies between the molecular mass estimates of wild-type ExoVIII protein determined from mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and calculated from the predicted amino acid sequence are discussed. The hypothesis that wild-type ExoVIII protein results from fusion of RecE and RecT proteins is disproved genetically, thus supporting a previous hypothesis that the discrepancies are due to abnormal protein mobility in SDS-PAGE. A computer-performed scan of the bacteriophage nucleotide sequence data base of GenBank revealed substantial similarity between most of recE and a 2.5-kb portion of the b2 region of lambda. This suggests interesting speculations concerning the evolutionary relationship of lambda and Rac prophages.

Amino Acid Sequence↗

PubMed1992

Quantitation of immunoglobulin mu-gamma 1 heavy chain switch region recombination by a digestion-circularization polymerase chain reaction method.

B lymphocytes expressing surface IgM with or without IgD may switch to the expression of other isotypes (IgG, IgA, or IgE) in the course of immune responses. Analyses of genomic DNA from cloned myelomas and hybridomas have shown that the isotype switch is accompanied by a rearrangement characterized by deletion of DNA between the switch (S) region of the mu gene and that associated with the new isotype, resulting in the formation of a composite S region. Measurement of this deletional rearrangement has been difficult in populations of normal B cells but would be useful for investigating the mechanism of the rearrangement and determining whether deletional rearrangement is responsible for all instances of class switching. We have developed a sensitive assay for deletional rearrangement that we designate the digestion-circularization polymerase chain reaction (PCR). In this assay, genomic DNA is digested with a restriction enzyme that recognizes sites that flank the recombined composite S region. The digested DNA is then ligated at low concentrations to favor the formation of circles. The ligation joins the 5' and 3' ends of each restriction fragment, making it possible to amplify by PCR across the ligated restriction site by using appropriate primers. From DNA that has undergone deletional rearrangement, a single-sized PCR product is produced and can be quantitated. We demonstrate here that the digestion-circularization PCR assay can detect S mu-S gamma 1 rearrangements in B cells cultured with lipopolysaccharide and interleukin 4. The assay is sensitive enough to quantitate switched cells constituting only 1-2% of the population.

Animals↗

PubMed1992

An antisense oligonucleotide complementary to a sequence in I gamma 2b increases gamma 2b germline transcripts, stimulates B cell DNA synthesis, and inhibits immunoglobulin secretion.

An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the gamma 2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4. It is also a striking stimulant of DNA synthesis by resting B cells. The antisense S-oligonucleotide causes a 10-20-fold increase in the expression of the gamma 2b germline transcript. Among mutants of the antisense S-oligonucleotide, some show all the effects whereas others are inactive. A similar hierarchy exists in the quantitative biological activities of mutant S-oligonucleotides and in their capacity to hybridize to the sense oligonucleotide, strongly suggesting that an I gamma 2b sequence in the RNA transcript or in the noncoding strand of the DNA is the target of the antisense S-oligonucleotide. The possible relationship of the overexpression of the germline gamma 2b transcript to the biological functions of the I gamma 2b antisense S-oligonucleotide is discussed.

Animals↗

PubMed1992

Plasma surface modification of synthetic absorbable sutures.

The aim of the study was to examine the feasibility of using plasma surface modification technology to alter the hydrolytic degradation rate of commercial synthetic absorbable sutures. Size 2-0 Dexon, Vicryl, PDSII, and Maxon sutures were tested. They were treated by two different surface modification techniques: parylene deposition and plasma gases (Methane, trimethylsilane, and tetrafluoroethene). The thickness of surface treatment ranged from 200 to 1000 A. The treated sutures were subject to in vitro hydrolytic degradation in phosphate buffer of pH = 7.4 at 37 degrees C for up to 120 days. The tensile breaking strength, weight loss, surface wettability, bending stiffness, and surface morphology were evaluated. The results indicated that the concept of plasma surface treatment for altering the hydrolytic degradation of synthetic absorbable sutures was feasible, and the level of improvement depended on the type of sutures, the treatment conditions, and the duration of hydrolysis. Vicryl and PDSII sutures showed overall the best improvement in tensile strength retention among the four commercial sutures. Dexon and Maxon sutures, however, exhibited only marginal improvement. The observed improvement in tensile strength retention appeared to be related to the increasing hydrophobicity of the sutures. The surface treatments did not adversely affect the bending stiffness of the sutures and no visible surface morphological changes were observed. Refinements and optimization of the surface treatment conditions are needed for achieving the maximum advantage of the proposed concept, particularly shielding the harmful effect of uv during plasma treatment.

Biodegradation, Environmental↗

PubMed1991

EEG spectral analysis and topographic mapping in Wilson's disease.

Computerized EEG spectral analysis and topographic mapping were performed on 14 patients with Wilson's disease (WD) and 10 normal subjects of comparable ages. The predominant EEG changes in WD were diffuse but uneven topographic abnormalities with a decrease in alpha activity, an increase in theta and delta activities, and a low voltage background mainly in the alpha frequency band. Eleven patients (80%) had at least one of the above EEG changes. Furthermore, topographic mapping provided more clearly defined foci of slowing and epileptiform activity. Patients with cerebral white matter involvement, akinetic-rigid syndrome, dystonia, or psychiatric symptoms tended to have more abnormal EEGs. It is concluded that EEG changes in WD are common and the quantitative EEG analysis can increase the likelihood of detecting mild or even subtle EEG abnormalities in individual patients as well as in the patient group.

Adolescent↗

PubMed1991

Comparative effects of omega-3 and omega-6 polyunsaturated fatty acids on protein metabolism in rats bearing the mammary adenocarcinoma.

The comparative effects of diets containing 20% (wt/wt) of either fish oil (FO) or safflower oil (SO) on protein synthesis and catabolism were determined in rats bearing the 7,12-dimethylbenz(a)anthracene (DMBA) 13762 mammary adenocarcinoma in vivo using a 6-hour constant infusion of L-(1-14C)-leucine. Tumor-bearing animals fed FO had significantly lower tumor growth rate (36 +/- 0.5 v 53 +/- 0.7%/d, P less than .05), total tumor protein synthesis (Ts) (1.25 +/- 0.1 v 1.85 +/- 0.1 mumol/h, P less than .05), and tumor protein concentration (12.0 +/- 0.5 v 14.0 +/- 0.7%/d, P less than 0.01). Tumor fractional synthetic rate and total protein breakdown rate of the tumor were unaffected by FO feeding. Both tumor-bearing and saline-control animals fed FO had significantly (P less than .01) lower liver fractional synthetic rate and total protein breakdown rate, and higher liver total protein compared with SO-fed rats. Muscle protein kinetics were unaffected by either treatment or diet. Whole body protein kinetics were not affected by dietary treatment, but the presence of tumor significantly (P less than .001) reduced whole body flux, synthesis, breakdown, and oxidation. Chronic FO feeding for 7 weeks significantly (P less than .001) lowered omega-6 polyunsaturated fatty acids (omega-6 PUFAs) and significantly elevated omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (P less than .001) in both plasma phospholipid and triglycerides. The present study indicates that dietary FO can modulate mammary tumor growth in a manner that reflects changes in protein metabolism in both host and tumor tissues.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Bromocriptine in augmentation of antipsychotic response in chronic schizophrenia: a negative pilot report.

To further assess the usefulness of bromocriptine in treatment of schizophrenia seven inpatient chronic schizophrenics with acute exacerbation who had failed to respond to four weeks of antipsychotic therapy were treated with bromocriptine 2.5 mg daily for a treatment duration varying from one dose to four weeks while their antipsychotic dose was continued unchanged. Mean age of patients was 38.9 +/- 11.6 years and mean number of prior psychiatric hospitalizations was 12.0 +/- 7.2. Patients were rated with the Brief Psychiatric Rating Scale prior to the first bromocriptine dose, at 24 hours after dosage initiation, and at weekly intervals. One patient showed clinically significant improvement in both positive and negative schizophrenic symptoms. One patient showed slight improvement in unusual thought content, and four patients were clinically unchanged. One patient significantly worsened after the first dose. Factors possibly contributing to response and non-response are discussed. This is a report of an open study in 7 patients. It is the only report of bromocriptine treatment in patients previously shown unresponsive to antipsychotics and whose antipsychotics dose was held constant throughout the study. Addition of bromocriptine to the antipsychotic regimen remains an unproven treatment approach which may be considered only in patients refractory to or inadequately controlled with antipsychotics.

Adult↗

PubMed1991

A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia.

BACKGROUND: Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory. METHOD: To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale. RESULTS: No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders. CONCLUSIONS: The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition.

Adolescent↗

PubMed1991

Buspirone in the treatment of posttraumatic stress disorder.

Three patients with a DSM-III-R diagnosis of posttraumatic stress disorder were successfully treated with buspirone in final maximum dosages ranging from 35-60 mg daily. The onset of clinical efficacy ranged from 5-29 days. Symptoms that improved included anxiety, insomnia, flashbacks, and depressed mood. Patients experienced no side effects. Serotonin partial agonist effects are a possible mechanism underlying buspirone's efficacy.

Aged↗

PubMed1990

Physical analysis of spontaneous and mutagen-induced mutants of Escherichia coli K-12 expressing DNA exonuclease VIII activity.

We have mapped the extents of two deletion sbcA mutations which result in production of DNA exonuclease VIII (ExoVIII). One mutation, sbcA8, deletes about 140 kb of DNA which includes most of the Rac prophage and the trg gene. Western blot analysis shows that the protein produced is larger than wild type ExoVIII. The nucleotide sequence shows that a translational gene fusion has occurred. The N-terminal 294 codons of recE have been deleted and the remaining C-terminal codons have been fused to the N-terminal portion of another reading frame we call sfcA. Analysis of the protein sequence encoded by sfcA shows an 83% similarity with rat and mouse NADP-linked malic enzyme. We discuss the possibility that sfcA is identical to maeA which encodes NAD-linked malic enzyme from Escherichia coli. Restriction nuclease analysis of a second deletion, sbcA81, by Southern blot technique indicates that about 105 kb of DNA have been deleted and a transcriptional gene fusion has occurred between recE and the regulatory region of an E. coli chromosomal gene. We also examined eight other sbc mutations that result in ExoVIII production. Five have no effect on restriction nucleotide fragment sizes detected by complementarity to lambda rev as probe. These are presumed point mutations. Three seem to produce additional restriction nucleotide fragments complementary to lambda rev. The possible nature of these sbc mutations is discussed.

Amino Acid Sequence↗

PubMed1990

Glutaraldehyde in collagen gel formation.

The effect of glutaraldehyde (GTA) on the course of collagen gel formation was studied by measuring the absorbance against time. It was found that the t1/2 of fibril formation decreased with the addition of GTA and reached a minimum at a concentration of 6 microliters of GTA per g of collagen. For GTA concentrations, [GTA], above this value, t1/2 increased again and fibril formation was inhibited at concentrations of about 50-60 microliters of GTA per g of collagen. Thermal analysis showed that the denaturation temperature was the highest for the gels formed with [GTA] of 6 microliters/g, the transition peak also being the sharpest. At this [GTA], the compressive rigidity of the gels was also the highest. For low [GTA], above and below the optimum value, the fibrils formed had the normal collagen periodicity when observed in the electron microscope. This study shows that collagen gels which find applications as biomaterials can be effectively crosslinked at the gelation stage itself by the addition of low concentrations of GTA.

Biocompatible Materials↗

PubMed1990

The effect of culture on the sex differences in schizophrenia.

Cultural influences on sex differences in clinical characteristics and symptomatology of schizophrenia were studied among 369 schizophrenic patients from the United States and Turkey. Male schizophrenics were more likely to be single, and were younger than female schizophrenics at onset of symptoms and when first diagnosed, treated and hospitalised in both cultures. Turkish male and female schizophrenics were more ambivalent, inappropriate, "silly", euphoric, depersonalised, dissociated, mute, conceptually disorganised, and exhibiting more flight of ideas and thought than American male and female schizophrenics. Irrelevant thought and stereotypic behaviour were most severe in Turkish male and American female schizophrenics. Hallucinatory behaviour was most intense in Turkish separated, divorced, or widowed female schizophrenics and American married male schizophrenics. Turkish married female and Turkish separated, divorced, or widowed male schizophrenics were most disoriented. Turkish single female schizophrenics were most mute. Turkish separated, divorced, or widowed male schizophrenics showed most intense stupor behaviour.

Adult↗