[Experimental and clinical investigations on the method of analysis of hydroxyethyl starch and its absorption from the blood].
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Biomedical subjects
Publications and source records attributed to K Niimura.
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Infantile myofibromatosis (IM) is a proliferative disorder of infancy and early childhood characterized by the nodular or diffuse growth of lesions that are comprised of a mixture of mesenchymal elements. Intracranial involvement is reportedly rare, only eight such patients having been reported to our knowledge. We report on a 4-year-old boy with intracranial IM with a mass in his left temporal bone. A previous report on intracranial IM proposed that the underlying dura mater should be resected because of the possibility of early recurrence. At surgery in this case, the tumor was noted to be located in the bone itself and did not arise from the underlying dura. Therefore, the underlying dura mater and venous sinus were preserved. The follow-up MRI showed no sign of recurrences. It may not to be necessary to resect the dura mater in patients with intracranial IM.
K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G less than K18 less than melphalan. This activity of K18 was about half the theoretical value indicating that melphalan molecules are not released easily from the conjugate. K18 showed strong antitumour activity in vivo which continued after stopping administration. On the other hand, the effects of melphalan did not continue after administration was stopped. The distribution of [125I] K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.
K18 (3-[p-(N,N-bis(2'-chloroethyl)amino)- phenyl]-L-alanine conjugated with human immunoglobulin) is a newly developed antitumor agent. LD50 values of K18 in animals were quite high, suggesting its low acute toxicity. This drug showed anti-tumorigenicity not only on an experimental animal tumor (Walker 256), but also on a human tumor transplantable into nude mice (RCC-13). A distribution study clarified the unique properties of K18 to accumulate and remain in the tumor site with a high rate.
K18 is a newly synthesized antitumor agent which is the conjugate form of human immunoglobulin with p-di (2-chloroethyl)-amino-L-phenylalamine (melphalan). The antitumor effect of K18 on two animal metastatic models was investigated: (a) Lewis lung carcinoma was transplanted into thigh muscle of mice, followed by the reaction of the primary lesion, or the tumor was transplanted through the tail vein: (b) a renal model was also created, where colon-26 was inoculated into the renal capsule of BALB/c mice. Oral administration of K18 resulted in the decrease in the number of nodules in the lung in the case of tumor transplantation through tail vein.
IgG of normal female ICR mice was obtained and covalently conjugated with an alkylating agent, melphalan. The conjugate exhibited marked antitumor activities against Sarcoma 180 and Erhlich carcinoma cells inoculated subcutaneously into ICR mice. Based upon this experiment, melphalan was conjugated with human IgG. Antitumor activities of the conjugate, named K18, were tested against a variety of murine tumor cell lines in vivo. Additionally, K18 was tested in vivo against MX-1, MK-2 and LC-10 human tumor cell lines (of the breast, stomach, and lung respectively). The results showed antineoplastic activities on both murine and human tumor cell lines, thus indicating a possible new antitumor agent.
The binding and tissue distribution of 125I-labeled rabbit anti-sarcoma 180 (S-180) immunoglobulin G (IgG) (RAS-180G), normal rabbit IgG (NRG) and ICR mouse IgGs from normal (NMG) and S-180-bearing ICR mice (AS-180G) were studied in ICR mice bearing S-180. 125I-labelled IgGs preparted from normal (NC57G) or Adenocarconoma 755 (Ca 755)-bearing C57BL/6 mice (A755G) were also examined in C57BL/6 mice bearing ca755. Not only RAS-180G and AS-180G but also NRG and NMG persisted in the tumor site. This result suggests that allogeneic natural IgG could be used as a carrier protein for antitumor agents.