Biomedical subjects
Publications and source records attributed to K Sakamoto.
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In order to assess the role of Epstein-Barr virus (EBV) in patients with hairy cell leukemia (HCL), we have sought to characterize 1) the ability of EBV to infect and transform hairy leukemic cells in vitro and 2) the phenotypes of cell lines putatively derived from those leukemic cells. Analysis of EBV-induced transformation and the kinetics of Epstein-Barr nuclear antigen (EBNA) induction in leukemic preparations indicated that most leukemic cells were not susceptible to EBV infection but that at least a small subpopulation of leukemic cells could be infected with EBV. Lymphoblastoid cells lines were established after exposure of peripheral blood or splenic cells from HCL patients to B95-8 or QIMR-WIL EBV. Splenic leukemic cell preparations were more sensitive targets for EBV transformation than were peripheral blood cell samples. The newly established cell lines, but not long-established B lines such as Raji, demonstrated high levels of synthesis of p35, (a protein complex expressed abundantly by cells of a subset of HCL patients) and high levels of tartrate-resistant acid phosphatase (an enzyme relatively diagnostic for HCL). Lymphoblastoid lines from one patient with HCL expressed lambda light chains and no kappa chains as did the patient's leukemic cells. Virus expression in these lines showed that HCL-derived lines had spontaneous early antigen (EA) and viral capsid antigen (VCA) expression. Transforming EBV could be rescued from HCL-derived cell lines but not from cord blood-derived lines.
Strong affinity of 167Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with 167Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of 167Tm. A large number of 167Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. 167Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of 167Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of 167Tm, hepatoma AH109A possessing some residual features of the liver. 167Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which 167Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate).
The case of a 17-year-old male who developed hypogammaglobulinemia following infectious mononucleosis is presented. The family history revealed that a male sibling had died some years earlier with encephalitis also following infectious mononucleosis. Laboratory investigations revealed adequate numbers of T and B cells and normal proportions of helper and suppressor T lymphocytes but poor in vitro responses to mitogens and an absence of hypersensitivity to skin test antigens. Serial serological examinations for Epstein-Barr virus antibodies indicated a primary immune response to this virus in a hypogammaglobulinemic individual. The patient probably represents a case of the X-linked lymphoproliferative syndrome. The unique feature of the present case is the demonstration of Epstein-Barr virus-specific T-cell memory. The significance of this finding and the variable expression of this syndrome in two members of the same family are discussed.
A case with multiple foci of signet-ring cell carcinoma in an adenoma of the rectum is presented. Four foci of the signet-ring cell carcinoma and four foci of the common type of adenocarcinoma were found independently in a large polypoid tumor. An originating point of one of the signet-ring cell cancer foci was shown by an extensive serial sectioning study.
In this paper, we discuss the problems of measurement of intra- and extra-cellular fluid distribution in living tissues by means of electrical impedance. The intra- and extra-cellular fluid distribution is related to some physiological parameters, such as blood circulation, metabolism of tissues, and the electrolytic concentration of intra- and extra-cellular fluids. Therefore, the information about the distribution of fluids in tissues is quite useful for the diagnosis of various diseases, the monitoring of seriously ill patients, and in medical treatments such as artificial dialysis. We discuss the method of measurement and the results of experiments.
Using HeLa S-100 extracts, we have transcribed total DNA isolated from several species of higher animals. Transcription of the total DNA from rat, mouse, or hamster gives a discrete product of 6S RNA (about 180 nucleotides) in addition to a smeared background, whereas transcription from chick, calf, or human DNA gives a discrete band of 5S RNA (about 120 nucleotides). In view of the sensitivity to a-amanitin, these transcripts are produced by RNA polymerase III. Fingerprint analysis demonstrated that the 6S RNA species transcribed from rodent DNA have conserved sequences. The composition of dinucleotides in these bands having a guanosine residue on the 3' side was analyzed by RNase T2 digestion. The results show that the CG ratios of the transcripts of rodent, calf and chick are quite low in comparison with AG, UG, or GG except in the case of the human transcript, suggesting that these highly repetitive transcribable sequences are derived from a common prototype sequence, except in human cells. We have isolated two phage clones and one phage clone from a rat and mouse genomic library, respectively, which give a transcript of 180 nucleotides in size, and whose pattern of RNase T2 digests is the same as that of the conserved transcriptional products of total DNA. These highly repetitive transcribable sequences appear to be reiterated at several to ten thousand copies per haploid genome. The relationship of these sequences with the highly repetitive interspersed sequence B1 or Alu family is discussed.
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Effects of moxibustion stimulation on the phagocytic activity of the reticuloendothelial system in ddY and ICR mice has been studied by using the carbon clearance methods. It was found that moxibustion stimulation induced the enhancement of the phagocytic activity with increased phagocytic indexes (K and a indexes) and lysosomal enzyme activities in mice peritoneal exudate cells and peritoneal macrophages. In addition, the increase of carbon uptake in the Kupffer cells of the liver after carbon injection can be seen by light microscopy when compared with that of nontreated mice. Few big holes on the cell surface of the macrophages obtained from the moxibustion mice were observed in scanning electron microscopical studies. These results suggest that the moxibustion treatment caused the enhancement of the host defence mechanisms in mice.
The relationship between the onset of hypertension and changes in monoamine oxidase (MAO) activity in the brains and hearts of spontaneously hypertensive rats (SHR) were studied. After 7-weeks-old, blood pressure of SHR increased rapidly and reached a level of 170 to 180 mmHg; but following 4 weeks of propranolol treatment (10 mg/kg/day), blood pressure decreased significantly compared to that of untreated SHR. Heart/body weights ratio of SHR was higher than that of normotensive Wistar Kyoto rats (WKY). MAO activities in the brain stem, the medulla oblongata and pons of the SHR were significantly higher than those in WKY at 7 weeks of age, and MAO activity in the brain stem of the propranolol-treated SHR was significantly lower than that in the untreated SHR. Propranolol inhibited MAO activity in brain tissue in vitro, and the I50 values of propranolol were identical (1 X 10(-4) M) in SHR and WKY. In both the WKY strain and the SHR, the Vmax values of heart MAO increased with age, and the Vmax values of SHR were twice those of WKY. Km values for tyramine of heart MAO in WKY and SHR were approx. 100 microM and 140 microM, respectively; however, these values were not age-dependent. It was concluded that an increase in MAO activity in SHR brain stem may trigger a reduction in noradrenaline content and that propranolol may be responsible for its restoration, thus reducing peripheral sympathetic activity; moreover, the increase in MAO activity in the hearts of SHR may be of genetic origin.
The effects of thiamine (T) on diabetes mellitus (DM) and the T levels in the brain, heart, liver, kidneys pancreas, muscle, adipose tissue and blood were measured. For the experimental DM model, alloxan (170 mg/kg, i.v.) was injected into male ddY mice and insulin was also administered for 5 days to prevent death by hyperglycemia (DM group). After 14 days, blood glucose level increased to 455 mg/dl, compared to 166 mg/dl in the normal control group (NC group). In the DM mice, the T level in the liver decreased to 7.71 micrograms/g, compared to 16.29 micrograms/g in the NC group. The T levels in the heart, pancreas, muscle and adipose tissue increased to 18.63 micrograms/g, 3.99 micrograms/g, 2.53 micrograms/g and 5.07 micrograms/g in the DM group, compared to 14.99 micrograms/g, 3.27 micrograms/g, 1.98 micrograms/g and 4.04 micrograms/g in the NC group, respectively. The T levels in the brain and kidney were 2.38 micrograms/g and 14.00 micrograms/g in the DM group, compared to 2.34 micrograms/g and 13.72 micrograms/g in the NC group, respectively. But, in the heart, an active form of a T co-enzyme decreased to 27%, compared to 95% for the NC group. These results indicate a T deficiency or an endogenous T deficiency in the DM group. All DM mice without insulin treatment died within 7 days but about 40% of the mice survived up to 14 days with the administration of T.
Experimental hyperlipidemia and atherosclerosis induced by a cholesterol diet in SPF male and female rabbits (JW/KBL) were investigated by the determination of the lipid contents of the plasma, liver and thoracic aorta; determination of morphological changes of the aortic arch by head angiography; and computer tomography of the brain. Rabbits were fed the diet that contained 1% cholesterol for eight weeks. The plasma lipid levels began to rise from two weeks after the cholesterol diet was started, reached the peak four to six weeks later, and then fell in both males and females at eight weeks. The cholesterol of the high density lipoprotein in male rabbit plasma was slightly increased by the cholesterol diet, but not in female rabbits. An increase in the total cholesterol (TC) and triglyceride contents of the liver and an increase in the TC and phospholipid contents of the thoracic aorta were observed at the eighth week. Histological examination of the aortic arch showed marked lipid vacuoles under the endothelial cells, noticeable lipid inclusions in the smooth muscle cells of the intima and granular prominences on the internal surface of the aorta. Head angiography of rabbits fed the cholesterol diet revealed a constriction of the lumina of several arteries due to the lipid depositions. These results suggest that hyperlipidemia and atherosclerosis can be produced at the eighth week using SPF rabbits fed on a cholesterol diet.
The isoelectric components of LH have been isolated from the male rat pituitary glands by preparative isoelectric focusing. The biological activities of these components were measured in vitro from testosterone production in rat Leydig cells at equal doses and expressed as the equivalent of NIH-LH-S1 immunoreactivity. There were significant differences in the bioactivities among the components. The bioactivities of the components decreased with decreasing pI; components E (pI = 9.6) and F (pI = 9.8) showed about 5- to 6-fold higher activities than component A' (pI = 7.9). When the rat pituitary extracts were measured for LH by radioimmunoassay, and then measured for the ratio of biological activity to immunoreactivity (B:I), the order was as follows; intact female rats greater than intact male rats greater than orchidectomized rats. This phenomenon could be explained by the differences in the relative amounts of the LH components which changed according to the physiological states. These observations indicate that the LH components with different pIs and B:I ratio are related to the different estimation of total LH in the rat pituitary glands by bioassay and radioimmunoassay.
Although mucolipidosis, a fatal metabolic storage disorder, is associated with cardiovascular abnormalities, detailed, non-invasive cardiac examinations have not been well documented. We studied 4 children with type II and type III mucolipidosis, 3 of whom had unequivocal evidence of aortic regurgitation characterized by phonocardiography and M-mode echocardiography. Two-dimensional echocardiography showed an aortic valve prolapse in 3, a mitral valve prolapse in 2 and a tricuspid valve prolapse in 1. The QT interval was prolonged in 2 cases. In 1 autopsy case, we found considerably thickened and retracted aortic, mitral, and tricuspid valves, and accumulation of the foam cells in the myocardium. Echocardiography revealed similar findings in another 3 cases. We conclude that cardiac manifestations in this disorder should be examined carefully particularly by the use of echocardiography which is an excellent technique for detecting cardiovascular abnormalities in mucolipidosis.
The incidence of vascular disorders was investigated in two groups of diabetics. One group (group-U) comprised 408 diabetics who were inhabitants of an urban district. The other group (group-R) consisted of 148 diabetics who were inhabitants of a rural district. The annual incidence rates of myocardial infarction and cerebrovascular disease in group-R were about twice as high as the respective rates in group-U. The prevalence rates of hypertension and ECG-abnormalities in group-R were also significantly higher than those in group-U (p less than 0.01). However, there was no appreciable difference between the two groups with respect to the incidence of proteinuria or proliferative retinopathy. Any significant difference between the two groups in age, obesity index, Hb-A1, T. Chol., TG. or HDL-C levels was not recognized. The duration of diabetes was relatively short in group-R. These findings suggest that the high incidence of myocardial infarction and cerebrovascular disease in group-R is not influenced by the difference in Hb-A1 or serum lipid levels, and that these vascular disorders are probably associated with hypertension and ECG-abnormalities.
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An alpha-fetoprotein (AFP)-producing human gastric carcinoma was transplanted into BALB/c-nu/nu nude mice. The original tumor tissue had been obtained by gastrectomy from a 72-year-old patient with gastric carcinoma. The tumor had been transplanted serially (20 passages) in nude mice. The transplantability was 100%. The doubling time of the tumor ranged from 5.6 days to 11.2 days. AFP appeared in the serum of nude mice 3 to 4 weeks after subcutaneous (sc) transplantation and 6 weeks after intraperitoneal (ip) transplantation of the tumor cell suspension prepared from sc transplanted tumors. A positive correlation was observed between serum AFP level and tumor size. Serum AFP level of mice given ip transplantation increased as a function of time after transplantation. AFP was stained positively by an immunochemical technique in the original and transplanted tumors and was located in the cytoplasms of the tumor cells. The histology of the original tumor was retained. The malignant potential of these transplanted tumor cells was expressed as carcinomatous peritonitis and liver and/or lung metastases.