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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 307 records · Page 17Linked to original sources

Radioimmunoassay for human pancreatic ribonuclease and measurement of serum immunoreactive pancreatic ribonuclease in patients with malignant tumors.

A method for radioimmunoassay of human pancreatic RNase was developed. The method is sensitive, reproducible, and specific. Almost no cross-reactivity exists between human pancreatic and liver RNases. A good correlation was observed between the serum concentration of pancreatic RNase as measured by radioimmunoassay and its enzymatic activity using polycytidylic acid as substrate. The concentration of serum pancreatic RNase correlates well with age, blood urea nitrogen, and albumin contents but does not correlate with serum amylase activity. Using the data of 52 patients with malignant tumors except pancreatic cancer, serum RNase level could be expressed by a multiple regression equation: Immunoreactive RNase content in pancreatic cancer was elevated in patients with complications from renal failure. Serum pancreatic RNase contents in patients with pancreatic cancer measured by radioimmunoassay agreed well with the values calculated using the equation derived from the data of patients with other malignant tumors.

Humans↗

Radioimmunoassays for two types of human urinary ribonucleases: differential determination of ribonucleases in human serum.

We developed radioimmunoassays for two types of human urinary ribonucleases. The assays are sensitive, reproducible and specific. One human urinary ribonuclease (RNase UL) showed strong immunological identity with human pancreatic ribonuclease, and the other ribonuclease (RNase Us) showed strong immuno cross-reactivity with human liver ribonuclease. There was no immuno cross-reactivity between these two urinary ribonucleases. Serum immunoreactive RNase UL was eluted as four peaks on phosphocellulose chromatography, whereas immunoreactive RNase US was eluted as a single peak. Serum content of immunoreactive RNase UL was 354 +/- 105 ng/ml (mean +/- SD) in normal individuals, and that of immunoreactive RNase Us was 15.9 +/- 5.7 ng/ml (mean +/- SD). No correlation was demonstrated between these two ribonuclease contents in serum.

Adult↗

[Chemotherapy of unresectable Borrmann's type IV stomach cancer].

In the inoperable Borrmann type 4 Gastric cancer, which is to be used as a synonym of gastric scirrhus clinically, it is regrettable but effect is hardly expected from radiotherapy or immunotherapy, and the treatment relies entirely on chemotherapy. We have reported the results of our questionnaires collected from 108 hospitals (internal medicine-40 and surgical-68) all over Japan to investigate the prevailing circumstances of inoperable Borrmann type 4 gastric cancer. Therapies performed by singular medication were: 1). oral and intravenous 5-FU-33.3%, 2). oral, intravenous and suppository tegafur-27.4% and intravenous MMC-27.4%, of the total 84 methods reported in the field of internal medicine; and 1). administration of 5-FU-29.1%, 2). intravenous MMC-26.8% and 3). tegafur-22%, of the total 127 therapies reported in the surgical field. The therapies performed by combined medications were: 1). 5-FU+MMC-22.6%, 2). MFC-12.1%, 3). tegafur+MMC, and FAM-8.3% (further 29 examples of combination medications consisting of 2-4 preparations), of the total 124 therapies reported in the field of internal medicine; and 1). 5-FU+MMC-22.6%, 2). MFC-12.1% and tegafur+MMC-7.3% (further 37 examples consisting of 2-4 preparations), of the total 124 therapies reported in the surgical field. The total cases judged as 'effective' in all the hospitals were 71. The breakdown is as follows: 1). 'effective for the primary focus'-47 cases/66.7%, expansion of affected site proved by gastric radiogram and endoscopic image-33 cases/46.5%, expansion of affected site proved only by endoscopy-4 cases/5.6%; shrinkage of malignant ulcer and flattening of randwall, disappearance of extra-gastric compression by endoscopic image-2 cases. 2). ineffective for the primary focus'-24 cases/33.8%, of which disappearance of or decrease in ascites-11 cases/15.5%; improvement of anorexia, nausea, vomiting, abdominal fullness, strange epigastric sensation, abnormal evacuation, disappearance of diarrhea etc. and increase in body weight-13 cases. In 50% survival period, the cases in which chemotherapy was judged as entirely ineffective were 283 and the period was 2.9 months. The 50i% survival period for the above-mentioned total effective cases was 8.5 months, of which the 50%r survival period for the effective cases by radiographic and endoscopic findings in the primary focus was 10.65 months showing the prolongation effect of life span. One year survival rate was also 36%. Draft of the Critria of Cancer Chemotherapy for Gastric Cancer proposed by Japanese Research Society for Gastric Cancer, which including the evaluation of Borrmann type 4 cancer, was introduced.

Antineoplastic Combined Chemotherapy Protocols↗

[Experimental study on abdominal arterial infusion of anti-cancer agents].

The distribution of Adriamycin (ADM), Mitomycin C (MMC) and 7-N-(p-Hydroxyphenyl)-Mitomycin C (KW 2083) in various organs inclusiding plasma level after intraarterial or intravenous infusion was determined in mongrel dogs and experimental dogs. Similar plasma time-course of ADM was obtained with both routes, showing the maximum level at 5 minutes after infusion. The maximum level with intravenous infusion was twice as highs as that with intraarterial administration. High levels of ADM were encountered in the liver, gallbladder and kidney after proper hepatic arterial infusion, in the angular region of the stomach after left gastric arterial infusion and in the gastric antrum after right gastroepiploic arterial infusion (0.8 mg/kg). There was no significant difference in plasma levels of MMC (0.2 mg/kg) and KW 2083 (1.0 mg/kg) between intraarterial and intravenous infusion. It was of interest that MMC was hardly measurable in the liver after proper hepatic arterial infusion of 0.4 mg/kg. On the other hand, rather high level of KW 2083 was observed in the liver, gallbladder and pancreas after proper hepatic arterial infusion of 1.0 mg/kg. Hepatic necrosis around the central hepatic vein noted at the histological examination seems to be due to infusion of above-mentioned anticancer agents. It is worth mentioning that the concentration of KW 2083 in tumor tissue of the stomach of experimental dog after right gastroepiploic arterial infusion was twice as high as that in intact gastric wall. Grade IIA histological alterations of tumor cells by Oboshi and Shimosato's Classification such as vacuolation of cytoplasm and pyknosis of nuclei were noted after KW 2083 infusion.

Abdomen↗

Purification, characterization and development of radioimmunoassay of human liver ribonuclease.

Human liver ribonuclease (RNase) was purified 36000-fold into an electrophoretically homogeneous state by column chromatography on phosphocellulose, gel filtration, poly(G) affinity chromatography, and heparin affinity chromatography. The molecular weight of the RNase estimated by SDS disc electrophoresis was 19,500. RNase was a heat- and pH-stable protein, and optimum activity was obtained at pH 7.0. The radioimmunoassay (RIA) for human liver RNase has been developed and the assay was shown to be sensitive (20 ng/ml), reproducible and specific. A good parallel relationship was observed between the standard curve and the dilution curves for serum and urine. No cross-activity was demonstrated between human liver and pancreatic RNase (less than 1%). In 44 normal subjects, the mean serum concentration of liver RNase determined by the RIA was found to be 99.4 ng/ml (SD +/- 66.3).

Adult↗

Retrovirus-related sequences in human DNA: detection and cloning of sequences which hybridize with the long terminal repeat of baboon endogenous virus.

Human DNA sequences which hybridized with the long terminal repeats (LTR) of baboon type C virus M7 were detected by non-stringent blot hybridization. About 7 to 10 discrete bands of the LTR-related sequences were commonly observed in the DNAs from four independent human cell lines after digestion with either Eco RI, Hind III or Bam HI. The amounts of these sequences were more abundant in tumor cell lines than in a non-malignant cell line. The human sequences related to the M7 LTR seemed to be located at relatively specific sites on the cell DNA. The human DNA clones which hybridized with M7 LTR were detected in the human DNA library described by Lawn et al. (Cell 15, 1157-1174, 1978), at a frequency of about 300 per haploid genome. Five clones were isolated which shared different extent of homology with M7 LTR and whose restriction maps were totally different one another. The DNA structures of two of them resembled the genome of retroviruses. These results suggest the presence of various types of the LTR-related sequences in human DNA: some of them might represent endogenous virus genomes of human cells.

Animals↗

A study on the pharmacological and biochemical profile of clocapramine.

Clocapramine was introduced into clinical use as a successor to carpipramine which is designated as a "désinhibiteur' by Deniker et al. Pharmacological and biochemical studies were carried out in order to elucidate the central action of clocapramine. Antidopaminergic activity of clocapramine was more potent than that of carpipramine. Clocapramine did not show any imipramine-like action; on the other hand, carpipramine partially did. We discuss the correlation between the preclinical findings so far obtained and clinical disinhibitory activity.

Animals↗

[Distribution of cefotiam dihydrochloride to the intraabdominal exudate (author's transl)].

The concentration of serum and intraperitoneal exudate after dripping intravenous administration of CTM were measured. Four male cases of the emergent laparotomy, a Cushing's ulcer, a hemorrhagic gastric ulcer, an adhesive ileus and acute terminal ileitis were investigated on this study. Two grams of CTM dissolving into 100 ml of physiological saline solution were prepared and administered in a period of 1 hour by intravenous drip (i.v.d.) for all cases after operation. The measurement of CTM-concentration in serum and intraperitoneal exudate were made at 30 minutes, 60 minutes following administration by serum and intraperitoneal exudate were made at 30 minutes, 60 minutes following administration by i.v.d. and at 30 minutes, hourly intervals over a 6-hour period after total administration. The intraperitoneal exudate for this study were collected through a drain which provided at the operation. These samples were measured by Agar-well method at Takeda Central Research Laboratory. Takeda Co., Ltd. The mean value of serum CTM at 30 minutes after the beginning of i.v.d. administration was 65.7 micrograms/ml and the maximum value, 79 micrograms/ml was obtained at 60 minutes. The following mean values at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours and 6 hours after total administration were 39.1, 26.4, 14.6, 8.9, 4.7 and 0.6 microgram/ml. On the other hand, the mean values of CTM intraperitineal exudate at the same time intervals were 4.9, 20.7, 32.0, 34.3, 22.4, 13.9, 11.2, 8.7 and 3.3 micrograms/ml. These results showed that there were much transfer of CTM between serum and intraperitoneal exudate corresponding to the amount of administration.

Adult↗

Purification and immunological characterization of human pancreatic ribonuclease.

Three alkaline RNases were purified from human pancreatic juice to near homogeneity as judged by sodium dodecyl sulfate and native polyacrylamide gel electrophoreses. The molecular weights of these RNases determined by sodium dodecyl sulfate electrophoresis were 27,000, 19,000, and 13,000. The activities of these three RNases were increased by addition of Mg2+, Ca2+, Co2+, K+, Na+, spermine, and spermidine and decreased by the addition of heparin, Cu2+, and Zn2+. These RNases showed higher hydrolytic activity toward polycytidylic acid than toward polyguanylic acid, polyuridylic acid, or polyadenylic acid. The three human pancreatic RNases were immunologically identical but differed from human liver RNase, as shown by Ouchterlony double-diffusion test. Radioimmunoassay of human pancreatic RNase showed that immunologically similar RNases are present in human saliva, and serum.

Animals↗

Experimental colonic cancer in a dog.

Experimental colonic carcinoma in a dog was induced by anal insertion of an N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) suppository (each cone containing 50 mg of ENNG) for 17 months. The dog was autopsied 20 months after the initiation insertion of the suppository. Grossly, the colonic wall from the anus of the 10-cm oral side of the colon was thickened, and there was an infiltrating tumor with shallow depressions in the rough mucosa. The lymph node around this portion were enlarged, and white spots were found in the liver and redness in the lungs. Histological examination of the colon revealed a variety of pathologic features, e.g., undifferentiated carcinoma, squamous cell carcinoma and malignant melanoma in the region adjacent to the anus. Well and moderately differentiated adenocarcinomas involving the proper muscle layer were found in a region oral to these tumors and were accompanied by marked invasion of the blood vessels and lymphatic permeation. There were metastases to the liver, lungs and lymph nodes which corresponded to the gross findings, and also metastases to renal glomeruli. A well differentiated adenocarcinoma and signet ring cell carcinoma were evident in the gastric mucosa. This experimental model should be useful for studies related to colonic carcinoma in humans.

Adenocarcinoma↗

Clinical evaluation of GABA in the treatment of cerebrovascular disorders. Multi-center double-blind study in comparison with pyrithioxine and placebo.

The therapeutic efficacy of GABA was compared with pyrithioxine and placebo in 432 patients with cerebrovascular disorders by a multi-center (50 hospitals) double-blind clinical trial. 12 tablets (3 g) of GABA and 3 tablets (600 mg) of pyrithioxine were given daily for 8 weeks. Subjective complaints, neurological and psychiatric findings, activity of daily living were checked at the 4th and 8th weeks after medication. The global improvement rates in GABA-treated groups were 59% and 70% each after 4 and 8 weeks of medication, and were significantly superior to the other two groups. Especially on cerebral arteriosclerosis GABA was more effective than the other two drugs, with statistical significance. As for improvement rates of symptoms there were significant differences between GABA and the other two drugs in subjective complaints and in psychiatric findings. The incidence of side effects was 5%, 20% and 8% in GABA, pyrithioxine and placebo, respectively. The incidence of abnormal laboratory data was 2% (3 cases), 8% (11 cases) and 4% (6 cases), respectively. Those in GABA group were transient and restored to normal values after the trial. It is concluded from these results that GABA is safe and effective in the treatment of cerebrovascular disorders.

Aged↗