[The choice of plasma substitutes and methods of their application].
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Biomedical subjects
Publications and source records attributed to T Tani.
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In order to improve the response rate of chemotherapy, we have investigated to the method for rapid and accurate prediction of the most appropriate anticancer agents. Thus, a rapid method using nude mice has been established as in vivo model for assessing chemosensitivity of individual human tumors, in which the final evaluation was made with 3H-thymidine incorporation and histological changes of tumor cells treated. Correlation between the sensitivity of anticancer agents and retrospective results of gastrectomy in stage IV gastric cancer was investigated. Our sensitivity test indicated a good correlation with clinical therapeutic and immunological effects. From these results, it seems reasonable to conclude that the sensitivity test using human tumor/nude mouse system may be useful for selection of appropriate agents to treat patients with cancer.
Since interferon (IFN) has a mechanism of action very different from chemotherapeutic agents, it is possible that a combination of two may be of therapeutic value. The authors studied increased cytotoxic effects of anticancer drugs by IFN on human tumors xenografts in nude mice. Tumor used in this study were "SH-10", "S-7379" (gastric cancer) and "O-7294" (malignant melanoma), serially transplanted subcutaneously. IFN was injected, 5 X 10(5) mu/mouse, every day for 2 weeks and a single drug was administered 3 times every fourth day. Cytotoxic effect was determined by tumor size on day 16 after treatment. Of the 7 drugs, MMC and ADM were most effective. Other drugs showed a slight inhibition of tumor growth by combination therapy with drugs and IFN.
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Six phage clones that contain sequences hybridizable with the small nuclear RNA U2 were isolated from a rat gene library. Of these clones, one which includes a candidate for a functional U2 RNA gene was selected and characterized. The sequence within the clone which hybridizes with rat U2 RNA was completely co-linear with that of the RNA. A T-A-T-A box was not found in the region of more than 400 base-pairs which lies upstream of the gene. However, several block homologies were found with the upstream sequences of a rat U1 RNA gene candidate cloned in our laboratory. An "identifier sequence", which was reported to be an element of gene regulation related to differentiation, was found downstream of the coding region at the same distance and with the same orientation as the identifier sequence located downstream of the U1 RNA gene candidate. We detected a presumed U2 RNA precursor elongated by about 11 nucleotides at the 3' end by S1 nuclease mapping using a fragment from the clone. A potential termination signal for transcription was found within the elongated region of the presumed precursor. Southern blot analysis suggests that families of U2 RNA genes that have conserved flanking sequences are present in the genomes of rat, mouse, man, calf and chicken.
Four phage clones which hybridize with U1 small nuclear RNA were obtained from a rat gene library. Two clones contain a presumed pseudogene. A third clone includes two gene candidates that are co-linear with the rat U1-RNA, 3.6kb apart and in the opposite orientation. The two genes are surrounded by identical sequences of 491bp upstream and 178bp downstream. The upstream sequences do not contain a TATA box, but share many block homologies with those for the human U1-RNA gene(1-3). A 101bp "identifier (ID) sequence", which was reported to be specifically expressed in rat brain (4), is inserted immediately after the shared sequence downstream of one of the genes. In the fourth clone, there are two putative pseudogenes, which have one or three nucleotide changes, 3kb apart and in the same orientation. Southern blot analysis of total rat DNA reveals about 50 U1-RNA genes/pseudogenes in the genome.
An extremely rare case of bilateral oblique facial cleft is presented. This should be classified as a bilateral oroocular Type I cleft according to Boo-Chai's classification and a bilateral No. 4 cleft according to Tessier's classification. Except for this deformity, the patient was normal and healthy. Corrective surgical procedures were carried out between the ages of 4 months and 18 months to repair the left and right clefts, remove an abscess caused by the remnant of the lacrimal canal, and repair the cleft palate. The patient is now making a good recovery. Bone graftings or craniofacial osteotomies may be recommended at a later age.
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In an attempt to elucidate whether assessment of the brainstem function helps to predict the outcome of early idiopathic scoliosis, a series of neurophysiological studies in children with idiopathic scoliosis was made cooperatively in Japan and the United States. The eye movement in 86 cases with idiopathic scoliosis in the rapidly growing ages was tested and compared with 66 normal control children. About one-half of the patients with idiopathic scoliosis demonstrated dysfunction in the brainstem test. The natural histories of the curves were available in 48 of the 86 cases in a follow-up study ranging from 6 months to 2 1/2 years. Statistically, there was a positive correlation between the brainstem dysfunction and the curve progression. It was concluded that the functional assessment of the brain center of the postural regulation system can be used in predicting the outcome of idiopathic early curves detected in the school screening program.
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Pharmacological properties of buprenorphine were compared with those of morphine and pentazocine. Buprenorphine scarcely showed any effects on spontaneous EEGs and sleep-wakefulness cycles. Buprenorphine tended to depress the recruiting and augmenting responses and the spindle burst, and it also inhibited the hypothalamic arousal response. Buprenorphine had weaker emetic action than morphine and protected against apomorphine-induced emesis in the same manner as morphine. Buprenorphine scarcely affected respirations, blood pressure, heart rate, blood flow, ECG, cardiac contractile force, cornary flow, and intracranial pressure. However, morphine and pentazocine caused depressed respiration, decreased blood pressure, increased blood flow and cardiac contractile force, and elevated intracranial pressure. Buprenorphine, morphine, and pentazocine did not affect bile secretion, but produced contraction of the sphincter of Oddi. Buprenorphine had very little effect on renal function, but morphine and pentazocine reduced this function to depress urine flow. Buprenorphine and morphine inhibited carrageenin-induced edema. Buprenorphine had no effect on blood histamine level, but morphine increased the concentration of histamine. These results indicate that buprenorphine has little effect on the central nervous system, respiratory and cardiovascular system, and renal function.
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We have isolated four clones which hybridize with U6 (4.8S) nuclear RNA, a mammalian small nuclear RNA(nRNA), from DNA of BALB/C mouse liver. Their restriction maps are totally different from each other, indicating that they derived from different loci in the mouse genome. The nucleotide sequences around the hybridizing region in the three clones have been determined. One clone gives a gene that is co-linear with the U6 RNA. There is a sequence TATAAAT beginning 31 nucleotides upstream of the gene, which may suggest that the U6 RNA is transcribed by RNA polymerase II. The other two clones contain a pseudogene for the U6 RNA which has 7 or 9 nucleotide changes from the RNA. The pseudogenes are surrounded by radically different sequences from those surrounding the gene, and they are closely linked to a pseudogene for another snRNA, 4.5S-I RNA, or a part of highly repetitive an interspersed sequence B1.
In the chemotherapy for gastric cancer, the most sensitive anticancer agent against individual tumors should be prescribed. The establishment of a sensitivity test using nude mice as an in vivo model is urgently awaited by clinicians and researchers alike. Seventy-three tumors derived from human gastric cancer were transplanted subcutaneously into nude mice and these mice were then treated intraperitoneally with anticancer agents. Mitomycin C (MMC), 5-fluorouracil (5-FU) and cyclophosphamide (CPM) were used. The doses given were 3 mg/kg of MMC, 75 mg/kg of 5-FU and 200 mg/kg of CPM. IN 52 of the 73 cancers, chemosensitivity was evaluated by the microscopic changes in the tumors. The rate of positive sensitivity against gastric cancer was 42.2% in MMC, 34.6% in 5-FU and 30.8% in CPM, respectively. The sensitivity of each agent tested by this method indicated a good correlation with the clinical therapeutic effects. Our results suggest the feasibility of evaluation of the sensitivity of various agents from the microscopic changes on tumors transplanted into nude mice.
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