Biomedical subjects

D S Hwang

Publications and source records attributed to D S Hwang.

51 records · Page 3Linked to original sources

PubMed1991

dnaK protein stimulates a mutant form of dnaA protein in Escherichia coli DNA replication.

Two proteins have been identified which stimulate a mutant form of dnaA protein in replication of plasmids containing the chromosomal origin, oriC. One of these is dnaK protein by the criteria of (i) absence of stimulatory activity in enzyme fractions from dnaK mutants, (ii) elevated levels of stimulatory activity in fractions from a dnaK protein overproducer, (iii) comigration of the stimulatory protein with authentic dnaK protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and (iv) replacement of this stimulatory protein by dnaK protein in stimulation assays. The stimulatory effect of dnaK protein on dnaA46 protein in replication suggests that this interaction, occurring prior to its action in DNA replication, may regulate its activity.

Bacterial Proteins↗

PubMed1990

Aggregated dnaA protein is dissociated and activated for DNA replication by phospholipase or dnaK protein.

dnaA protein isolated from Escherichia coli is equally distributed between a monomeric form, which is active for initiation of DNA replication, and an inactive, aggregated form which contains phospholipids. Replication activity of the aggregated form can be restored by treatments with either dnaK protein or phospholipase A2. Dissociation of the aggregate by dnaK protein is driven by ATP hydrolysis; action by phospholipase A2 requires a minute concentration of ATP only to stabilize the dissociated protein. Conversion of inactive dnaA-phospholipid complexes to the active form may contribute to the regulation of the initiation of chromosomal replication in E. coli.

Adenosine Triphosphate↗

PubMed1990

A novel protein binds a key origin sequence to block replication of an E. coli minichromosome.

A sequence of three tandem repeats of a 13-mer in the replication origin (oriC) of E. coli is the highly conserved site of opening of the duplex for initiation of DNA synthesis. A protein that binds this sequence has been discovered in E. coli and purified to homogeneity. This novel 33 kd polypeptide behaves as a dimer. Binding to the 13-mers is specific and limited to this region. At a ratio of 10-20 monomers per oriC plasmid, the binding blocks initiation by preventing the opening of the 13-mer region by dnaA protein. Once the 13-mers are opened by dnaA protein action, the 33 kd protein is without effect on the subsequent stages of replication. The specificity of binding and profound inhibitory effect suggest a regulatory role for this protein at an early stage of chromosome initiation.

Base Sequence↗

PubMed1990

Detection of prosthetic mitral valve leak: a comparative study using transesophageal echocardiography, transthoracic echocardiography, and auscultation.

Paravalvular leakage is a major complication of prosthetic valve dysfunction. Sixty-one subjects with valvular heart disease who had received prosthetic mitral valve replacement 5 months to 5 years before (43 received a porcine prosthesis and 18 received Bjork-Shiley valve prostheses) were evaluated for this complication. Careful auscultation was performed by two experienced cardiologists followed by transthoracic and transesophageal echocardiography. Physiologic leaks were detected in all Bjork-Shiley valves, but in only 30% of porcine valves using transesophageal echocardiography. These regurgitant jets were flame-like, with mean low velocities of 50 +/- 12.3 cm/sec and 48 +/- 18.2 cm/sec in the two types of valves. Neither transthoracic echocardiography nor auscultation could detect physiological regurgitant jets. Ten cases with paravalvular leak were detected by transesophageal echocardiography and subsequently demonstrated by left ventriculography (7 porcine, 3 Bjork-Shiley valves). Pathologic regurgitant jets were seen as high-velocity, systolic-retrograde turbulent flow across the prosthesis. However, only 6 cases of prosthetic valve dysfunction were detected by transthoracic echocardiography, 4 cases of mild paravalvular leakage went undetected. Thirteen of the 61 subjects had an apical systolic murmur and suspected prosthetic valve leakage; in 10 of the 13 cases the findings corresponded to those obtained by transesophageal echocardiography. In 3 cases of double valve replacement with Bjork-Shiley valves the magnitude of the leakage was overestimated by auscultation.

Adult↗

PubMed1990

Contributing factors to formation of left atrial spontaneous echo contrast in mitral valvular disease.

The formation of left atrial spontaneous echo contrast may relate to blood stasis. This study analyzed the factors contributing to the formation of that contrast. Transesophageal echocardiography, transthoracic echocardiography, cardiac catheterization, and left ventricular angiography were performed in 139 patients, divided into five groups. Predominant mitral stenosis with atrial fibrillation was found in 36 patients (group I); normal porcine valve in the mitral valvular area with atrial fibrillation in 31 (group II); predominant mitral stenosis with normal sinus rhythm in 26 (group III); moderate to severe mitral regurgitation with atrial fibrillation in 25 (group IV); atrial fibrillation with normal mitral valve in 21 (group V). The results showed left atrial spontaneous contrast echo was found in only 1 of 139 patients by transthoracic echocardiography and 62 of 139 cases were detected by transesophageal echocardiography. There was a high incidence of left atrial spontaneous echo contrast in cases of mitral obstruction with atrial fibrillation and enlarged left atrium (group I, 88%; group II, 74%), but a lower incidence in cases with normal sinus rhythm (group III, 4%), atrial fibrillation alone (group V, 16%), and increased left atrial flow velocity (group IV, 9.5%). The diameter of the left atrium was significantly different between presence and absence of left atrial spontaneous contrast echo (54.3 +/- 9.2 mm vs. 48.3 +/- 8.6 mm, p less than 0.01). The mean pressure gradient was similar in groups I and III (14.6 +/- 0.6 mHg and 14.4 +/- 2.8 mHg, respectively) but different in group II (10.9 +/- 3.2 mHg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

I-131-orthoiodohippurate renal function test in detection of renal artery occlusion in aortic dissection.

By use of I-131-orthoiodohippurate (I-131-OIH) comprehensive renal function test (CRFT), we studied 4 patients with aortic dissection and various degrees of renal artery obstruction and 39 patients without aortic dissection. Of the 39 patients, 3 had significant renal artery stenosis (RAS group) and 36 had normal renal arteriogram and renal function test (control group). Three of the 4 patients with aortic dissection had complicated renal artery occlusion (RAO group), one had independent RAS. The results indicate that: (1) In the RAO group, the difference in peak time (DPT) between the affected and contralateral kidneys was above 4 minutes: whereas that of the control group was 0-2 minutes (0.5 +/- 0.6 min). (2) In the RAO group, the percent difference of split effective renal plasma flow (%DSERPF) between the 2 kidneys were 29.6% and above or near 80% in patients with incomplete and complete RAO respectively; whereas that of the control group was below 22% (mean = 7.7 +/- 5.7%). In the RAS group, moreover, DPT was 0-2 minutes; and %DSERPF were above and below 22% in 1 case with marked (75% stenosis) and 2 with mild RAS (50-60% stenosis) respectively. The renogram curves were also evaluated. It was found that (1) In the RAO group, 2 cases with complete RAO showed flat shape in the affected kidney (similar to the background surve). The case with incomplete RAO showed markedly delayed rounding peak in phase 2 and slow descent in phase 3. The case with independent RAS showed only impaired phase 3 with saw-tooth waves and less steep slope. (2) In the RAS group, the 2 cases with mild RAS showed normal in one and slightly delayed peak with less steep descent in phase 3 in the other. The case with marked RAS showed reduced and delayed peak in phase 2, and less steep descent in phase 3 with saw-tooth waves and "cross-over" of the two kidney curves. It is concluded that use of I-131-OIH CRFT to evaluate DPT, %DSERPF and the renogram curve may help distinguish amongst RAO (with aortic dissection), RAS and the normal individual in most cases.

Adult↗

PubMed1989

Symptomatic relief of migraine: multicenter comparison of Cafergot P-B, Cafergot, and placebo.

A multicenter, randomized, double-blind trial was conducted to compare the efficacy of Cafergot P-B with that of its components, Cafergot, pentobarbital, and Bellafoline, and with placebo for the treatment of migraine. Patients with vascular headaches of the migraine type who regularly experienced nervous tension and some form of gastrointestinal distress with their headaches were randomized to one of five treatment groups. They were given treatment packets containing their assigned drug for use during two separate migraine attacks. Patients made pretreatment evaluations of the following symptoms: head pain, nervous tension, nausea, vomiting, anorexia, abdominal cramps, and photophobia. They made posttreatment evaluations of these symptoms 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ingesting their assigned drug. Improvement scores were calculated from the differences between the pretreatment and the posttreatment ratings. Patients also made a final global assessment of their drug's efficacy. All patients who took at least one dose of the study medication and completed a baseline evaluation and at least one postdose evaluation of severity of pain were included in the analysis (n = 254). The comparisons of particular interest were those between Cafergot P-B and Cafergot and between Cafergot P-B and placebo. Cafergot P-B was significantly more effective than Cafergot in relieving head pain at hours 2 and 3, nervous tension, nausea, vomiting, anorexia, and photophobia. Cafergot P-B was significantly more effective than placebo in relieving head pain, nervous tension, nausea (second headache only), vomiting, and photphobia. The incidence of reported adverse effects was no greater with Cafergot P-B than with Cafergot; however, patients given Cafergot P-B reported less vomiting than did patients given Cafergot. The results of this study show that addition of pentobarbital and Bellafoline to Cafergot provides greater relief of pain, vomiting, nervous tension, photophobia, and other symptoms associated with migraine, while reducing the severity of the nausea that may accompany a migraine headache or Cafergot therapy.

Adolescent↗

PubMed1989

The effect of intravenous captopril on the left ventricular function-an acute study by hemodynamics and radionuclide angiography.

Acute hemodynamic effects of intravenous captopril were measured, and left ventricular function was analyzed by radionuclide angiography in 11 patients with moderate to severe hypertension. All subjects received 1 mg captopril bolus injection initially, and followed in 10 minutes intervals by 2 mg or 5 mg injections according to their blood pressure response. Eight patients experienced an acute reduction of blood pressure; three patients remained unresponsive. The onset of action occurred within 5 minutes with peak effect at 5 to 10 minutes and a duration of action of 20 to 30 minutes. The hemodynamic effects were characterized by arteriolar dilation (reduced systemic vascular resistance P less than 0.01), and apparent venous dilatation (reduced right atrial, pulmonary wedge pressure P less than 0.05 & 0.01 respectively). Pulmonary vascular resistance was not altered. Ejection fraction remained unchanged. Isovolumic relaxation period lengthened (109 +/- 20.1 vs 137.39 +/- 21.15 msec, P less than 0.05) and coronary perfusion pressure gradients dropped (113.8 +/- 5.6 vs 101.1 +/- 11.3 mmHg P less than 0.001) following intravenously administered captopril. Intravenous captopril may reduce arterial pressure by inducing arterial dilatation with minimal adverse effect. The prolongation of isovolumic relaxation period should mainly attribute to the decrease of coronary filling load.

Captopril↗

PubMed1988

Purification and characterization of the dnaA46 gene product.

The alleles of dnaA46, dnaA5, and dnaA204 have been cloned from the Escherichia coli chromosome into a protein-overproducing vector. Under conditions of induced expression, similar amounts of dnaA46 and dnaA5 gene products and less of the dnaA204 gene product were observed. Facilitated by elevated expression levels, an improved method for purification of dnaA+ protein and the purification of dnaA46 protein have been obtained. The replication activity of dnaA46 protein did not appear to be thermolabile upon prior incubation at various temperatures. Thermolabile replication activity was observed under conditions of coupled DNA synthesis. In contrast with the wild type protein, DNA synthesis dependent on dnaA46 protein showed a pronounced lag before incorporation of deoxyribonucleotides.

Alleles↗

PubMed1988

Interaction of dnaA46 protein with a stimulatory protein in replication from the Escherichia coli chromosomal origin.

Highly purified preparations of dnaA46 protein have permitted its biochemical characterization in comparison with the activities of wild type dnaA protein. We have determined that dnaA46 protein was reduced in its ability to bind to DNA fragments containing oriC. This mutant protein was also defective in binding ATP and was inactive for replication of oriC-containing plasmids in purified enzyme systems. In contrast, dnaA46 protein was active for oriC plasmid replication when added to reactions containing a crude enzyme fraction deficient in dnaA protein. One or more proteins have been identified which appear to interact with dnaA46 protein prior to DNA synthesis. These studies suggest that this interaction is thermolabile. Stimulation of dnaA46 protein activity resulted in a reduction of the prolonged lag prior to DNA synthesis.

Amino Acid Sequence↗

PubMed1987

Fiorinal with Codeine in the management of tension headache: impact of placebo response.

The well-known difficulty in distinguishing the response to a combination headache medication and its individual components in the presence of a high placebo response was again demonstrated in a randomized, double-blind, placebo-controlled, multi-center trial comparing Fiorinal with Codeine and its Fiorinal and codeine phosphate components in relieving the pain, tension, and muscle contraction associated with tension headache. In the original analysis of the study data, no distinction was apparent between patient response to Fiorinal with Codeine and the response to the individual components, a finding that appeared to conflict with the results of a similar earlier study. This apparent discrepancy was attributable to a high placebo response in the later study. Separation of study subjects according to their baseline level of anxiety and pain identified a subset of less anxious patients with mild to moderate pain severity who were least likely to respond to placebo. Analysis of data from these patients showed that Fiorinal with Codeine was significantly better than placebo in improving patients' self-ratings of various symptoms of tension headache at 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. The combination drug was also consistently superior to Fiorinal alone and codeine alone in improving the patients' self-evaluation items, and differences between the combination and its components were generally of statistical or borderline significance during the last half of the study. The investigators' assessments of the effect of treatment on the three principal variables in tension headache (namely, headache pain, psychic tension, and muscle contraction of the head, neck, and shoulders) at the final patient visit also showed Fiorinal with Codeine to be not only significantly superior to placebo but also consistently superior to either component. The superiority of the combination over Fiorinal alone achieved borderline significance for headache pain and psychic tension.

Adult↗

PubMed1981

Further delineation of the C (trigonocephaly) syndrome.

This communication brings the number of recognized cases of the C (trigonocephaly) syndrome to 11. The pattern of findings includes an anomaly of the anterior cranium and frontal cortex (trigonocephaly), the root of the nose (broad nasal bridge, epicanthus, and short nose), and palate (thick anterior alveolar ridges); abnormalities of the limbs (polysyndactyly, bridged palmar creases, short limbs, and joint dislocations and/or contractures); visceral defects (congenital heart defects, cryptorchidism, and abnormal lobulations of the lungs and kidneys). Auricular, mandibular, skin, and genital abnormalities also occur. Consistent neurological findings are hypotonia, strabismus, and psychomotor retardation; seizures have been reported. Normal chromosomes, normal parents with multiple affected offspring, equal sex ratio of affected individuals, and consanguineous matings all support autosomal recessive inheritance of the C syndrome. In autopsied cases, there has been a suggestion of defective central nervous system myelination. About 1/2 of the case have died within the first year. All survivors have severe to profound mental retardation except for one child who has moderate retardation.

Abnormalities, Multiple↗

PubMed1972

Increased tolerance of leukemic mice to arabinosyl cytosine with schedule adjusted to circadian system.

Mice (BDF(1)) inoculated with L1210 leukemia survive for a statistically significantly longer span when four courses of arabinosyl cytosine are administered at 4-day intervals-not in courses consisting of eight equal doses at 3-hour intervals, but in sinusoidally increasing and decreasing 24-hour courses, the largest amount being given at previously mapped circadian and circannual times of peak host resistance to the drug. This finding relates to the many therapeutic situations involving rhythmic, and thus predictable, cycles in the host's tolerance of undesired effects from the agent used.

Animals↗

PubMedDate not supplied

E. coli minichromosome replication: regulation of initiation at oriC.

The initiation of Escherichia coli DNA replication is a highly regulated event with many parameters exerting positive and negative effects. The activity of the dnaA protein (the initiator protein) is profoundly influenced by the tight binding of the adenine nucleotides ATP and ADP. Further regulation of dnaA protein activity may occur through dnaA protein-cell membrane associations. A replicatively inactive form of dnaA protein is found aggregated with phospholipids; enzymatic treatment of the aggregates with phospholipase A2 or dnaK protein liberates dnaA protein with restored replication activity. Proper DNA structure is essential for replication. The energy stored in the DNA's supercoiling is crucial for dnaA protein's ability to initiate replication. Under conditions where strand-opening by dnaA protein is inhibited, such as low free superhelicity, an R-loop formed by RNA polymerase activates the origin at a distance by aiding strand-opening. A novel protein has been identified as a specific inhibitor of the initiation of DNA replication. This 33-kDa protein binds to the AT rich region of oriC and inhibits strand-opening by dnaA protein.

Bacterial Proteins↗

PubMedDate not supplied

Evaluation of two viral inactivation methods for the preparation of safer factor VIII and factor IX concentrates.

We report here the results of our evaluation of two procedures to eliminate viruses in factor VIII and factor IX coagulation factor concentrates. Both procedures were equally effective in the in vitro destruction of marker viruses. However, in a controlled infectivity test in chimpanzees, treatment at 60 degrees C for 20 hours inactivated greater than 500 and less than 10,000 chimpanzee infectious doses (CID) of hepatitis B virus, while treatment at 98 degrees C for 30 minutes inactivated less than 500 CID. Both methods were successful in preventing infection with an undetermined amount of an indeterminate non-A, non-B hepatitis agent. The 60 degrees C, 20-hour treatment method rendered 5.25 logs of the putative acquired immune deficiency syndrome virus, human T-cell lymphotrophic virus III/lymphadenopathy virus, added to factor VIII or factor IX concentrates, undetectable. Heat-treated factor VIII and factor IX complex concentrates prepared by these methods were tested against corresponding untreated control lots. There was no significant difference in the plasma recovery or plasma half-life of the factor (p greater than 0.05). The treated concentrates were equivalent to the control concentrates with respect to vital signs, clinical laboratory studies, and adverse reactions. The heat-treated concentrates appeared bioequivalent to the untreated concentrates with the additional benefit of inactivation of potentially present infectious viruses.

Animals↗