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Biomedical subjects

K Koseki

Publications and source records attributed to K Koseki.

At least 37 records · Page 2Linked to original sources

[Clinical results of prophylactic intravesical chemotherapy on superficial bladder cancer using the dye exclusion assay].

A chemosensitivity test was carried out on superficial bladder cancer using the dye exclusion assay for the purpose of screening chemosensitive drugs for prophylactic intravesical chemotherapy. Bladder cancer cells of each patients were incubated, in vitro, in the presence of adriamycin, (2"R)-4'-0-tetrahydropyranyladriamycin, mitomycin C, pepleomycin and 4'-epi-adriamycin (500 micrograms/ml) at 5%, CO2, 37 degrees C for 2 hours. The cytotoxic effect of the drugs was evaluated by the ratio of stained cells by trypan-blue. The most effective drug was instilled postoperatively into the bladder 3 times for the first week, and every 2 weeks during the following 14 weeks. In 18 patients followed more than 4 months the prophylactic effect was evaluated. Fifteen of the 18 patients completed the protocol, but the remaining 3 patients failed to complete to the instillation because of severe irritability of the bladder. Tumor recurrence was demonstrated in two patients. Non-recurrence rates of tumors at 12 and 24 months were 93.8% and 82.0%, respectively. These results suggested that this rapid and handy assay was useful for the purpose of screening chemosensitive drugs for the intravesical chemotherapy.

Administration, Intravesical↗

A structural study of calcium-binding equine lysozyme by two-dimensional 1H-NMR.

Since 1H-NMR spectra of the calcium bound form (holo) and the calcium free form (apo) of equine lysozyme have an overall similarity, the folded structure of apo equine lysozyme seems to be similar to the holo structure at 25 degrees C and pH 7.0, even at low ionic strengths except for subtle conformational change. However, calcium titration experiments showed that a number of resonances change by a slow exchange process. The changes saturated at one calcium ion per one lysozyme molecule, and no more change was observed by further addition of calcium ions. This shows that just one calcium ion binds to equine lysozyme. To make assignments for these changed proton resonances, two-dimensional 1H-NMR studies, correlated spectroscopy (COSY), two-dimensional homonuclear Hartmann-Hahn spectroscopy (HOHAHA) and nuclear Overhauser effect spectroscopy (NOESY) were carried out. A structural model of equine lysozyme based on the crystal structure of human lysozyme was estimated and used to assign some resonances in the aromatic and beta-sheet regions. It was possible to use some proton signals as a probe to determine the specific conformational change induced by calcium ions. The calcium binding constant KCa was estimated from calcium titration experiments in which changes in the proton signal were monitored. The log KCa value was found to be on the order of 6-7, which is in agreement with the calcium binding constant determined by fluorescence probes. This means that the protons are affected by specific calcium binding.

Amino Acids↗

Kindling-induced changes of [3H]GTP binding in the cerebral cortical membrane.

Specific [3H]GTP binding to the cerebral cortical membrane was examined in amygdaloid kindled rats. Membrane fractions of the cerebral cortex obtained from kindled rats and sham operated control were incubated with [3H]GTP and the data were analyzed by Scatchard plots. There were no differences in the Bmax and Kd values in basal (without any agonists) binding between kindled and control membranes. In the presence of isoprenaline, beta-agonist, Bmax values increased in the control, but did not increase in the kindled group. The kindling-induced abolishment of isoprenaline effect on Bmax of GTP binding persisted at least two weeks. Specific GTP binding activity of control membrane increased in the presence of carbachol, muscarinic agonist. A carbachol-induced increase in specific GTP binding activity also disappeared in the kindled group. These results suggest that a functional imbalance among various types of GTP binding proteins (Gs, Gi or Go) might be related to the acquisition of the epileptogenesis in the kindling model of epilepsy.

Amygdala↗

[Chemosensitivity test on superficial urinary bladder cancer using the dye exclusion assay--model of intravesical chemotherapy].

A chemosensitivity test was carried out on superficial bladder cancers using the trypan blue dye exclusion assay for the purpose of screening chemosensitive drugs for intravesical chemotherapy. Transplantable murine bladder tumor cells (MBT-2) were incubated, in vitro, in the presence of adriamycin (4, 40, 400, 1000 micrograms/ml) as well as verapamil (3, 30, 100, 500 micrograms/ml) at 5% CO2, 37 degrees C for two hours. After cellular viabilities were calculated, MBT-2 cells were inoculated into the hind limbs of mice. The cellular viability was correlated well with the ratio of tumor appearance, tumor growth inhibition and prolongation of survival, and was dose dependent in the adriamycin treated groups. On the other hand, a reduction of cellular viability, tumor growth inhibition and prolongation of survival were seen in the high dose verapamil (100, 500 micrograms/ml) treated groups. Human superficial bladder cancer cells were incubated in the presence of adriamycin, 4'-0-tetrahydropyranyladriamycin, mitomycin C and pepleomycin (1000 micrograms/ml) and/or verapamil (500 micrograms/ml). The reduction rates of cellular viability markedly varied with the kind of anticancer drugs. A reduction of cellular viability of human tumor cells as well as MBT-2 cells was seen in the verapamil treated groups. This rapid and handy assay seems to be useful for the purpose of screening chemosensitive drugs for intravesical chemotherapy.

Administration, Intravesical↗

[Cytological changes in endocrine therapies of prostatic carcinoma].

We studied cytological changes by endocrine therapies of prostatic carcinoma in 31 cases. We originated a method of cytology, in which a prostatic fluid collecting catheter was used. This has been already reported in previous papers. By the therapies, carcinoma cells usually became edematous, swollen, squamous and finally keratinized and in the cytoplasm hematoxylin-stained granules often appeared. These findings were usually seen in two weeks after the onset of the endocrine therapy. But the degree of the changes differed among the cases and among the therapies. In some there was no response or only squamous metaplasia was found. Most of the carcinoma cells were viable. In these cases the therapies were thought to be ineffective and their mortality was high. On the contrary, in those with only keratinized cells, the therapies were thought to be effective and the mortality was low. We conclude that the cytological methods were useful for evaluating the therapies.

Aged↗

Structural specificity for biological activity of trichostatin A, a specific inhibitor of mammalian cell cycle with potent differentiation-inducing activity in Friend leukemia cells.

Biological activities of four chemically synthesized trichostatin-related compounds, (R)-trichostatin A, (S)-trichostatin A, (R)-trichostatic acid, and (S)-trichostatic acid, were investigated. Assays of differentiation-inducing activity in Friend leukemia cells and G2-arresting activity in the cell cycle of normal rat fibroblast cells were used as monitoring systems for comparing the bioactivities of these compounds. The results clearly showed that both of the enantiomers of trichostatic acid had no activity in both the assay systems. In the case of (S)-trichostatin A, the antipode of naturally occurring trichostatin A, 50% effective concentrations were determined to be 50-70-fold higher than those of (R)-trichostatin A. The relationship between this ratio and the value of enantiomeric excess strongly suggests that (S)-trichostatin A is also biologically inactive. These results indicate that the absolute configuration and the presence of the hydroxamate group of trichostatin A are essential for its biological activity.

Animals↗

[Selective conservatism in the management of abdominal stab wounds].

Two hundred and two consecutive patients with abdominal stab wounds in a 14-year period were analysed as follows: (1) The patients were classified into 4 categories; type I (no peritoneal penetration) 12%, type IIa (peritoneal penetration, no organ injury) plus type IIb (organ injury, no repair required) 26% and type III (organ injury, repair required) 62%. Injuries caused by kitchen-knife or violence, wounds in the lower chest or epigastrium, and harakiri-injuries (Japanese traditional method of suicide) resulted in high frequencies of type III injury. (2) Hematoemesis, hematuria, unstable hemodynamics, and signs of peritonitis were reliable indications for immediate laparotomy. Both stabography and diagnostic peritoneal lavage were unuseful as adjunctive diagnostic methods. (3) A policy of selective management in 126 patients (1981-1988), comparing with a policy of mandatory exploration in 76 patients (1975-1980), reduced unnecessary laparotomy rate from 32% to 14% (p less than 0.01). (4) Injury patterns, observed in this series and the reported series from Japanese emergency centers, were strikingly different from the American series. The author emphasize the threat of morbidity caused by delayed diagnosis in the application of selective conservatism and propose the acceptable rate of unnecessary laparotomy; less than 15%.

Abdominal Injuries↗

[A case of urachal abscess].

A 26-year-old male with urachal abscess was demonstrated. Ultrasonography, CT and MRI revealed that there was a mass at the supravesical region, which was connected to the umbilicus. However, a differential diagnosis as to whether the mass was a tumor or an abscess was difficult from these examinations. Thus we performed an open biopsy. A pathological examination revealed no malignant change in the biopsy specimen. On the other hand, the pathological diagnosis of a follicular tumor located at the roof of the urinary bladder was TCC G2, but we considered that, this change was a reactive hyperplasia with dysplasia resulting from chronic inflammation of urachal abscess. Thus, the complete excision of urachal abscess and partial cystectomy were performed. The serial sections of the bladder wall revealed no malignant changes. We reviewed similar cases reported in our country and discussed various factors causing urachal abscess, especially related to the infectious root.

Abscess↗

[A case of "interval" form of acute carbon monoxide poisoning--brain MRI and therapeutic effect of hyperbaric oxygenation].

A 43-year-old female who had suffered from paranoid reaction attempted suicide with city gas. She was admitted to an emergency hospital in a comatose state, regained consciousness the next day and was discharged 12 days after. However, on the 21st day after the poisoning, behavioral anomalies and staggering appeared. She was readmitted into another emergency hospital with the diagnosis of an "interval" form of acute carbon monoxide poisoning. She was performed hyperbaric oxygen therapy 42 times until the 53rd day after the accident. Nevertheless, her symptoms did not improve and remained in a state like an apallic syndrome. With little promise of improvement, she was moved to our hospital, and hyperbaric oxygen therapy further continued for 40 times which resulted in a remarkable recovery. Repeat EEGs were performed. On the 32nd day, EEG showed an abnormality consisting of generalized delta waves. On the 56th day, the abnormal EEG improved slightly with more alpha activity. EEG was normalized 126 days after. The X-ray CT scan on the 32nd day revealed low densities in the bilateral globus pallidus and the deep white matters adjacent to the frontal horns of the lateral ventricle and in the semioval centers. On the 57th day, these low density areas were depicted more clearly by the X-ray CT scan, which became less marked on the 73rd day. MRI was performed 3 times.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Clinical study on stab wounds of chest--factors that may influence their mortality].

Stab wounds of the chest occupy an important position in penetrating thoracic injuries in Japan. A retrospective review of 117 patients with stab wounds of the chest admitted to our hospital over the past 12 years (from 1975 to 1987) revealed some factors that might influence their mortality. Seven patients died from trans-diaphragmatic injuries of intra-abdominal organs. The management of intra-abdominal injuries was very important in thoracic stab wounds. Many of the patients with stab wounds of the precordial chest (danger zone) had cardiac or major vascular injuries, and the mortality rate of them was high. The mortality rate of the patients with stab wounds of the right lateral thorax was high, because many of them had trans-diaphragmatic liver injuries. We thought that right lateral thorax as well as precordial chest is the danger zone in thoracic stab wounds. Survival rate in the patients whose circulatory condition had been unstable when they admitted was very low. Five DOA (dead on arrival) patients with stab wounds of the chest required emergency room thoracotomy (ERT). One of them survived. Survival rate in the DOA patients with stab wounds of the chest was higher than that in the DOA patients with blunt thoracic injuries. ERT for cardiac insufficiency following stab wounds of the chest was thought an effective procedure for surviving. Survival rate of the patients with cardiac stab wounds was 63.6 per cent.

Adolescent↗

Mutual neoplastic promotion by instillation of mitomycin C and cauterization on rat bladder urothelium.

The authors studied the effect of bladder instillation of mitomycin C (MMC), a potential carcinogen, on the duration and severity of the hyperplasia induced by transurethral fulguration. This experimental system may simulate closely the intravesical chemoprophylaxis of MMC after transurethral resection of bladder cancer. Physiologic saline or MMC was instilled into the rat bladder once on the day of, or 3 or 7 days after cauterization. In all groups instilled with physiologic saline the changes were reversed by day 14. On the other hand, five of nine MMC-instilled rats developed papillary lesions, and three of these had mild dysplastic epithelium on day 84. Under the scanning electron microscope, the animals of these groups showed pleomorphic microvilli on the luminal surface of the regenerative cells on days 10 and 14 after cauterization. These results may indicate the mutual neoplastic promotion by instillation of MMC and cauterization to a certain extent.

Animals↗