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Biomedical subjects

Y Kang

Publications and source records attributed to Y Kang.

At least 235 records · Page 13Linked to original sources

[Efficacy and adverse effects of beta-interferon in the treatment of malignant glioma].

Sixteen patients with malignant glioma were treated by the intravenous administration of beta-interferon together with chemoradiotherapy. Five of the cases were recurrent gliomas. Seven of the 11 fresh cases were treated with beta-interferon, more than two months after cessation of the radiotherapy. Of the 16 cases, 12 cases showed partial regression of tumors, or no regrowth of tumors on CT scan, 2 cases showed no improvement, and 2 cases were unevaluable due to the short follow-up periods. IFN-beta is often administered, in combination with antineoplastic agents and radiotherapy, to patients with malignant glioma. Some patients have shown sufficient suppression of the growth of the malignant glioma only through administration of IFN-beta 1 x 10(6) IU once or twice a week. Some patients, however, have developed severe bone marrow suppression due to the combination therapy of IFN-beta and antineoplastic agents. Therefore, the blood of patients should be tested twice a week, and the data should be analyzed within the same day to determine the subsequent treatment. IFN-beta administration should be stopped if the platelet count drops below 1.0 x 10(5)/mm3 or half of the initial figure, and the course of disease of the patient should be carefully observed.

Adult↗

Synthesis and biological evaluation of certain 3-beta-D-ribofuranosyl-1,2,4-triazolo[4,3-b)pyridazines related to formycin prepared via ring closure of pyridazine precursors.

All three amino-substituted 3-beta-D-ribofuranosyl-1,2,4-triazolo[4,3-b]pyridazines (5, 19, and 20) structurally related to formycin A were prepared and tested for their antitumor and antiviral activity in cell culture. Dehydrative coupling of 4-amino-5-chloro-3-hydrazinopyridazine (7) with 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonic acid (6) in the presence of DCC and subsequent thermal ring closure of the reaction product (8) provided 8-amino-7-chloro-3-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)- triazolo[4,3-b]pyridazine (9). Dehalogenation of 9, followed by debenzoylation, gave the formycin congener 8-amino-3-beta-D-ribofuranosyl-1,2,4- triazolo[4,3-b]pyridazine (5). Similar condensation of 5-amino-4-chloro-3-hydrazinopyridazine (13) with 6 and dehalogenation of the cyclized product (16), followed by debenzoylation, gave the isomeric 7-amino-3-beta-D-ribofuranosyl-1,2,4- triazolo[4,3-b]pyridazine (19). DCC-mediated coupling of 6 with 6-chloro-3-hydrazinopyridazine (12), followed by ammonolysis of the cyclized product (21) with liquid NH3, provided a convenient route to 6-amino-3-beta-D-ribofuranosyl-1,2,4-triazolo[4,3-b]pyridazine (20). The structural assignment of 5 was made by single-crystal X-ray diffraction analysis. Compounds 5, 19, 20, and certain deprotected nucleoside intermediates were evaluated against L1210, WI-L2, and CCRF-CEM tumor cell lines, as well as against DNA and RNA viruses in culture. These compounds did not exhibit any significant antitumor or antiviral activity in vitro.

Animals↗

Intraoperative coagulation changes in children undergoing liver transplantation.

Intraoperative changes in blood coagulation were observed in eight children undergoing liver transplantation using a simplified coagulation profile (prothrombin time [PT], activated partial thromboplastin time [aPTT], and platelet count) and thrombelastography. Preoperatively, PT and aPTT were moderately prolonged (1.5 times control), and platelet count was greater than 100,000/mm3 in all patients but one (91,000/mm3). During the preanhepatic and anhepatic stages, PT, aPTT, reaction time, and coagulation time improved toward normal values, but platelet count and maximum amplitude did not change. Significant changes in coagulation occurred on reperfusion of the grafted liver: PT, aPTT, reaction time, and coagulation time were prolonged, and platelet count, maximum amplitude, and clot formation rate decreased. A heparin effect, which did not require treatment, was seen on reperfusion in four patients. Fibrinolysis occurred during the operation in five patients and was treated with Epsilon-aminocaproic acid (EACA) in one. Blood coagulation improved slowly, and values were close to baseline 90 min after reperfusion. In general, the coagulation changes seen in these children are similar to those in adults but less severe, possibly because of the preponderance of cholestatic disease in children compared with the more common hepatocellular disease in adults.

Aminocaproic Acid↗

Cloning and sequencing of a complementary deoxyribonucleic acid coding for a bovine alpha s1-casein A from mammary tissue of a homozygous B variant cow.

A cDNA clone for bovine alpha s1-casein variant A was isolated from a mammary gland cDNA library using a synthetic degenerate oligonucleotide probe. The largest Pst I insert containing an EcoR I site was sequenced. It contained 1090 base pairs, 47 in the 5' noncoding region, 603 in the coding region and 440 in the 3' noncoding region. The nucleotide sequence was compared with three published cDNA sequences for alpha s1-casein variant B. The most obvious difference was the absence of the 39 bases encoding the 13 amino acids that are present in the B variant but absent from the A variant. In addition, five other single base positions differed within individual codons among the four sequences at the third base for each codon, but this did not change the amino acids encoded. There were, however, a number of differences found in the 3' noncoding region. The isolated cDNA was subjected to site-directed mutagenesis to replace a Val-Ile dipeptide with Phe-Phe to increase the chymosin sensitivity of the protein. When the milk proteins from mammary gland tissue extracts were typed, the alpha s1-casein A gene product was not detected.

Amino Acid Sequence↗

An efficient and site-specific gene trimming method.

Trimming a DNA strand into a precisely determined fragment can be carried out efficiently by an improved method involving a site-specific trim-primer and a single-stranded DNA template which is generated from a multifunctional vector, pTZ18R, and linearized by using an Eco RI-pTZ18R splinter. A complementary DNA strand is synthesized by DNA polymerase I (Klenow), and the 3'-end of the template upstream from the annealed primer is trimmed by subsequent T4 DNA polymerase reaction. An ATG translation initiator codon or a termination codon can be incorporated into the trim-primer, providing versatility to this single-stranded DNA-initiated gene trimming method that can be applied to subcloning and expression of any DNA fragment with known terminal sequences.

Biotechnology↗

[Partially thrombosed radiculomeningeal arterio-venous fistula in spinomedullary junction].

A 58-year-old man was admitted to our hospital because of tetraparesis of fairly sudden onset. He had had difficulty in miction since 6 months earlier. MRI study showed a high intensity area in front of the medulla and a low intensity "vessel-like" shadow in front of the upper cervical region on T1-weighted image. The dorsal part of the medulla and cervical spinal cord showed diffuse low intensity signals in T1-weighted image. The intra-axial lesion appeared as high intensity signals in T2-weighted image. Angiography revealed a huge dilated vascular malformation fed by a third part of the right vertebral artery. The lesion in front of the medulla was not opacified. His neurological status progressively deteriorated, resulting in combined respiratory distress. Emergency surgery was performed only for posterior decompression. Although postoperative balloon catheterization was scheduled, he died of gastric perforation and pancreas necrosis one month after the operation. At the autopsy, it was found that the feeding artery of the AVM was branched from the junction of V3 and V4 of the right vertebral artery, where the artery penetrates the dura mater. The meningeal artery was engorged, and the radicular vein of C1 was markedly dilated due to the retrograde filling. The premedullary vessel was thrombosed, but the cervical part of the AVM showed eccentric hypertrophy of the wall and a partially organized thrombus. Intra-axially, the posterior funiculus was markedly destroyed and the spinal cord was edematous and subnecrotic.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Angiography↗

Excitatory synaptic actions between pairs of neighboring pyramidal tract cells in the motor cortex.

1. By spike-triggered averaging, we documented recurrent individual excitatory postsynaptic potentials (EPSPs) produced in 33 pyramidal tract (PT) cells (target) by the activity of axon collaterals of neighboring single PT cells (reference) in the motor cortex of the cat. 2. The computer was triggered by the spontaneous activity of reference PT cells or by current pulses applied to reference PT cells through the extracellular recording electrode. 3. The threshold for direct activation of PT cells was less than 0.1 microA with an anodal current pulse and 0.2-0.3 microA with a cathodal current pulse. 4. Application of an anodal current pulse directly activated only a single reference PT cell, the surface membrane of which was presumably touched by and sucked with the extracellular recording electrode. 5. When a cathodal current pulse was used, simultaneous activation of neurons or axons other than the reference PT cell was checked by changing the stimulus parameters along the characteristic strength-duration curve for the reference PT cell and/or by comparing averaged EPSPs obtained by cathodal stimulation with those obtained from spontaneous spikes of the reference PT cell. 6. Recurrent individual EPSPs were produced in fast PT cells by activation of neighboring slow PT cells and also of neighboring fast PT cells. Some recurrent individual EPSPs were also observed in slow PT cells. 7. The mean latencies of recurrent individual EPSPs produced by the spontaneous activity of reference slow and fast PT cells were 1.61 (n = 12) and 1.12 ms (n = 8), respectively. Their amplitudes ranged between 30 and 390 microV (n = 33). The rise time observed in fast PT cells with activation of slow and fast PT cells ranged from 1.6 to 3.6 ms (n = 20) and from 0.8 to 1.9 ms (n = 10), respectively. 8. The average conduction velocity of axon collaterals of slow and fast PT cells was estimated to be as slow as that of unmyelinated fibers in the cat. 9. It is suggested that axon collaterals of slow PT cells synapse onto more distal dendrites of fast PT cells than axon collaterals of fast PT cells.

Action Potentials↗

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats.

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.

Animals↗

[Treatment of vasospasm after ruptured cerebral aneurysms by 'pellet-cisternal-drain: PCD' containing sustained-release vasodilators].

Diltiazem or papaverine hydrochloride as vasodilators were polymerized with silicon polymer (MDX-4-4210: Dow Co.). The silicon pellets containing the drugs were placed in cisternal drainage tubes made of silicon, and used for the continuous cisternal drainage after the operations of ruptured cerebral aneurysms. This system was tentatively termed 'pellet-cisternal-drain; PCD'. The rate of diffusion of the drug from the pellets was examined in 30 patients who underwent surgery for ruptured cerebral aneurysms in the acute phase on the 0-4th postical days. 73.3% of patients had severe subarachnoid hemorrhage as group 3-4 in Fisher's classification in CT scan. The concentration of either drug in the cerebrospinal fluid on the 2nd to 3rd postoperative days reached the level of the maximum concentration obtained after bolus injection, and the level on the 5th to 10th postoperative days was similar to that observed several hours after bolus injection. The data showed that the sustained release pellet can act as a vasodilator, and its effects on cerebral vessels after an episode of subarachnoid hemorrhage continue for 2 to 3 weeks. All patients except one showed excellent results and returned to normal life.

Adult↗

Experimental induction of cerebral aneurysms in monkeys.

Saccular cerebral aneurysms were successfully induced in two monkeys treated with ligation of the common carotid artery, experimental hypertension, and beta-aminopropionitrile feeding. The cerebral aneurysms developed on the large arteries at the base of the brain, such as the anterior communicating artery and the internal carotid artery at the origin of the posterior communicating artery. Because of the similarity of the monkey to man as a species, the present results strongly suggest the significance of postnatal aggravating factors in the development of cerebral aneurysms in man.

Aminopropionitrile↗

Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation.

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗