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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 1,063 records · Page 59Linked to original sources

Different effects of dynorphin A on in vitro guinea pig hippocampal CA3 pyramidal cells with various degrees of paired-pulse facilitation.

We investigated the effects of dynorphin A (Dyn A), a heptadecapeptide, on the population spikes of the guinea pig hippocampal CA3 pyramidal neurons, in vitro, using paired-pulse stimulation of the mossy fibers. Dyn A produced facilitatory and inhibitory effects on the population spikes in the preparations with lower and higher degrees of paired-pulse facilitation, respectively. Morphine and D-Ala2, D-Leu5-en-kephalin, mu- and delta-agonist, respectively, predominantly potentiated the population spikes, while kappa-agonists such as U-50, 488H and bremazocine mainly caused an inhibition. These results suggest that Dyn A has two separate (excitatory and inhibitory) effects on the guinea pig hippocampal CA3 neurons through mu-(delta) and kappa-opioid receptors, respectively.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Seven cases of pelvic exenteration combined with sacral resection for locally recurrent rectal cancer.

Local recurrence of rectal cancer following abdominoperineal resection is rarely amenable to limited resection. Carcinoembryonic antigen assay is valuable for diagnosing most recurrent rectal cancers, but it is inadequate for early detection. Pelvic computed tomography examination is very valuable for the early detection and localization of recurrence in relation to pelvic structures and can also serve as a guide in percutaneous needle biopsy of the tumor. Seven patients with deeply invading recurrent lesions underwent pelvic exenteration combined with sacral resection. The ileal segment conduit was used for ureteral urinary diversion. The mean operation time and blood loss were 8.8 hours and 6,200 ml, respectively. No operative deaths were encountered. One patient is alive 22 months postoperatively with no evidence of disease, and another patient is alive 32 months postoperatively with pelvic wall recurrence. This procedure seems a reasonable treatment for palliation and full recovery in certain patients.

Adult↗

Low-molecular-weight proteinase inhibitor of human epidermis inhibiting papain and trypsin activity.

A low-molecular-weight proteinase inhibitor was isolated from human epidermal extracts by means of ultrafiltration, gel filtration and ion-exchange chromatography. On polyacrylamide gel electrophoresis (PAGE), the isolated fraction exhibited a single band of activity at pH 9.4, and inhibitory activity against papain and trypsin was detected in this band. Using sodium-dodecyl-sulphate PAGE, the molecular mass of the inhibitor was estimated to be 2,200 daltons.

Electrophoresis, Polyacrylamide Gel↗

A simple and rapid in vitro test for determining sensitivity of cancer cells to anticancer drugs.

For practical utilization of chemosensitivity tests of malignant cells to anticancer drugs in clinical studies, we developed a new method which is simple, rapid, and applicable to fresh human tumors. The principle of the method is to measure the content of ATP of living cells by chemoluminescence, after drug exposure. A straight linear relationship was observed between the number of viable cells and the light intensity. This method seems to be a good indicator for the selection of anticancer drugs in cancer chemotherapy.

Adenosine Triphosphate↗

Latero-lateral end anastomosis for right hemicolectomy using staplers.

In seven patients undergoing right hemicolectomy for benign or malignant diseases, latero-lateral end anastomoses were made using stapling devices, LS (linear stapler) and GIA (gastrointestinal anastomosis). As no complications directly related to the anastomosis occurred, we conclude that anastomosis using stapling devices for right hemicolectomy is a safe and rapid procedure.

Adult↗

Correlation of an in vitro chemosensitivity test using [3H] incorporation with the response in case of human tumor chemotherapy.

We developed a method for performing in vitro drug testing using [3H] incorporation into a primary human tumor. The test was applied to specimens from 60 patients with advanced malignancies, mainly gastrointestinal cancers. Forty-six specimens had sufficient growth for the drug testing. Forty-seven per cent of the gastric cancer specimens and 67 per cent of those from patients with colorectal cancer demonstrated an in vitro chemosensitivity. Among 9 chemotherapeutic drugs tested, ara-C, 5-fluorouracil, and mitomycin C showed the high percentages of positive sensitivity for gastric cancer, whereas actinomycin D, carboquone, and nimustine hydrochloride were sensitive in case of colorectal cancer. Clinical responses were compared with the results of the test. In 46 drug assays, in vitro/in vivo drug responses correlated in 78 per cent, with a true-positive rate of 47 per cent and a true-negative rate of 94 per cent. This test appears to be a reliable indicator for the clinical response to the same chemotherapeutic drugs in cases of the malignant diseases seen clinically.

Adult↗

Involvement of medullary opioid-peptidergic and spinal noradrenergic systems in the regulation of formalin-induced persistent pain.

To confirm that endogenous opioid-peptidergic systems and monoaminergic systems participate in the regulation of pain, the effects of a narcotic antagonist naloxone, inhibitors of enkephalin-degrading enzymes and monoaminergic blockers on persistent pain induced by formalin were investigated. Rats were given formalin into the plantar region of the left hind-paw and the duration of licking responses was measured at periods of 0-10 min (period I), 10-30 min (period II), 30-60 min (period III) and 60-120 min (period IV). Naloxone was administered systemically through mini-osmotic pumps and there was an enhanced licking response at period III and a tendency toward enhancement at period IV. The duration of the licking response at period III was increased when naloxone was given into the fourth ventricle in a dose of 30 nmol/rat, but not when it was injected into the lumbo-sacral subarachnoid space in doses of 30 and 300 nmol/rat. Thiorphan and bestatin injected simultaneously into the fourth ventricle (50 micrograms/rat) depressed the licking response at period III. Intrathecal injection of phentolamine significantly enhanced the licking response at periods I-III and produced a similar, but weaker effect at period IV. Intrathecal injection of propranolol and methysergide did not affect the response. These results suggest that opioid-peptidergic systems in the brain stem and noradrenergic systems in the spinal cord (via alpha-adrenoceptors) participate in the regulation of pain.

Animals↗

Inhibitory effects of the analgesic neuropeptides kyotorphin and neo-kyotorphin on enkephalin-degrading enzymes from monkey brain.

The inhibitory effects of the analgesic neuropeptides kyotorphin (Tyr-Arg) and neo-kyotorphin (Thr-Ser-Lys-Tyr-Arg) on enkephalin-degrading enzymes were studied. The enzyme used were aminopeptidase (AP), dipeptidyl aminopeptidase (DPP), enkephalinase-A (ENK-A), and angiotensin-converting enzyme (ACE), which were prepared from the monkey brain membrane fraction. Kyotorphin inhibited only DPP (IC50, 18 microM), and the mode of inhibition was non-competitive (Ki, 6 microM). Neo-kyotorphin inhibited AP, DPP, and ACE with IC50 values of 131, 306, and 200 microM, respectively, but the inhibition of the enzyme activities were not effective. The selective inhibition by kyotorphin suggested that kyotorphin might protect the released Met-enkephalin against enzymatic degradation by DPP. Thus, kyotorphin may not only induce the release of Met-enkephalin but also stabilize the released neuropeptide.

Aminopeptidases↗

[Prospective adjuvant chemotherapy, with mitomycin C plus long-term carmofur in colorectal cancer].

A prospective randomized controlled trial of adjuvant chemotherapy for colorectal cancer was performed in 41 institutions in the Tokai district. In the study, postoperative administration of Mitomycin C (MMC) followed by carmofur (HCFU) for more than three months (arm B) was compared to MMC alone (arm A). Of 173 patients subjected to curative resection (arm A = 80, arm B = 93) for colorectal cancer, 148 including 69 from arm A and 79 from arm B were evaluable. Before clinical evaluation of the effectiveness the background factors were analyzed by the chi square test and U-statics. There were no differences between them. At four years after surgery Kaplan-Meire's life table showed that the disease free survival of arm B was superior to that of arm A, but this difference was not statistically significant (generalized Wilcoxon test: P less than 0.10). However, the survival in arm B was significantly prolonged as compared with that in arm A (P less than 0.05). Side effects such as leukopenia and gastrointestinal distress caused by administration of MMC and pollakisuria and gastrointestinal distress caused by administration of HCFU were observed in approximately 35% of the patients. They were all slight or moderate and reversible.

Antineoplastic Agents↗

Radioimmunoscintigraphy of human gastric carcinoma xenografts with 125I-labeled monoclonal antibody.

A monoclonal antibody (GC 302) established in our laboratory, which was reactive with gastric carcinoma and other epithelial carcinoma but not with normal gastric mucosa or other malignant tumors of mesenchymal origin, was used to investigate the radioimmunolocalization of tumors. Various kinds of target cells (5 X 10(5)) were incubated with 125I-labeled GC 302, and radioactivity was determined with a gamma counter. It was shown that there was a 500- to 1,000-fold increase in counts for gastric carcinoma (NUGC-2, NUGC-4, MKN-28 and MKN-45) as compared to those of normal lymphocytes and about 100-fold increase as compared to melanoma or leukemia. These findings were consistent with those obtained from the study of immunohistochemistry using GC 302. An in vitro assay was also carried out using nude mice bearing gastric cancer and inoculated with 125I-labeled GC 302. There was a 2- to 3-fold increase in radioactivity in the tumor and a 4- to 5-fold increase as compared with the visceral organs. Although the tumor:blood ratio was relatively low, radioimmunoscintigraphy could be done successfully with the aid of computed radiography. We thus conclude that further testing of GC 302 is worthwhile to establish whether or not it is useful for radioimmunoscintigraphy of metastatic lesions of gastric cancer for possible clinical application.

Animals↗