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Biomedical subjects

O Kobayashi

Publications and source records attributed to O Kobayashi.

At least 127 records · Page 7Linked to original sources

[A clinicopathological study on gestational trophoblastic disease comparing with high risk criteria and diagnostic score of choriocarcinoma].

In the past 15 years, 274 patients with the gestational trophoblastic disease have been treated at Chiba University and the diagnosis of 125 patients was confirmed pathologically. There were 55 cases (44%) in the high risk and 70 cases (56%) in the low risk group with the following criteria: (1) the urinary hCG titer was more than 100,000 IU/L; (2) the duration between antecedent pregnancy and the start of treatment was more than 1 year; (3) antecedent pregnancies were full-term or abnormal pregnancies except hydatidiform mole. These pathologically confirmed patients were evaluated with the choriocarcinoma diagnostic score. From this study, the following results were obtained: (1) The overall remission rates in high risk and low risk patients were 79.1%, 100%, respectively. (2) Out of 55 patients with high risk diagnosed pathologically, 49 (89.1%) patients had choriocarcinomas. On the other hand, 65 (92.9%) patients with low risk had invasive moles. (3) The discrepancies between the pathological and the clinical diagnosis chiefly depended on the inadequate evaluation of recurrent cases and the pretreatment urinary hCG. (4) Compared with our criteria, the choriocarcinoma diagnostic scoring system more closely corresponds to the pathological diagnosis but this system is more complex and inadequate than our criteria for older up patients that have not been adequately followed up.

Biomarkers, Tumor↗

[A case of chondrosarcoma arising from the left first rib].

A 46-year-old female was admitted to our hospital because of a left supraclavicular tumor. The chest CT scan and MR imaging revealed that the tumor arose from the left first rib and developed into the supraclavicular region. In this case, we tried to resect the tumor using the so-called "trap-door" thoracotomy. Although removal of subclavian vessels and brachial plexus from the tumor was easily performed, we could not enough treat the vertebral side of the first rib through this thoracotomy without the T1 nerves injury. In cases of superior sulcus tumors developing into the posterior chest wall, a posterior incision combined with an anterior one will be useful to remove these tumors safely.

Chondrosarcoma↗

[Extended radical mastectomy using preoperative local injection of activated carbon particle adsorbing aclarubicin (ACR-CH)].

ACR-CH was injected prior to surgery of breast cancer. Incidence of black staining of regional lymph nodes and concentration of ACR in the nodes were examined in order to evaluate the usefulness of preoperative local injection of ACR-CH. 1) In 13 cases of extended radical mastectomy, black staining was seen in nodes of all the regions. Especially, in parasternal, retromanubrial, anterior mediastinal and supraclavicular nodes, 46% or more of the nodes were stained and ACR concentration of 6-7 micrograms/g was obtained. 2) When incidence of black staining of the metastasis-free nodes was compared with that of the nodes with metastasis, it was 79% in the metastasis free nodes and 42% in the nodes with metastasis. The average ACR concentration was 54.16 +/- 123.16 in the stained nodes and 2.58 +/- 3.59 in unstained nodes, the former being significantly higher than the latter. 3) Majority of the stained nodes with metastasis had only very small metastatic foci and nodes with significant metastasis were only very rarely stained. 4) In conclusion, we believe that anticancer effect of ACR-CH can be expected to small metastatic foci in the parasternal lymph nodes and more distal nodes, dissection of which tends to be incomplete at extended radical mastectomy, as well as to free cancer cells in the lymph vessels.

Aclarubicin↗

Presynaptic effect of muscle relaxants on the release of 3H-norepinephrine controlled by endogenous acetylcholine in guinea pig atrium.

The influence of nondepolarizing muscle relaxants (MR) on the resting and electrically evoked release of tritiated norepinephrine (3H-NE) was investigated, in the absence and presence of 10(-4) mol/l cocaine, in the in vitro right atrium preparation of guinea pigs (g.p.) preloaded with 3H-NE. In the absence of MR both resting and stimulated 3H and 3H-NE release remained relatively constant throughout the experiment and the ratios of the evoked release of 3H during consecutive stimulation periods (i.e. S2/S1, S3/S2) were close to unity. None of the MR had any effect on resting 3H release. Atropine (3 x 10(-7) mol/l), gallamine (7 x 10(-5) mol/l), and pancuronium (2 x 10(-6) mol/l), but not d-tubocurarine (5 x 10(-6) mol/l) significantly increased stimulated release of 3H-NE. The effect of MR on resting or evoked release of 3H-NE was not influenced by 10(-4) mol/l cocaine. In the presence of atropine gallamine and pancuronium did not affect the release of 3H-NE. This finding indicates that the effect of MR was mediated via presynaptic muscarinic receptors. Muscle relaxants and atropine inhibited these receptors and removed the tonic inhibitory effect of acetylcholine (ACh) released from the parasympathetic nerve endings on the release of NE from the sympathetic nerve. This was substantiated by the finding that in the present of cholinesterase inhibition, when the effect of endogenous ACh was amplified and thereby the cholinergic tone was dominant, the total release of 3H-NE evoked by stimulation was much lower and muscle relaxants and atropine were much more effective to enhance 3H-NE release. Gallamine and pancuronium also increased the force of contraction of the electrically stimulated atria. These findings indicate that the acceleration of the heart rate observed with gallamine and pancuronium in anesthetized man is due to increased release from, and not the inhibition of reuptake of NE by the sympathetic nerve endings of the right atrium.

Acetylcholine↗

Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release.

In order to extend the characterization of muscarinic receptors at presynaptic sites their inhibitory effect on the stimulation-evoked release of [3H]noradrenaline and [3H]acetylcholine from different axon terminals was studied and the dissociation constants and potencies of different antagonists were estimated, in guinea-pig and rat. While oxotremorine reduced the release of [3H]acetylcholine and [3H]-noradrenaline in a concentration-dependent manner from different release sites (Auerbach plexus, noradrenergic neurons in the right atrium, cerebral cortex), McN-A 343, an M1 receptor agonist, enhanced their release evoked by field stimulation. When the inhibitory effect of oxotremorine on transmitter release was studied, pancuronium, pirenzepine and atropine were competitive antagonists of presynaptic muscarinic receptors located on the noradrenergic axon terminals of the atrium. While atropine and pirenzepine inhibited the muscarinic receptors of cholinergic axon terminals in the Auerbach plexus, pancuronium and gallamine had a very low affinity. Significant differences were found in the affinity constants of antagonists for muscarinic receptors located in the cholinergic axon terminals of Auerbach plexus and cerebral cortex, and noradrenergic axon terminals of the atrium. While atropine and pirenzepine exerted similar effects on these presynaptic sites, pancuronium, gallamine and (11-(2-[diethylamino)-methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6(1-pyrido(2,3-b)(1,4)-benzodiazepin-6-on) were much more effective on muscarinic receptors controlling acetylcholine release from the cerebral cortex and noradrenaline release from the heart. There was more than 100-fold (2.0 pA2 units) difference in affinities of these antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

[A case of pulmonary alveolar proteinosis associated with fibrotic changes and alveolitis].

A 62-year-old male, who had worked for 20 years as a farmer and who had been exposed to respirable agricultural chemicals apart from silica, was admitted in April, 1987, because of progressed exertional dyspnea. The chest X-ray film on admission showed irregularly-distributed infiltrative shadows in both lung fields. The chest CT also revealed irregular increase of densities in lung fields. Though the TBLB specimen from right B8 indicated only fibrotic changes, the tissues obtained by open lung biopsy from right S3 and S8 revealed PAS-positive proteinaceous deposits in the alveoli as well as alveolitis or fibrotic change of alveolar septum. Bronchoalveolar lavage fluid (BALF) contained phospholipids composed mainly of lecithin. According to these findings, the case was diagnosed as pulmonary alveolar proteinosis associated with alveolitis and patchy fibrotic changes. It is not completely clear whether fibrotic changes are induced by pulmonary alveolar proteinosis itself or fibrosis and proteinosis result coincidentally from direct response to fibrogenic agents. Inhaled agricultural chemicals may play a role for the pathogenesis of this case, for which further studies are required.

Biopsy↗

[Preoperative treatment of lymph node metastases of gastric cancer by local injection of 5-FU adsorbed on activated carbon--clinical study of 5-FU concentration in resected lymph nodes].

The concentration of 5-fluorouracil (5-FU) in blood and lymph node of 55 patients with gastric cancer who were endoscopically injected 250 mg of 5-FU alone or adsorbed on activated carbon into the gastric wall or 300 mg of 5-FU dry syrup orally before operation, were measured chronologically. The concentration of 5-FU in blood were similar in all cases but higher in lymph node in the group given adsorbed preparation than other cases. In the cases given adsorbed preparation, the lymph node concentration was remained high 7 days after injection, and in 37% cases more than the minimum inhibitory concentration of 5-FU remained. Therefore, for the purpose to elicit anticancer effect on micrometastasis in lymph nodes in the patients with gastric cancer, endoscopically preoperative injection of 5-FU adsorbed on activated carbon seemed to be useful.

Adsorption↗

[Preoperative treatment of lymph node metastasis in cases of gastric cancer by local injection of anticancer drugs--preliminary report].

For the purpose of producing an anticancer effect on the micrometastasis of the lymph nodes and free cancer cells in the lymphatic ducts in a gastric cancer, activated charcoal was endoscopically injected into the gastric wall preoperatively in 49 cases to adsorb anticancer drugs. The correlation between the histological degree of black staining of the dissected lymph nodes and the clinicopathological factors was studied. Among 2,426 dissected lymph nodes, the degree of black staining was found to amount to 49.9%. Among 201 metastatic lymph nodes, the degree of black staining was 24.9%. Thus, the possibility of an anticancer effect was realized in 25% of the metastatic lymph nodes. From a study of the clinicopathological findings, the degree of black staining was low in cases of advanced cancer. In a histological study, the degree of black staining was found to be higher in the undifferentiated types than in the differentiated types, suggesting that there is a difference in the function of the lymph-reticulo-endothelial system according to the histological type.

Antineoplastic Agents↗

Chemotherapy for gestational trophoblastic tumors.

Virtually 100% of patients with nonmetastatic and low-risk metastatic trophoblastic tumors are now curable by only conventional chemotherapeutic agents such as methotrexate, actinomycin D, or their combination with or without other agents. However, approximately 30% of high-risk patients with metastatic trophoblastic tumors are resistant to conventional chemotherapy. All of the high-risk patients resistant to chemotherapy are those with metastatic choriocarcinoma. Thus, the efficacy of multidrug chemotherapy and combination chemotherapy of cisplatin or VP16-213 with other agents is now being examined.

Antineoplastic Combined Chemotherapy Protocols↗

Direct evidence that pancuronium and gallamine enhance the release of norepinephrine from the atrial sympathetic nerve by inhibiting prejunctional muscarinic receptors.

The effect of different non-depolarizing muscle relaxants (gallamine, pancuronium, vecuronium, D-tubocurarine) on [3H]norepinephrine release in response to electrical stimulation was studied in isolated guinea-pig atrium. High pressure liquid chromatography combined with electrochemical and radiochemical detection revealed that the released radioactivity was mainly in the form of [3H]norepinephrine release. Oxotremorine, a pure muscarinic agonist, reduced the release of tritium. Gallamine and pancuronium, like atropine, prevented the inhibitory effect of oxotremorine. D-Tubocurarine and vecuronium had no such effect. These findings indicate that gallamine and pancuronium exert a presynaptic antimuscarinic, atropine-like effect, by inhibiting muscarinic receptors located on the axon terminals of sympathetic neurons thereby enhancing norepinephrine release. It is suggested that this phenomenon might play some role in tachycardia observed during surgical anaesthesia when gallamine or pancuronium have been administered.

Adrenergic Fibers↗

[Anticancer effect of VP16-213 (etoposide) on three choriocarcinoma cell lines].

A new anticancer drug, VP16-213 was studied in vitro to determine its effect upon 3H-thymidine uptake and the survival rate of choriocarcinoma cells in comparison with the effect of MTX and Act-D. Three human choriocarcinoma cell lines, BeWo, HCCM-5 and SCH were used. The results were as follows; Serum VP16-213 levels were 10.3 +/- 1.19 micrograms/ml and 1.35 +/- 0.38 micrograms/ml at one hour and 12 hours after the administration of 100mg of VP16-213, respectively. In those three cell lines, VP16-213 suppressed cellular 3H-thymidine uptake by 70% as compared with the control. On the sixth day after exposure to VP16-213, the survival rate of choriocarcinoma cells was less than 10% in each of the three cell lines. One of the most prominent pharmacodynamic characteristics of VP16-213 was a rapid influx and efflux mechanism as seen in MTX. From the above, the anticancer effect of VP16-213 upon those three cell lines was supposed to be equal to or more than those of MTX and Act-D.

Cell Line↗

[New combination chemotherapy against drug-resistant choriocarcinoma].

The remission rates of 373 patients with trophoblastic diseases were analysed according to the change in therapeutic methods. The following results were obtained. 1) In patients in the "low risk" and nonmetastatic "high risk" group, the remission rate was 100%. On the other hand, in those in the metastatic "high risk" group, the remission rate was only 71.4%, even if triple chemotherapy with methotrexate (MTX), actinomycin D (Act-D) and cyclophosphamide (CPM) was given primarily or secondarily. 2) Thirty-two of the patients in the metastatic "high risk" group underwent primary triple chemotherapy. Eleven additional patients in the same group who had never responded to initial chemotherapy of a different regimen had triple chemotherapy. The overall remission rates were 65.6% (21/32) and 45.5% (5/11), respectively. 3) The remission rate in those with recurrence who underwent triple chemotherapy was 44.4% (4/9). But two of these patients had a re-relapse. 4) Six of the patients in the metastatic "high risk" group had MEA protocol with a moderate dose of MTX, Act-D and etoposide. Five of them achieved remission. 5) The side effects of MEA protocol were not so serious, although alopecia and severe anemia were found in 100% and 75.8% of the patients, respectively.

Antineoplastic Combined Chemotherapy Protocols↗

[A study of lymph node metastasis in gastric cancer--a new method for fixing resected specimens with methylene blue formalin].

Lymph node metastasis in 171 cases after a radical resection of the gastric cancer have been studied by means of examining specimens of these lymph nodes fixed with methylene blue formalin. The number of the resected lymph nodes in a single case was 50.3 on the average. By the Appleby method this number was 82.8. The rate of metastasis (the number of cases with lymph node metastasis measured against the number of patients) was 43.9%. The frequency of metastasis (the number of metastasized nodes versus the number of dissected nodes) was 11.3%. When classified by location no difference was noted, but in the group which showed an infiltration of a macroscopic type or an undifferentiated adenocarcinoma, the rate of metastasis and the frequency of metastasis was found to be higher than in the group with a non-infiltration type or a well-differentiated adenocarcinoma. Although the metastatic rate of perigastric nodes (No. 1-6 was higher than in the other lymph node group (No. 7-11), no difference was recognized between both groups in the frequency of metastasis.

Formaldehyde↗

[Synergistic effect of amphotericin B and actinomycin-D against two human choriocarcinoma cell lines].

The sensitivity to actinomycin-D (Act-D) and the changes in survival rate of two human choriocarcinoma cell lines (BeWo and SCH) were studied in vitro and the following results were obtained. BeWo was shown to be more sensitive to Act-D than SCH, when the survival rate was compared in the two cell lines. 3H X Act-D uptake was 39 pmol/10(6) cells in BeWo and 12 pmol/10(6) cells in SCH after a two hours treatment. Those results suggested that the sensitivity to Act-D of choriocarcinoma cells was positively correlated with the intracellular Act-D concentration. The intracellular Act-D concentration was increased depending upon the concentrations of amphotericin B (AMB). After a two hours treatment with Act-D and AMB, the intracellular Act-D concentrations were twice in BeWo, and 2.3 times in SCH comparing with those treated with Act-D alone. The synergistic effects of Act-D and AMB on the survival rate were 1,000 times in BeWo and 100 times in SCH compared with those treated with Act-D alone. From the above, combination therapy with Act-D and AMB was supposed to be one of the trial methods in the treatment of drug resistant choriocarcinoma.

Amphotericin B↗

[Fundamental and clinical study of chemotherapy of refractory choriocarcinoma].

Since the introduction of MAC therapy in 1973, choriocarcinoma has become one of the most curable gynecologic malignancies. But in MAC resistant cases, the therapeutic results have been unsatisfactory. To establish the proper therapy for MAC resistant choriocarcinoma, fundamental experiments with MTX resistant HM cell lines were carried out with the aim of their clinical application. The effective combination in the treatment of choriocarcinoma appeared to be 10 to the minus 5th power mol of MTX and 10 to the minus 8th power mol of Act-D, considering its effect in cell proliferation inhibition, deoxyuridine uptake inhibition and dihydrofolate reductase activity suppression. Taking the effects of Oncovin confirmed by the experiments with nude mice into consideration, a combined moderate dose of MTX, Oncovin and Act-D, namely MOA therapy was used. The protocol of MOA therapy is as follows: The first day, MTX 150mg bolus, 300mg drip infusion for 4 hours, Oncovin 2mg bolus and Act-D 0.5mg bolus. From the second to the fifth day, Act-D bolus. MAC was effective in only one of the eight recurrent cases, but on the other hand, MOA was effective in five cases of choriocarcinoma including two MAC resistant cases. Therefore, MOA seemed to be a more effective therapy than MAC.

Adult↗

[Analysis of pregnancy outcome after chemotherapy of trophoblastic disease].

The pregnancy outcome of 57 women who had been treated for trophoblastic disease, between 1975 and 1982, was studied. All patients had regular menstrual cycle within six months after the last chemotherapy. Frequency of secondary infertility is 5% (3/60). No correlation between the amount of chemotherapy and secondary infertility was apparent. Of eighty-three pregnancies in 57 women, 55 pregnancies or 66.3% terminated in full term deliveries, 4 or 4.8% terminated in premature deliveries. Eleven of the 83 or 11.3% ended in spontaneous abortions and 2 or 2.4% in recurrent hydatiditorm mole. Only one infant (1.7%) had congenital malformation. There was no increase in fetal wastage or congenital anomaly when compared with pregnancies prior to chemotherapy or after untreated molar patients. Among the 59 live born infants, 4 or 6.8% infants belong to light for date, 49 or 83.1% to appropriate for date and 6 or 10.2% to heavy for date. Chemotherapic agents, mainly MTX and Act-D, appeared to have no effect on fetal growth. The incidence of choriocarcinoma subsequent to pregnancy in treated patients was 1.8% (1/57) and was 0.6% (2/365) in untreated molar patients (n.s.).

Abortion, Spontaneous↗