Biomedical subjects
Publications and source records attributed to K Sakamoto.
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Cancer grows in interaction with the host, that is, a host-tumor relationship exists. Investigations of host factors in patients receiving cancer chemotherapy are important, as they reveal the conditions in which a tumor response can develop. Furthermore, reliable host factors, if present, will be useful for quantitative evaluation of the effects of treatment. We have investigated the following three categories of host factors in relation to the effects of cancer chemotherapy and/or immunotherapy. CBC, and blood chemistries (44 parameters). Tumor markers; sialic acid, RNase, lysozyme, ferritin, IAP (immunosuppressive acidic protein), elastase I, AFP, CEA, POA, CA 19-9, CA 125, etc. Immunological parameters; lymphocyte, active T cell, T cell, B cell, IgG Fc receptor-positive T cell, lymphocyte blastogenesis stimulated by PHA, or concanavalin-A, ADCC activity, interferon production in vitro induced by poly I: C, or PHA, PPD skin test, immune complex, immunoglobulin G, A, and M, OKT series 3, 4, 8, 11, 4/8 ratio, antihuman HLA-DR, Leu 11, NK cell activity, etc. From our clinical observations, there were no significant differences in the pretreatment levels of these parameters between responders and non-responders. In responders, there was a tendency for the host factors to show greater degrees of improvement following treatment than in non-responders, but none proved to be reasonably reliable parameters for evaluating therapeutic effects. On the other hand, from our clinical observations on the advanced gastric cancer cases, life span showed a close correlation with tumor regression induced by cancer chemotherapy. Because of these facts, it is only natural that the clinical effects of chemotherapy are currently determined by definite tumor regression.
We report a case of intrahepatic lithiasis associated with intestinal malrotation, which showed some bile duct abnormalities, such as cystic dilatation accompanied with stenosis in its distal portion. The resected hepatic tissue was examined histopathologically. Cellular debris due to desquamation of the epithelium, hypersecretion of mucopolysaccharides from the proliferated intrahepatic glands, and periductal laminar or band-like fibrosis were present. The mixture of desquamated epithelium, mucopolysaccharides and bile juice occupied the bile duct lumen, suggesting intrahepatic immature gallstones. The timing of formation of the intrahepatic bile duct is nearly coincident with that of the rotation of the intestine. Intestinal malrotation is sometimes associated with the congenital biliary duct anomaly and therefore the present patient might were well be the case.
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Previous studies showed that the rat identifier sequence, the rodent type 2 Alu family, the rabbit C family and the bovine or goat 73 bp repeat show remarkable resemblance with a few specific tRNA molecules (Sakamoto and Okada, J. Mol. Evol. in press). This paper reports 5-methylcytidylic modification of the in vitro transcript from the ID sequence, and provides further evidence that the transcript forms a tRNA-like structure in vitro. Fingerprint analysis and oligonucleotide mapping suggested that the sequence of the oligonucleotide containing 5-methylcytidine is CpCpm5CpUpGp, which corresponds to the extra and T psi stem regions in the secondary structure of phenylalanine tRNA. Since the sequence of the corresponding oligonucleotide in the phenylalanine tRNA is Cpm5CpCpUpGp, these results suggests that a tRNA (cytosine-5) methyl transferase recognizes the secondary structure of the transcript from the ID sequence rather than the primary sequence. The significance of this modification in relation to the functional role of the ID sequence is discussed.
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The effect of cyanide on 7-ethoxycoumarin O-deethylation by two cytochrome P-450 isozymes obtained from 3-methylcholanthrene treated rat liver microsomes was investigated. 7-Ethoxycoumarin O-deethylation was stimulated by the addition of cyanide to a reconstituted monooxygenase system consisting of NADPH, dilauroyl 3-L-phosphatidylcholine, NADPH-cytochrome P-450 reductase and MC P-448(2) (low spin form of cytochrome). In contrast, a weak inhibitory effect of cyanide on 7-ethoxycoumarin O-deethylation was observed when MC P-448(1) (high spin form of cytochrome) was used in the reconstituted system. Cyanide did not influence the apparent Km for 7-ethoxycoumarin when either form of cytochrome P-450 was used in the reconstituted system and did not stimulate the cumene hydroperoxide dependent O-deethylation by MC P-448(2). The stimulatory effect of cyanide on O-deethylation by MC P-448(2) was decreased with increasing the concentration of the reductase added to the reconstituted system. On the other hand, the effect of cyanide on O-deethylation by MC P-448(1) was virtually independent on the amount of the reductase added.
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A case of arteriovenous malformation (AVM) of the cervical spinal cord occurring in a 17-month-old girl is reported. The initial symptom was quadriplegia of abrupt onset. Bilateral vertebral angiography disclosed 6 feeding arteries and a large draining vein. Complete obstruction of the blood supply to the AVM was confirmed angiographically, following cauterization and section of feeders via an anterior approach. Two years after the operation, the patient can sit and move all extremities with residual slight right hemiparesis. This report is the first operative case of cervical cord AVM in a child under 2 years of age.
2,8-Dihydroxyadenine urolithiasis associated with partial deficiencies of adenine phosphoribosyltransferase (APRT) has been found only among Japanese families. All Caucasian patients with the same lithiasis are completely deficient in this enzyme. Partially purified APRT from one of the Japanese families with the lithiasis associated with a partial deficiency of APRT had a reduced affinity for 5-phosphoribosyl-1-pyrophosphate (PRPP). In the present investigations, we have shown that this characteristic is common in mutant enzymes from all the four separate Japanese urolithiasis families associated with partial APRT deficiencies so far tested. The mutant enzymes also had several other characteristics in common including increased resistance to heat in the absence of PRPP and reduced sensitivity to the stabilizing effect of PRPP. These data suggest that these families have a common mutant allele (APRT*J) at the APRT gene locus.
Close structural resemblances between several mammalian highly or moderately repetitive families and some specific tRNAs were detected. The rodent type 2 Alu family, rat identifier (ID) sequences, rabbit C family, and bovine or goat 73-bp repeat are most homologous with lysine tRNA5, phenylalanine tRNA, glycine tRNA, and glycine tRNA, respectively. The homologies extend to secondary structures, and the homologous nucleotides are located on nearly the same secondary structures. The repetitive families mentioned have a common structural organization, with a tRNA-like sequence devoid of an aminoacyl stem region. These features suggest that these repetitive families may be generated by nonhomologous recombination between a tRNA gene and a tRNA-unrelated block.
We carried out studies to determine whether the Tritiated Thymidine Labeling Index (TLI) would correlate with hormone receptors as well as with clinical and histological data. Sixty-four patients with breast cancer were the subjects studied. TLI showed no relationship to age, menopausal status, T-factor, n-factor, stage, or histological type. However, compared to tubule formation, nuclear pleomorphism, and mitotic activity, TLI showed a positive correlation with each and accordingly there was a positive correlation between TLI and Bloom's histological grading. The cumulative disease-free rate at three years was higher in case of a TLI below 4.0 (median TLI value). TLI significantly correlated inversely with the binding sites not only of cytoplasmic estrogen receptors (ERC), but also of cytoplasmic progesterone receptors (PRC) and nuclear estrogen receptors (ERN). Cancers negative for all three receptors indicated the highest TLI, while cancers positive for all three receptors showed the lowest TLI. The results suggest that breast cancers positive for hormone receptors were of low malignancy because lower TLI related to a lower proliferative activity. Thus, TLI is an useful parameter for assessing the clinical status of breast cancers.
This study was carried out to determine whether hormone receptors and the Tritiated Thymidine Labeling Index (TLI) would change with intervening treatment in 7,12-dimethylbenz(a)anthracen-induced rat mammary cancer as well as to evaluate their predictive significance. Forty-eight tumors were studied. TLI significantly correlated inversely with the binding sites of cytoplasmic estrogen receptors (ERC), but not of cytoplasmic progesterone receptors (PRC). From the response to the two treatments ovariectomy or adriamycin, it was demonstrated that ERC was a predictor of the response to ovariectomy and TLI showed a predictive value in the response to adriamycin. Ovariectomy generally induced a marked decrease in ERC level and PRC level, whereas adriamycin led to an increase and decrease in ERC level and PRC level, respectively. TLI showed a remarkable decrease in tumors which were responsive to ovariectomy or adriamycin. Some tumors, which had been the intermediate or ineffective group with a previously given treatment, were evaluated for the first time as being the effective group with another type of treatment. These results suggest that the response to treatment for breast cancer may change over the clinical course and ideal treatment for advanced breast cancer should included concomitant chemo-endocrine therapy.
One hundred and eighty-five inpatients with ulcer in the gastric corpus and angle were treated with either 1 g cimetidine per day or with a combination of antacid and anticholinergic. At 2, 4, 6 and 8 weeks after entry into the study, the ulcer had healed in 3.3, 30.4, 55.4 and 87.0 per cent of patients treated with cimetidine, as compared with 0, 12.9, 51.6 and 73.1 per cent of those treated with a combination of antacid and anticholinergic (NS., p less than 0.01, NS., p less than 0.05), respectively. Factors that had a delaying effect on ulcer healing were seen more frequently in the cimetidine group. Thus, cimetidine proved to be superior to a combination of antacid and anticholinergic, for the treatment of gastric ulcer.