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Biomedical subjects

S C Cheng

Publications and source records attributed to S C Cheng.

At least 109 records · Page 6Linked to original sources
PubMed1985

Hereditary ovarian carcinoma. Biomarker studies.

Three ovarian-cancer-prone kindreds were studied, two of which contained identical twin sisters concordant for ovarian carcinoma. In one kindred, both identical twin sisters had daughters with ovarian carcinoma. In another kindred, one of the identical twin sisters had an ovarian-cancer-affected daughter. Ovarian carcinoma showed vertical transmission in all three families in a pattern consonant with an autosomal dominant mode of inheritance. Medical-genetic survey of each family included detailed questionnaires with retrieval of primary medical and pathology documents on cancer of all anatomic sites. Putative biomarker determinations included: (1) in vitro hyperdiploidy in dermal monolayer cultures; and (2) lower serum levels of alpha-L-fucosidase (less than or equal to 275 IU/ml) in all cancer-affected patients and statistically significant lower levels in 50% risk individuals when compared to spouse and published controls (P = 0.04 and P = 0.0002, respectively). These findings are discussed in context with the eventual development of a risk factor profile which, given acceptable sensitivity and specificity, would enable identification of individuals who would be prime candidates for intensive surveillance/management programs.

Adult↗
PubMed1985

Extent of equilibrium perturbation of the DNA helix upon enzymatic methylation of adenine residues.

The extent of equilibrium perturbation of the DNA helix associated with enzymatic methylation of dA residues has been determined by the agarose gel electrophoresis band-shift method. Utilization of EcoRI methylase under conditions of reduced specificity together with Escherichia coli dam methylase permitted modification of up to 300 dA residues/plasmid pBR322 dimer. A conformational change associated with methylation was observed, with the magnitude of the transition being linear with extent of modification of relaxed DNA circles. The conformational change corresponds to an unwinding of the DNA helix by 0.5 degrees/methyl group transferred to relaxed molecules. The magnitude of the effect was independent of temperature from 5-37 degrees C indicating that it is not the consequence of a thermal transition within this range.

Adenine↗
PubMed1985

Molecular consequences of specific intron mutations on yeast mRNA splicing in vivo and in vitro.

We have altered the TACTAAC sequence in the yeast CYH2m gene intron to TACTACC. This mutation changes the nucleotide at the normal position of the branch in intron RNA lariats produced during pre-mRNA splicing, and it prevents splicing in vivo. In a yeast pre-mRNA splicing system, CYH2m pre-mRNA carrying the TACTACC mutation is not specifically cut or rearranged in any way. Substitution of an A for the first G of the CYH2m intron, converting the highly conserved GTATGT 5' splice site sequence to ATATGT, also blocks intron excision in vivo and in vitro: pre-mRNA carrying this mutation was still cut normally at the mutant 5' splice site in vitro, to give authentic exon 1 and an intron-exon 2 lariat RNA with an A-A 2'-5' phosphodiester linkage at the branch point. This lariat RNA is a dead-end product. The subsequent cleavage at the 3' splice site is therefore sensitive to the sequence of the 5' end of the intron attached at the branch point.

Base Sequence↗
PubMed1985

Inducing anesthesia with a GABA analog, THIP.

The authors have postulated previously that general anesthetic agents act via a potentiation of the inhibitory action of gamma-aminobutyric acid (GABA) at central synapses. If the hypothesis is true, GABA should induce anesthesia, however, GABA itself does not pass through the blood-brain barrier. A GABA analog was sought as a substitute to test the authors' hypothesis. A new bicyclic GABA analog, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) was selected because its properties are similar to GABA in vitro. THIP was found to induce anesthesia in rodents, and its behavior was compared with that of thiopental, ketamine, midazolam, and gamma-hydroxybutyrate. Complete loss of righting reflex occurred with doses of THIP and thiopental just under 100 mumol/kg, with ketamine and midazolam less than 50 mumol/kg and with gamma-hydroxybutyrate of more than 6,000 mumol/kg. Complete recovery from thiopental and ketamine occurred in less than 5 min, with midazolam recovery required about half an hour and with gamma-hydroxybutyrate and THIP it took about 1 1/2 h. THIP induced analgesia as well as sedation and loss of righting reflex. Recovery was complete, and no adverse effects were noted in these rodents.

Analgesics↗
PubMed1985

Sign of complete sympathetic blockade: sweat test or sympathogalvanic response?

The sensitivity, specificity, and accuracy of the cobalt blue and ninhydrin sweat tests were compared with the sympathogalvanic response (SGR) in assessment of complete sympathetic blockade. Patients were randomly assigned to receive epidural administration of either preservative-free physiologic saline solution and 80 mg methylprednisolone (group I, control group, 9 patients) or 1.5% lidocaine with 80 mg methylprednisolone (group II, sympathetic blocked group, 10 patients). In group I, there was one false positive SGR (absence of SGR) before the block and there were four false positive SGRs after the block. In comparison, there were no false positive sweat tests (absence of sweating) before and after injection in group I. In group II, there were three false positive SGRs and no false positive sweat test before injection. After injection, one patient with an upper level of sensory blockade at T5 had persistent SGRs and positive sweat tests (false negative results). The study showed the sensitivity of the SGR and the sweat tests to be 90%. The specificity of the SGR was 56% compared to 100% for the sweat tests. The accuracy of the SGR was 74% compared to 95% for the sweat tests.

Adult↗
PubMed1984

Isolation of gram quantities of EcoRI restriction and modification enzymes from an overproducing strain.

Structural genes for EcoRI restriction endonuclease and modification methylase have been inserted into the plasmid vector pKC30 (Shimatake, H., and Rosenberg, M. (1981) Nature (Lond.) 292, 128-132) downstream from the bacteriophage lambda pL promoter. Upon induction of pL expression in strains producing a thermolabile lambda cI857 repressor, synthesis of EcoRI polypeptides is enhanced to the extent that after 4 h they represent several per cent of the total cell protein. Purification of activities overproduced in this manner yields preparations of endonuclease and methylase which appear identical to those obtained from conventional sources, with overall yields corresponding to 0.5 to 0.9 g of each enzyme/kg of cell paste.

DNA Restriction Enzymes↗
PubMed1984

Genetic predisposition to breast cancer.

Breast cancer risk factors are closely intertwined with the patient's cultural background, which may contribute to breast cancer aggregations within families. The difficult questions are: (1) does a truly hereditary breast cancer subset exist; (2) which familial aggregations are hereditary; and (3) is the hereditary form distinctive from its sporadic counterpart? These queries will be resolved once biomarkers are identified that show high sensitivity and specificity with genotype. The authors provide a review of this subject and will focus on their recent discovery of increased in vitro hyperdiploidy in cultured skin fibroblasts from patients with or at risk for hereditary breast cancer. The authors discuss findings from their study of family histories in 225 consecutively ascertained patients with verified breast cancer from the Creighton University School of Medicine Oncology Clinic. Findings consistent with an hereditary breast cancer syndrome were identified in 5% of the patients. Given the 112,000 new cases of breast cancer in the United States in 1982, the authors estimate that with a confidence coefficient of 0.95 between 2410 and 8790 of these individuals will manifest hereditary breast cancer. Specific surveillance/management programs should be geared to high-risk members of these families in which cancer yield will be predictable.

Adolescent↗
PubMed1984

Induced enzyme release from synaptosomes by halothane.

GABA-transaminase has been found to be released from rat brain synaptosomes by halothane in a dose-related manner. The releases of both GABA-transaminase and succinic semialdehyde dehydrogenase were increased with time. The release of other enzymes (creatine kinase, glutamate decarboxylase, aspartate transaminase, lactate dehydrogenase, and malate dehydrogenase) was less in magnitude and not related to the duration of incubation. Such observations suggested a specific event in the halothane-induced release of GABA-catabolizing enzymes. A suggestion linking mode of anesthetic action to a mitochondrial effect of volatile anesthetics was made.

4-Aminobutyrate Transaminase↗
PubMed1983

Positive-selection cloning vehicle useful for overproduction of hybrid proteins.

Plasmid pSCC31 contains the EcoRI endonuclease gene downstream from lambda pL. It does not yield transformants upon introduction into Escherichia coli unless the structural integrity of the endonuclease is destroyed. This makes it useful as a positive-selection cloning vehicle which can be employed for regulated overproduction of hybrid proteins.

Cloning, Molecular↗
PubMed1981

Inhibition of GABA metabolism in rat brain slices by halothane.

Based on studies with rat cerebral cortex slices, it was previously hypothesized that halothane anesthesia may result from increased GABA (gamma-aminobutyric acid) content in the synapses. Since GABA is an inhibitory neurotransmitter, such increases may cause a reduction in synaptic activity. The increase in GABA content could arise from several possible causes which are examined in this study using rat cerebral cortex slices as a model. The effects of halothane on uptake, release, and catabolism of GABA were determined. Uptake was studied by the amounts of radioactive GABA accumulated by the slices, and release studied by that discharged into the medium from slices preloaded with radioactive GABA. Catabolism was assessed by preloading the slices with radioactive GABA and then followed by measuring the amount of radioactivity found in unmetabolized GABA or in pooled GABA metabolites. Since CO2 was established as a major metabolite, it was subsequently used alone to measure the inhibition of GABA catabolism in the presence of varying amounts of halothane. Halothane (3 per cent) did not affect the high-affinity uptake or the release of GABA but did inhibit the catabolism of GABA. Using 14CO2 production as an index of catabolism, the inhibition of GABA catabolism by halothane was dose-related (8.79 per cent inhibition/per cent halothane). Such results support the hypothesis that halothane anesthesia may result at least in part from an inhibition of GABA catabolism which, in turn, causes increased GABA level in the synapse with resultant synaptic inhibition.

Animals↗
PubMed1981

Effects of anesthetic agents on synaptosomal GABA disposal.

In brain slices, halothane was shown to inhibit the metabolic breakdown of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter. This inhibition leads to increased brain GABA content, presumably in the synaptic areas, and to the postulation that halothane anesthesia may arise from an enhanced synaptic inhibition due to this elevated GABA. The ability of many neurotropic agents to inhibit GABA breakdown was studied by assessing synaptosomal "GABA disposal". GABA disposal by intact synaptosomes, which simulate miniature synapses, measures the conversion of [1-14C]GABA to 14CO2 and includes the processes of uptake, release, and catabolism of GABA. The most potent inhibitor is chloroform, followed by halothane, enflurane, ether, and thiopental. Pentobarbital, ethanol, paraldehyde, and ketamine are weak inhibitors. Phenobarbital, morphine, and phenytoin are not inhibitory at pharmacologic concentrations. As a whole, anesthetic agents show particular inhibitory action on this metabolic process in this model system where the ID10 values (i.e., concentration of a drug necessary to produce 10 per cent inhibition of GABA disposal) correlate well with known pharmacologic potencies, ED50 values, or MACs. These observations support the possibility that anesthesia may be related to an inhibition of GABA disposal.

Anesthetics↗
PubMed1981

Inhibition of GABA metabolism in rat brain synaptosomes by midazolam (RO-21-3981).

Benzodiazepines are known to potentiate GABA (gamma aminobutyric acid) action in the brain. The effects of midazolam, a water-soluble benzodiazepine, on GABA disposal (14CO2 from [1-14C]GABA) and on the individual processes of GABA uptake, GABA release, and GABA-transaminase in the rat brain synaptosomal model system were studied. A 10 per cent inhibition of action was defined as ID10. Midazolam inhibited overall GABA disposal at ID10 = 13 micro M. The ID10 values for the three contributing process in the overall GABA disposal process are 580 micro M for GABA-transaminase activity, 96 micro M for GABA release, and 13 micro M for GABA uptake. The value for GABA release is probably not valid since it fell outside of the linear part of the regression line which was used for calculation. Therefore, GABA uptake inhibition appears to be responsible for the overall inhibition of GABA disposal. This value is consistent with the proposed hypothesis that anesthesia involves excess GABA in the synaptic area.

4-Aminobutyrate Transaminase↗
PubMed1979

Antecedent renal disease and the outcome of pregnancy.

We assessed the effect of "healed" childhood renal disease on subsequent pregnancies by following-up a cohort of 224 children initially hospitalized with kidney disease. The pregnancy experience in this cohort was compared to two "control" cohorts comprising 81 female siblings and 191 age-matched female patients hospitalized contemporaneously for respiratory infection. The incidence of spontaneous abortion, stillbirth, and pregnancy-associated hypertension was not different among the cohorts; however, the incidence of infants with low birth weights was significantly greater in the renal and respiratory disease groups. Childhood kidney disease followed by impaired renal function (serum creatinine greater than 1.5 mg/dL) was associated with greater maternal and fetal morbidity. Kidney disease in childhood followed by apparent healing and no functional renal impairment does not have an adverse effect on maternal welfare, although the incidence of infants with low birth weight is apparently increased.

Abortion, Spontaneous↗