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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 253 records · Page 14Linked to original sources
PubMed1990

Comparison of secondary failure rate between three second generation sulphonylureas.

Sulphonylureas are effective hypoglycaemic agents but have been reported to have a high failure rate with time. The introduction of a second generation of sulphonylureas may have modified this effect, but little information is available. Two hundred and forty-eight non-insulin dependent diabetic patients were prospectively randomly treated with one of three second generation sulphonylureas--gliclazide (86), glibenclamide (84), and glipizide (78), and were followed for 5 yr to assess the secondary failure rate. Six out of 86 (7%) failed with gliclazide, 15 out of 84 (17.9%) failed with glibenclamide, and 20 out of 78 (25.6%) failed with glipizide. Gliclazide was significantly better than glipizide (p less than 0.005), but not other differences were significant. With all three drugs, in the patients who failed on treatment, body mass index (BMI) at diagnosis was significantly lower than in those who responded to treatment (p less than 0.001). There are differences in secondary failure rate between second generation sulphonylureas. Measurement of the BMI at diagnosis may be useful in predicting those patients most likely to fail to respond.

Blood Glucose↗
PubMed1990

[Inflammatory carcinoma of the uterine cervix. Review of 9 cases].

Nine cases of inflammatory invasive carcinoma of the uterine cervix are reviewed. All appeared in women under less than fifty years old, quickly after normal PAP smears. They occupied the endocervix, which mean diameter was 5 cm and outcome was very poor with only one survivor: four patients were free of disease in the pelvis and relapsed outside, the others underwent a local regional failure in less than 2 years. Association of radiotherapy and surgery is mandatory for stage IB and IIA FIGO; radiotherapy modalities--brachytherapy, external irradiation followed by brachytherapy--must be chosen according to tumor volume, size of the cervix, anatomy of vagina. For other stages radiotherapy alone is recommended using hyperfractionated treatment; in the future such observation would be documented by cytofluorometry analysis and/or molecular biology approach.

Adult↗
PubMed1989

Comparison of myocardial washout rate of thallium-201 between rest, dipyridamole with and without aminophylline, and exercise states in normal subjects.

The myocardial washout rate of thallium-201 was studied in 85 subjects with a less than 5% likelihood of coronary artery disease undergoing rest (group I, n = 12), dipyridamole (group II, n = 24) and exercise (group III, n = 49) stress thallium-201 scintigraphy. Subjects receiving dipyridamole were subdivided into group IIA (n = 11), who received an aminophylline injection 10 minutes after dipyridamole infusion, and group IIB (n = 13), who did not. The mean and highest washout rate values in each of 3 segments in the anterior, 45 degrees and 85 degrees left anterior oblique views were calculated. In group II the mean washout rate of thallium-201 was similar in all segments of each view and the overall mean washout rate did not differ between the 3 views studied. There was a good correlation between the mean and highest washout rate values in individual subjects (r = 0.98, p less than 0.001). The mean +/- standard deviation myocardial 4-hour washout rate of thallium-201 (anterior view) was 10 +/- 6% in group I compared with 40 +/- 14% in group IIA (p less than 0.05 vs group I), 31 +/- 13% in group IIB (p less than 0.05 vs group I) and 54 +/- 11% in group III (p less than 0.05 each vs group IIA and group IIB, respectively). There was a wide variation in mean washout rate values in group II (range 12 to 58%), and this variation was not altered by aminophylline administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Solubilization of SV40 plasma-membrane-associated large tumor antigen using single-phase concentrations of 1-butanol.

The nature of the interaction of the simian virus 40 (SV40) transforming protein, large tumor antigen (T-ag), with the plasma membrane of transformed cells is not well understood. We report here that SV40 plasma-membrane-associated large tumor antigen (pmT-ag) can be solubilized by using single-phase concentrations of 1-butanol. Purified plasma membranes from SV40-transformed mouse cells yielded T-ag when treated with 2.5% butanol; solubilization of T-ag from the purified membranes in butanol was temperature dependent, with approximately 10-fold more T-ag extracted at 37 degrees C than at 22 degrees C; and application of 2.5% butanol to mKSA cells after cellular surface proteins had been radiolabeled with 125I resulted in the release of iodinated T-ag. Butanol-extracted pmT-ag coprecipitated with p53 and several cellular proteins ranging in size from 35 to 60 kDa. One cellular component migrated at a mobility similar to that of tubulin (56 kDa), and a monoclonal antibody against the alpha subunit of tubulin coprecipitated T-ag. Immunoblotting of proteins immunoprecipitated with monoclonal antibodies against T-ag or p53 from butanol extracts with a monoclonal antibody against the beta subunit of tubulin revealed specific coprecipitation of tubulin with T-ag and p53. This suggests that complexes composed of tubulin, T-ag, and p53 exist in butanol extracts. Control experiments eliminated the possibility of an artifactual association of tubulin with T-ag and p53 induced by butanol. Two-dimensional gel analyses revealed that 2.5% butanol at 37 degrees C extracted a subset of membrane-associated proteins and some cytosolic proteins, as well as a number of proteins that were not soluble in either high salt or detergent. Thus, the butanol extraction conditions employed in this study recovered a species of pmT-ag that appears to complex with tubulin. As butanol reportedly is less deleterious to native protein structures than other agents, including high salts and detergents, this extraction procedure may be useful for studying the structure and function of other membrane-associated proteins.

1-Butanol↗
PubMed1989

Characterization of a nondeleterious L1 insertion in an intron of the human factor VIII gene and further evidence of open reading frames in functional L1 elements.

We have characterized an insertional event in IVS-10 of the factor VIII gene in a pedigree containing a hemophilia A patient (JH-25). The inserted DNA is a 5' truncated L1 element that is 681 bp long followed by a 3'66-bp poly(A) tract. The L1 element is inserted 154 bp 5' to the start of exon 11 and is flanked by a 13- to 17-bp target site duplication. The L1 insertion is present in four generations of the patient's family. The maternal grandfather who carries the insertion does not have hemophilia A, indicating that the insertion is not the cause of hemophilia A in the patient. We have sequenced this insertion and two previously reported de novo L1 insertions in the factor VIII gene in patients JH-27 (3785 bp) and JH-28 (2132 bp). The three nucleotide sequences differ by 0.2-0.8%. All three of these L1 insertions have open reading frames (ORFs) (1192, 642, and 157 aa) and the three derived amino acid sequences are 98-99% identical. The previously reported sequence similarity between L1 3' ORFs and the polymerase domain of reverse transcriptases is maintained in the ORFs of the JH-27 and JH-28 L1 insertions. The presence of open reading frames and the close sequence similarity of these recently inserted L1 elements provide indirect evidence for the existence of a set of functional L1 elements that encode one or more proteins necessary for their retrotransposition.

Base Sequence↗
PubMed1989

At least two mutant alleles of ornithine delta-aminotransferase cause gyrate atrophy of the choroid and retina in Finns.

Gyrate atrophy of the choroid and retina (GA) is an inherited chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT; L-ornithine: 2-oxo-acid aminotransferase; EC 2.6.1.13). GA is one of the "Finnish genetic diseases," a group of several rare monogenic disorders that occur with increased frequency in the Finnish population. Using a combination of RNase A protection, genomic cloning, and polymerase chain reaction amplification of genomic DNA, we found one of two missense mutant OAT alleles to be present in each of 16 Finnish GA pedigrees. The first mutation R180T, in which arginine-180 is replaced by threonine, was present in homozygous form in patients from two pedigrees. The second mutation L402P, in which leucine-402 is replaced by proline, was present in homozygous form in patients from 14 pedigrees. Neither mutation was present in 19 Finnish controls. L402P was not present in 18 non-Finnish GA patients but R180T was found in an American GA patient. We constructed full-length mutant cDNAs by amplifying patient cDNA with the polymerase chain reaction and cloning a restriction fragment containing the mutation into an otherwise normal human OAT cDNA. These mutant cDNAs were then expressed in CHO-K1 cells, which lack endogenous OAT. Both R180T and L402P inactivate OAT. These results show molecular heterogeneity in GA alleles even in the Finnish population.

Alleles↗
PubMed1989

Molecular mechanism in the formation of a human ring chromosome 21.

We have characterized the structural rearrangements of a chromosome 21 that led to the de novo formation of a human ring chromosome 21 [r(21)]. Molecular cloning and chromosomal localization of the DNA regions flanking the ring junction provide evidence for a long arm to long arm fusion in formation of the r(21). In addition, the centromere and proximal long arm region of a maternal chromosome 21 are duplicated in the r(21). Therefore, the mechanism in formation of the r(21) was complex involving two sequential chromosomal rearrangements. (i) Duplication of the centromere and long arm of one maternal chromosome 21 occurred forming a rearranged intermediate. (ii) Chromosomal breaks in both the proximal and telomeric long arm regions on opposite arms of this rearranged chromosome occurred with subsequent reunion producing the r(21).

Amnion↗
PubMed1989

Outpatient treatment of PCP abusers.

Despite the persistence of phencyclidine (PCP) abuse as a public health problem in many urban areas of the United States, there are no published data on outpatient treatment outcome. We studied 37 unselected male PCP abusers (mean age 32 years, 73% Black, 19% married, 68% unemployed) who attended at least one outpatient treatment session at the Brentwood Division, West Los Angeles VA Medical Center. Subjects had smoked PCP for an average of 7 years, with 84% using it at least weekly (38% daily) and 76% using other drugs (alcohol, marijuana, or cocaine). All subjects reported psychological dependence on PCP (i.e., liking PCP use and difficulty stopping despite adverse consequences), while none reported a physiological withdrawal syndrome when stopping PCP use. Subjects stayed in treatment an average of 21 weeks (range 1-155 weeks), attending an average of 68% of the group meetings. PCP was detected in weekly urine samples 78% of the time, with verbal self-report of recent PCP use occurring before 29% of the group meetings. Four subjects (11%) achieved at least 1 year of abstinence, 10 (30%) transferred to residential treatment or a community recovery home, 16 (48%) dropped out of treatment, and two (6%) were jailed. Treatment outcome was not significantly associated with subject characteristics. Age was the only subject characteristic that significantly predicted length of stay (r = .40).

Adult↗
PubMed1989

Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene.

We have identified two novel RNA-splicing mutations affecting a critical nucleotide (nt) in the acceptor consensus sequences at both the IVS-1/exon 2 and IVS-2/exon 3 junctions of the human beta-globin gene. Both mutations are single nt substitutions, T to G and C to A, at position -3 adjacent to the invariant AG dinucleotide. For the IVS-2/exon 3 mutation abnormal splicing into the cryptic splice site at IVS-2 nt 579 is documented. Identification of these two mutations provides further support for the importance of the location of specific nucleotides within the consensus sequences in splice site selection and RNA processing.

Base Sequence↗
PubMed1988

Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man.

L1 sequences are a human-specific family of long, interspersed, repetitive elements, present as approximately 10(5) copies dispersed throughout the genome. The full-length L1 sequence is 6.1 kilobases, but the majority of L1 elements are truncated at the 5' end, resulting in a fivefold higher copy number of 3' sequences. The nucleotide sequence of L1 elements includes an A-rich 3' end and two long open reading frames (orf-1 and orf-2), the second of which encodes a potential polypeptide having sequence homology with the reverse transcriptases. This structure suggests that L1 elements represent a class of non-viral retrotransposons. A number of L1 complementary DNAs, including a nearly full-length element, have been isolated from an undifferentiated teratocarcinoma cell line. We now report insertions of L1 elements into exon 14 of the factor VIII gene in two of 240 unrelated patients with haemophilia A. Both of these insertions (3.8 and 2.3 kilobases respectively) contain 3' portions of the L1 sequence, including the poly (A) tract, and create target site duplications of at least 12 and 13 nucleotides of the factor VIII gene. In addition, their 3'-trailer sequences following orf-2 are nearly identical to the consensus sequence of L1 cDNAs (ref. 6). These results indicate that certain L1 sequences in man can be dispersed, presumably by an RNA intermediate, and cause disease by insertional mutation.

Base Sequence↗
PubMed1988

Serum cholesterol and coronary heart disease: Auckland general practitioners' attitudes and practices in 1986.

The relationship between elevated serum cholesterol and coronary heart disease, is now generally accepted as being causal. To examine current attitudes and practices regarding the treatment of high serum cholesterol, questionnaires were sent to a randomly selected sample of general practitioners in the Takapuna health district during 1986. The response rate among the 92 doctors in general practice at the time of the study was 80%. The majority of general practitioners (82.5%) believed that there was a casual relationship between high serum cholesterol and coronary heart disease and that reducing levels would help prevent coronary heart disease. Almost all general practitioners (96%) were screening some groups of patients for high serum cholesterol, with most screening those with symptomatic coronary heart disease or associated risk factors, and 15% screening all patients. Although almost 90% of general practitioners had patients on diet therapy and one third had patients on drug treatment, there was wide variation in attitudes regarding the serum cholesterol levels meriting dietary or drug treatment. This suggests that there is still considerable confusion as to when and how to treat high cholesterol levels and that specific national guidelines for the detection and management of high serum cholesterol are required as part of a comprehensive programme to prevent coronary heart disease.

Adult↗
PubMed1988

Specific suppression of anti-DNA production in vitro.

To investigate the regulation of anti-DNA antibody production, we generated anti-DNA-specific suppressor cells by exposing normal human T cells and a small percentage of adherent cells to high concentrations of DNA. These cells suppressed the production of anti-DNA by both autologous peripheral blood mononuclear cells (PBMC) and allogeneic PBMC derived from systemic lupus erythematosus (SLE) patients. Anti-DNA production was suppressed significantly more than anti-RNA, antitetanus, or total immunoglobulin production. Specific suppression was enhanced by increasing the numbers of DNA-primed CD8+ cells and was obliterated by irradiation of the DNA-primed cells. In contrast to T cells from normal individuals, T cells obtained from two intensively studied SLE patients were unable to generate specific suppressor cells for anti-DNA production in both autologous and allogeneic test systems. Despite this defect, these patients were still capable of generating specific suppressor cells for antibody production directed against an exogenous antigen, tetanus toxoid.

Antibodies, Antinuclear↗
PubMed1988

Oxazepam as a probe of hepatic metabolism in patients with Alzheimer's disease.

1. Hepatic metabolism of oxazepam in Alzheimer's disease (AD) was assessed by measurement of urinary metabolites in a group of hospitalized patients with AD, a hospitalized schizophrenic control group and a normal community based group. 2. A subgroup of six AD patients showed marked elevations of the hydroxylated metabolite. The median excretion of conjugated oxazepam in the AD and schizophrenic patients was almost one third that in normal controls (p less than .005). 3. A relationship between decline in level of conjugated metabolite and increase in the mental confusion score on the London Psychiatric Rating Scale (r = -.5253, p less than .05) was found in the AD patients. 4. Changes in hepatic metabolism in AD may be relevant not only for drug metabolism and the development of side effects, but also for the pathogenesis of AD.

Aged↗
PubMed1988

Genetic linkage map of human chromosome 21.

Two of the most common disorders affecting the human nervous system, Down syndrome and Alzheimer's disease, involve genes residing on human chromosome 21. A genetic linkage map of human chromosome 21 has been constructed using 13 anonymous DNA markers and cDNAs encoding the genes for superoxide dismutase 1 (SOD1) and the precursor of Alzheimer's amyloid beta peptide (APP). Segregation of restriction fragment length polymorphisms (RFLPs) for these genes and DNA markers was traced in a large Venezuelan kindred established as a "reference" pedigree for human linkage analysis. The 15 loci form a single linkage group spanning 81 cM on the long arm of chromosome 21, with a markedly increased frequency of recombination occurring toward the telomere. Consequently, 40% of the genetic length of the long arm corresponds to less than 10% of its cytogenetic length, represented by the terminal half of 21q22.3. Females displayed greater recombination than males throughout the linkage group, with the difference being most striking for markers just below the centromere. Definition of the linkage relationships for these chromosome 21 markers will help refine the map position of the familial Alzheimer's disease gene and facilitate investigation of the role of recombination in nondisjunction associated with Down syndrome.

Chromosome Mapping↗
PubMed1988

The spectrum of beta-thalassaemia mutations in Sicily.

To characterize beta-thalassaemia genes among the Sicilian population we have previously determined the DNA haplotypes in the beta-globin gene cluster of 99 beta-thal chromosomes. We found seven haplotypes, although 95 of 99 beta-thal chromosomes contained framework 1 and framework 3 beta genes. We have now determined the mutation in all 99 of these beta-thal genes by the use of oligonucleotide hybridization. PCR-amplification and direct genomic sequencing, and direct restriction analysis. Our results indicate that (1) the beta (0)-39 mutation is most frequent (35%); (2) beta(0)-39, IVS-1 nt 110 and IVS-1 nt 6 mutations account for 90% of beta-thal genes: (3) the IVS-1 nt 6 mutation is more frequent in thalassaemia intermedia (77%) than in Cooley's disease (34%): (4) the association between haplotypes and specific mutations is imperfect, but mutation spread has occurred within haplotypes containing the same beta-gene framework: (5) the beta(0)-39 and the IVS-1 nt 6 mutations, with a mutation spread to two major haplotypes, may be older than the IVS-1 nt 110 mutation: (6) these data make possible first-trimester prenatal diagnosis in many families (85%) in Sicily using only three pairs of oligonucleotides. In addition, a new mutation, a frameshift at codon 76 due to loss of a C residue, was found in a single beta-thal chromosome.

Child↗
PubMed1988

Isolation of a glucan-binding domain of glucosyltransferase (1,6-alpha-glucan synthase) from Streptococcus sobrinus.

A glucan-binding domain of 1,6-alpha-glucan synthase (dextransucrase) (GTF-S) was isolated from a trypsin digest of the Streptococcus sobrinus enzyme. The large 60.5-kilodalton peptide had an affinity for dextran comparable to that of the native enzyme, but had no glucan synthesis activity. The domain was produced in high yield compared with other large cleavage products, which allowed easy purification by size exclusion high-pressure liquid chromatography and affinity chromatography. Two other proteases (mouse submaxillaris protease and lysyl endopeptidase) with specificities similar to trypsin generated a distribution of GTF-S peptides that was also greatly enriched in the glucan-binding peptide. Proteases with markedly different specificities (chymotrypsin and Staphylococcus aureus V8 protease) produced a family of peptides with some evidence of the glucan-binding domain but in far lower yield. The tertiary structure of the domain was critical to its resistance to proteolysis; heat denaturation of GTF-S before trypsin digestion resulted in cleavage of the enzyme to small limit peptides leaving no evidence of the glucan-binding domain. The amino acid composition of the peptide was very similar to that of the native enzyme. The common occurrence of proteases in oral streptococcus cultures and reports of glucosyltransferase degradation during purification and storage raises the possibility that some accounts of glucan-binding receptors are peptides derived from glucosyltransferase. Kinetic implications of a glucan-binding domain are discussed.

Amino Acids↗